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Shaping the Future of Science: 2019 Blavatnik Science Symposium

Overview

The New York Academy of Sciences and the Blavatnik Family Foundation hosted the annual Blavatnik Science Symposium on July 15–16, 2019, uniting 75 Finalists, Laureates, and Winners of the Blavatnik Awards for Young Scientists. Honorees from the UK and Israel Awards programs joined Blavatnik National and Regional Awards honorees from the U.S. for what one speaker described as “two days of the impossible.” Nearly 30 presenters delivered research updates over the course of nine themed sessions, offering a fast-paced peek into the latest developments in materials science, quantum optics, sustainable technologies, neuroscience, chemical biology, and biomedicine.

Symposium Highlights

  • Computer vision and machine learning have enabled novel analyses of satellite and drone images of wildlife, food crops, and the Earth itself. 
  • Next-generation atomic clocks can be used to study interactions between particles in complex many-body systems.
  • Bacterial communities colonizing the intestinal tract produce bioactive molecules that interact with the human genome and may influence disease susceptibility.
  • New catalysts can reduce carbon emissions associated with industrial chemical production.
  • Retinal neurons display a surprising degree of plasticity, changing their coding in response to repetitive stimuli.
  • New approaches for applying machine learning to complex datasets is improving predictive algorithms in fields ranging from consumer marketing to healthcare.
  • Breakthroughs in materials science have resulted in materials with remarkable strength and responsiveness.
  • Single-cell genomic studies are revealing some of the mechanisms that drive cancer development, metastasis, and resistance to treatment.

Speakers

Emily Balskus, PhD
Harvard University

Chiara Daraio, PhD
Caltech

William Dichtel, PhD Northwestern University

Elza Erkip, PhD
New York University

Lucia Gualtieri, PhD
Stanford University

Ive Hermans, PhD
University of Wisconsin – Madison

Liangbing Hu, PhD
University of Maryland, College Park

Jure Leskovec, PhD
Stanford University

Heather J. Lynch, PhD
Stony Brook University

Wei Min, PhD
Columbia University

Seth Murray, PhD
Texas A & M University

Nicholas Navin, PhD, MD
MD Anderson Cancer Center

Ana Maria Rey, PhD
University of Colorado Boulder

Michal Rivlin, PhD
Weizmann Institute of Science

Nieng Yan, PhD
Princeton University

Event Sponsor

Technology for Sustainability

Speakers

Heather J. Lynch
Stony Brook University

Lucia Gualtieri
Stanford University

Seth Murray
Texas A & M University

Highlights

  • Machine learning algorithms trained to analyze satellite imagery have led to the discovery of previously unknown colonies of Antarctic penguins.
  • Seismographic data can be used to analyze more than just earthquakes—typhoons, hurricanes, iceberg-calving events and landslides are reflected in the seismic record.
  • Unmanned aerial systems are a valuable tool for phenotypic analysis in plant breeding, allowing researchers to take frequent measurements of key metrics during the growing season and identify spectral signatures of crop yield.

Satellites, Drones, and New Insights into Penguin Biogeography

Satellite images have been used for decades to document geological changes and environmental disasters, but ecologist and 2019 Blavatnik National Awards Laureate in Life Sciences, Heather Lynch, is one of the few to probe the database in search of penguin guano. She opened the symposium with the story of how the Landsat satellite program enabled a surprise discovery of several of Earth’s largest colonies of Adélie penguins, a finding that has ushered in a new era of insight into these iconic Antarctic animals.

Steady streams of high quality spatial and temporal data regularly support environmental science. In contrast, Lynch noted that wildlife biology has advanced so slowly that many field techniques “would be familiar to Darwin.” Collecting information on animal populations, including changes in population size or migration patterns, relies on arduous and imprecise counting methods. The quest for alternative ways to track wildlife populations—in this case, Antarctic penguin colonies—led Lynch to develop a machine learning algorithm for automated identification of penguin guano in high resolution commercial satellite imagery, which can be combined with lower resolution imagery like that coming from NASA’s Landsat program. Pairing measurements of vast, visible tracts of penguin guano—the excrement colored bright pink due to the birds’ diet—with information about penguin colony density yields near-precise population information. The technique has been used to survey populations in known penguin colonies and enabled the unexpected discovery of a “major biological hotspot” in the Danger Islands, on the tip of the Antarctic Peninsula. This Antarctic Archipelago is so small that it is doesn’t appear on most maps of the Antarctic continent, yet it hosts one of the world’s largest Adélie penguin hotspots.

Satellite images of the pink stains of Antarctic penguin guano have been used to identify and track penguin populations.

Lynch and her colleagues are developing new algorithms that utilize high-resolution drone and satellite imagery to create centimeter-scale, 3D models of penguin terrain. These models feed into detailed habitat suitability and population-tracking analyses that further basic research and can even influence environmental policy decisions. Lynch noted that the discovery of the Danger Island colony led to the institution of crucial environmental protections for this region that may have otherwise been overlooked.  “Better technology actually can lead to better conservation,” she said.

Listening to the Environment with Seismic Waves

The study of earthquakes has dominated seismology for decades, but new analyses of seismic wave activity are broadening the field. “The Earth is never at rest,” said Lucia Gualtieri, 2018 Blavatnik Regional Awards Finalist, while reviewing a series of non-earthquake seismograms that show constant, low-level vibrations within the Earth. Long discarded as “seismic noise,” these data, which comprise more than 90% of seismograms, are now considered a powerful tool for uniting seismology, atmospheric science, and oceanography to produce a holistic picture of the interactions between the solid Earth and other systems.

In addition to earthquakes, events such as hurricanes, typhoons, and landslides are reflected in the seismic record.

Nearly every environmental process generates seismic waves. Hurricanes, typhoons, and landslides have distinct vibrational patterns, as do changes in river flow during monsoons and “glacial earthquakes” caused by ice calving events. Gualtieri illustrated how events on the surface of the Earth are reflected within the seismic record—even at remarkably long distances—including a massive landslide in Alaska detected by a seismic sensor in Massachusetts. Gualtieri and her collaborators are tapping this exquisite sensitivity to create a new generation of tools capable of measuring the precise path and strength of hurricanes and tropical cyclones, and for making predictive models of cyclone strength and behavior based on decades of seismic data.

Improving Crop Yield Using Unmanned Aerial Systems and Field Phenomics

Plant breeders like Seth Murray, 2019 Blavatnik National Awards Finalist, are uniquely attuned to the demands a soaring global population places on the planet’s food supply. Staple crop yields have skyrocketed thanks to a century of advances in breeding and improved management practices, but the pressure is on to create new strategies for boosting yield while reducing agricultural inputs. “We need to grow more plants, measure them better, use more genetic diversity, and create more seasons per year,” Murray said. It’s a tall order, but one that he and a transdisciplinary group of collaborators are tackling with the help of a fleet of unmanned aerial systems (UAS), or drones.

Drones facilitate frequent measurement of plant height, revealing variations between varietals early in the growth process.

Genomics has transformed many aspects of plant breeding, but phenotypic, rather than genotypic, information is more useful for predicting crop yield. Using drones equipped with specialized equipment, Murray has not only automated many of the time-consuming measurements critical for plant phenotyping, such as tracking height, but has also identified novel metrics that can accelerate the development of new varietals. Spectral signatures obtained via drone can be used to identify top-yielding varietals of maize even before the plants are fully mature. Phenotypic features distilled from drone images are also being used to determine attributes such as disease resistance, which directly influence crop management. Murray’s team is modeling the influence of thousands of phenotypes on overall crop performance, paving the way for true phenomic selection in plant breeding.

Further Readings

Lynch

Borowicz A, McDowall P, Youngflesh C, et al.

Multi-modal survey of Adélie penguin mega-colonies reveals the Danger Islands as a seabird hotspot.

Sci Rep. 2018 Mar 2;8(1):3926.

Che-Castaldo C, Jenouvrier S, Youngflesh C, et al.

Pan-Antarctic analysis aggregating spatial estimates of Adélie penguin abundance reveals robust dynamics despite stochastic noise.

Nat Commun. 2017 Oct 10;8(1):832.

Murray

Zhang M, Cui Y, Liu YH, et al.

Accurate prediction of maize grain yield using its contributing genes for gene-based breeding.

Genomics. 2019 Feb 28. pii: S0888-7543(18)30708-0.

Shi Y, Thomasson JA, Murray SC, et al.

Unmanned Aerial Vehicles for High-Throughput Phenotyping and Agronomic Research.

PLoS One. 2016 Jul 29;11(7):e0159781.

Quantum Optics

Speakers

Ana Maria Rey
University of Colorado Boulder

Highlights

  • Quantum mechanics underlies the technologies of modern computing, including transistors and integrated circuits.
  • Most quantum insights are derived from studies of single quantum particles, but understanding interactions between many particles is necessary for the development of devices such as quantum computers.
  • Atoms cooled to one billionth of a degree above absolute zero obey the laws of quantum mechanics, and can be used as quantum simulators to study many-particle interactions.

Atomic Clocks: From Timekeepers to Quantum Computers

The discovery of quantum mechanics opened “a new chapter in human knowledge,” said 2019 Blavatnik National Awards Laureate in Physical Sciences & Engineering, Ana Maria Rey, describing how the study of quantum phenomena has revolutionized modern computing, telecommunications, and navigation systems. Transistors, which make up integrated circuits, and lasers, which are the foundation of the atomic clocks that maintain the precision of satellites used in global positioning systems, all stem from discoveries about the nature of quantum particles.

The next generation of innovations—such as room temperature superconductors and quantum computers—will be based on new quantum insights, and all of this hinges on our ability to study interactions between many particles in quantum systems. The complexity of this task is beyond the scope of even the most powerful supercomputers. As Rey explained, calculating the possible states for a small number of quantum particles (six, for example) is simple. “But if you increase that by a factor of just 10, you end up with a number of states larger than the number of stars in the known universe,” she said.

Calculating the number of possible states for even a small number of quantum particles is a task too complex for even the most powerful supercomputer.

Researchers have developed several experimental platforms to clear this hurdle and explore the quantum world. Rey shared the story of how her work developing ultra-precise atomic clocks inadvertently led to one experimental platform that is already demystifying some aspects of quantum systems.

Atomic clocks keep time by measuring oscillations of atoms—typically in cesium atoms—as they change energy levels. Recently, Rey and her collaborators at JILA built the world’s most sensitive atomic clock using strontium atoms instead of cesium and using many more atoms that are typically found in these clocks. The instrument had the potential to be 1,000 times more sensitive than its predecessors, yet collisions between the atoms compromised its precision. Rey explained that by suppressing these collisions, their clock became “a window to explore the quantum world.” Within this framework, the atoms can be manipulated to simulate the movement and interactions of quantum particles in solid-state materials. Rey reported that this clock-turned-quantum simulator has already generated new findings about phenomena including superconductivity and quantum magnetism.

Further Readings

Rey

Goban A, Hutson R, Marti GE, et al.

Emergence of multi-body interactions in a fermionic lattice clock.

Nature. 2018 Nov;563(7731):369-373.

Kolkowitz S, Bromley SL, Bothwell T, et al.

Spin-orbit-coupled fermions in an optical lattice clock.

Nature. 2017 Feb 2;542(7639):66-70.

Chemical Biology

Speakers

Emily Balskus
Harvard University

Highlights

  • The human gut is colonized by trillions of bacteria that are critical for host health, yet may also be implicated in the development of diseases including colorectal cancer.
  • For over a decade, chemists have sought to resolve the structure of a genotoxin called colibactin, which is produced by a strain of E. coli commonly found in the gut microbiome of colorectal cancer patients.
  • By studying the specific type of DNA damage caused by colibactin, researchers found a trail of clues that led to a promising candidate structure of the colibactin molecule.

Gut Reactions: Understanding the Chemistry of the Human Gut Microbiome

The composition of the trillions-strong microbial communities that colonize the mammalian intestinal tract is well characterized, but a deeper understanding of their chemistry remains elusive. Emily Balskus, the 2019 Blavatnik National Awards Laureate in Chemistry, described her lab’s hunt for clues to solve one chemical mystery of the gut microbiome—a mission that could have implications for colorectal cancer (CRC) screening and early detection.

Some commensal E. coli strains in the human gut produce a genotoxin called colibactin. When cultured with human cells, these strains cause cell cycle arrest and DNA damage, and studies have shown increased populations of colibactin-producing E. coli in CRC patients. Previous studies have localized production of colibactin within the E. coli genome and hypothesized that the toxin is synthesized through an enzymatic assembly line. Yet every attempt to isolate colibactin and determine its chemical structure had failed.

Balskus’ group took “a very different approach,” in their efforts to discover colibactin’s structure. By studying the enzymes that make the toxin, the team uncovered a critical clue: a cyclopropane ring in the structure of a series of molecules they believed could be colibactin precursors. This functional group, when present in other molecules, is known to damage DNA, and its detection in the molecular products of the colibactin assembly line led the researchers to consider it as a potential mechanism of colibactin’s genotoxicity.

In collaboration with researchers at the University of Minnesota School of Public Health, Balskus’ team cultured human cells with colibactin-producing E. coli strains as well as strains that cannot produce the toxin. They identified and characterized the products of colibactin-mediated DNA damage. “Starting from the chemical structure of these DNA adducts, we can work backwards and think about potential routes for their production,” Balskus explained.

A proposed structure for the genotoxin colibactin, which is associated with colorectal cancer, features two cyclopropane rings capable of interacting with DNA to generate interstrand cross links, a type of DNA damage.

Further studies revealed that colibactin triggers a specific type of DNA damage that requires two reactive groups—likely represented by two cyclopropane rings in the final toxin structure—a pivotal discovery in deriving what Balskus believes is a strong candidate for the true colibactin structure. Balskus emphasized that this work could illuminate the role of colibactin in carcinogenesis, and may lead to cancer screening methods that rely on detecting DNA damage before cells become malignant. The findings also have implications for understanding microbiome-host interactions. “These studies reveal that human gut microbiota can interact with our genomes, compromising their integrity,” she said.

Further Readings

Balskus

Jiang Y, Stornetta A, Villalta PW et al.

Reactivity of an Unusual Amidase May Explain Colibactin’s DNA Cross-Linking Activity.

J Am Chem Soc. 2019 Jul 24;141(29):11489-11496.

Wilson MR, Jiang Y, Villalta PW, et al.

The human gut bacterial genotoxin colibactin alkylates DNA.

Science. 2019 Feb 15;363(6428).

Synthetic Methodology

Speakers

Ive Hermans
University of Wisconsin – Madison

William Dichtel
Northwestern University

Highlights

  • The chemical industry is a major producer of carbon dioxide, and efforts to create more efficient and sustainable chemical processes are often stymied by cost or scale.
  • Boron nitride is not well known as a catalyst, yet experiments show it is highly efficient at converting propane to propylene—one of the most widely used chemical building blocks in the world.
  • Two-dimensional polymers called covalent organic frameworks (COFs) can be used for water filtration, energy storage, and chemical sensing.
  • Until recently, researchers have struggled to control and direct COF formation, but new approaches to COF synthesis are advancing the field.

Boron Nitride: A Surprising Catalyst

Industrial chemicals “define our standard of living,” said Ive Hermans, 2019 Blavatnik National Awards Finalist, before explaining that nearly 96% of the products used in daily life arise from processes requiring bulk chemical production. These building block molecules are produced at an astonishingly large scale, using energy-intensive methods that also produce waste products, including carbon dioxide.

Despite pressure to reduce carbon emissions, the pace of innovation in chemical production is slow. The industry is capital-intensive — a chemical production plant can cost more than $2 billion—and it can take a decade or more to develop new methods of synthesizing chemicals.  Concepts that show promise in the lab often fail at scale or are too costly to make the transition from lab to plant. “The goal is to come up with technologies that are both easily implemented and scalable,” Hermans said.

Catalysts are a key area of interest for improving chemical production processes. These molecules bind to reactants and can boost the speed and efficiency of chemical reactions. Hermans’ research focuses on catalyst design, and one of his recent discoveries, made “just by luck,” stands to transform production of one of the most in-demand chemicals worldwide—propylene.

Historically, propylene was one product (along with ethylene and several others) produced by “cracking” carbon–carbon bonds in naphtha, a crude oil component that has since been replaced by ethane (from natural gas) as a preferred starting material. However, ethane yields far less propylene, leaving manufacturers and researchers to seek alternative methods of producing the chemical.

Boron nitride catalyzes a highly efficient conversion of propane to propylene.

Enter boron nitride, a two-dimensional material whose catalytic properties took Hermans by surprise when a student in his lab discovered its efficiency at converting propane, also a component of natural gas, to propylene. Existing methods for running this reaction are endothermic and produce significant CO2. Boron nitride catalysts facilitate an exothermic reaction that can be conducted at far cooler temperatures, with little CO2 production. Better still, the only significant byproduct is ethylene, an in-demand commodity.

Hermans sees this success as a step toward a more sustainable future, where chemical production moves “away from a linear economy approach, where we make things and produce CO2 as a byproduct, and more toward a circular economy where we use different starting materials and convert CO2 back into chemical building blocks.”

Polymerization in Two Dimensions

William Dichtel, a Blavatnik National Awards Finalist in 2017 and 2019, offered an update from one of the most exciting frontiers in polymer chemistry—two-dimensional polymerization. The synthetic polymers that dominate modern life are comprised of linear, repeating chains of linked building blocks that imbue materials with specific properties. Designing non-linear polymer architectures requires the ability to precisely control the placement of components, a feat that has challenged chemists for a decade.

Dichtel described the potential of a class of polymers called covalent organic frameworks, or COFs—networks of polymers that form when monomers are polymerized into well-defined, two-dimensional structures. COFs can be created in a variety of topologies, dictated by the shape of the monomers that comprise it, and typically feature pores that can be customized to perform a range of functions. These materials hold promise for applications including water purification membranes, energy and gas storage, organic electronics, and chemical sensing.

Dichtel explained that COF development is a trial and error process that often fails, as the mechanisms of their formation are not well understood. “We have very limited ability to improve these materials rationally—we need to be able to control their form so we can integrate them into a wide variety of contexts,” he said.

Two-dimensional polymer networks can be utilized for water purification, energy storage, and many other applications, but chemists have long struggled to understand their formation and control their structure.

A breakthrough in COF synthesis came when chemist Brian Smith, a former postdoc in Dichtel’s lab, discovered that certain solvents allowed COFs to disperse as nanoparticles in solution rather than precipitating as powder. These particles became the basis for a new method of growing large, controlled crystalline COFs using nanoparticles as structural “seeds,” then slowly adding monomers to maximize growth while limiting nucleation. “This level of control parallels living polymerization, with well-defined initiation and growth phases,” Dichtel said.

More recently, Dichtel’s group has made significant advances in COF fabrication, successfully casting them into thin films that could be used in membrane and filtration applications.

Further Readings

Hermans

Zhang Z, Jimenez-Izal E, Hermans I, Alexandrova AN.

Dynamic Phase Diagram of Catalytic Surface of Hexagonal Boron Nitride under Conditions of Oxidative Dehydrogenation of Propane.

J Phys Chem Lett. 2019 Jan 3;10(1):20-25.

Love AM, Thomas B, Specht SE, et al.

Probing the Transformation of Boron Nitride Catalysts under Oxidative Dehydrogenation Conditions.

J Am Chem Soc. 2019 Jan 9;141(1):182-190.

Dichtel

Côté AP, Benin AI, Ockwig NW, et al.

Porous, crystalline, covalent organic frameworks.

Science. 2005 Nov 18;310(5751):1166-70.

Bisbey RP, Dichtel WR.

Covalent Organic Frameworks as a Platform for Multidimensional Polymerization.

ACS Cent Sci. 2017 Jun 28;3(6):533-543.

Mulzer CR, Shen L, Bisbey RP, et al.

Superior Charge Storage and Power Density of a Conducting Polymer-Modified Covalent Organic Framework.

ACS Cent Sci. 2016 Sep 28;2(9):667-673.

Smith BJ, Parent LR, Overholts AC, et al.

Colloidal Covalent Organic Frameworks.

ACS Cent Sci. 2017 Jan 25;3(1):58-65.

Li H. Evans AM, Castano I, et al.

Nucleation-Elongation Dynamics of Two-Dimensional Covalent Organic Frameworks.

ChemRxiv, 2019.

Advances in Neuroscience

Speakers

Michal Rivlin
Weizmann Institute of Science

Nieng Yan
Princeton University

Highlights

  • The 80 subtypes of retinal ganglion cells each encode different aspects of vision, such as direction and motion.
  • The “preferences” of these cells were believed to be hard-wired, yet experiments show that retinal ganglion cells can be reprogrammed by exposure to repetitive stimuli.
  • Sodium ion channels control electrical signaling in cells of the heart, muscles, and brain, and have long been drug targets due to their connection to pain signaling.
  • Cryo-electron microscopy has allowed researchers to visualize Nav 7, a sodium ion channel implicated in pain syndromes, and to identify molecules that interfere with its function.

Retinal Computations: Recalculating

The presentation from Michal Rivlin, the Life Sciences Laureate of the 2019 Blavatnik Awards in Israel, began with an optical illusion, a dizzying exercise during which a repetitive, unidirectional pattern of motion appeared to rapidly reverse direction. “You probably still perceive motion, but the image is actually stable now,” Rivlin said, completing a powerful demonstration of the action of direction-sensitive retinal ganglion cells (RGCs), whose mechanisms she has studied for more than a decade. The approximately 80 subtypes of RGCs each encode a different aspect, or modality of vision—motion, color, and edges, as well as perception of visual phenomena such as direction. These modalities are hard-wired into the cells and were thought to be immutable—a retinal ganglion cell that perceived left-to-right motion was thought incapable of responding to visual signals that move right-to-left. Rivlin’s research has challenged not only this notion, but also many other beliefs about the function and capabilities of the retina.

Rather than simply capturing discrete aspects of visual information like a camera and relaying that information to the visual thalamus for processing, the cells of the retina actually perform complex processing functions and display a surprising level of plasticity. Rivlin’s lab is probing both the anatomy and functionality of various types of retinal ganglion cells, including those that demonstrate selectivity, such as a preference for movement in one direction or attunement to increases or decreases in illumination. By exposing these cells to various repetitive stimuli, Rivlin has shown that the selectivity of RGCs can be reversed, even in adult retinas.

Direction-selective retinal ganglion cells that prefer left-to-right motion (Before) can change their directional preference (After) following a repetitive visual stimulus.

These dynamic changes in cells whose preferences were believed to be singular and hard-wired have implications not just for understanding retinal function but for understanding the physiological basis of visual perception. Stimulus-dependent changes in the coding of retinal ganglion cells also have downstream impacts on the visual thalamus, where retinal signals are processed. This unexpected plasticity in retinal cells has led Rivlin and her collaborators to investigate the possibility that the visual thalamus and other parts of the visual system might also display greater plasticity than previously believed.

Targeting Sodium Channels for Pain Treatment

Nature’s deadliest predators may seem an unlikely inspiration for developing new analgesic drugs, but as Nieng Yan, 2019 Blavatnik National Awards Finalist, explained, the potent toxins of some snails, spiders, and fish are the basis for research that could lead to safer alternatives to opioid medications.

Voltage-gated ion channels are responsible for electrical signaling in cells of the brain, heart, and skeletal muscles. Sodium channels are one of many ion channel subtypes, and their connection to pain signaling is well documented. Sodium channel blockers have been used as analgesics for a century, but they can be dangerously indiscriminate, inhibiting both the intended channel as well as others in cardiac or muscle tissues. The development of highly selective small molecules capable of blocking only channels tied to pain signaling seemed nearly impossible until two breakthroughs—one genetic, the other technological—brought a potential path for success into focus.

A 2006 study of families with a rare genetic mutation that renders them fully insensitive to pain turned researchers’ focus to the role of the gene SCN9A, which codes for the voltage-gated sodium ion channel Nav 1.7, in pain syndromes. Earlier studies showed that overexpression of SCN9A caused patients to suffer extreme pain sensitivity, and it was now clear that loss of function mutations resulted in the opposite condition.

A powerful natural toxin derived from corn snails blocks the pore of a voltage-gated sodium channel, halting the flow of ions and inhibiting the initiation of an action potential.

As Yan explained, understanding this channel required the ability to resolve its structure, but imaging techniques available at that time were poorly suited to large, membrane-bound proteins. With the advent of cryo-electron microscopy­­­, Yan and other researchers have not only resolved the structure of Nav 1.7, but also characterized small molecules—mostly derived from animal toxins—that precisely and selectively interfere with its function. Developing synthetic drugs based on these molecules is the next phase of discovery, and it’s one that may happen more quickly than expected. “When I started my lab, I thought resolving this protein’s structure would be a lifetime project, but we shortened it to just five years,” said Yan.

Further Readings

Rivlin

Warwick RA, Kaushansky N, Sarid N, et al.

Inhomogeneous Encoding of the Visual Field in the Mouse Retina.

Curr Biol. 2018 Mar 5;28(5):655-665.e3

Rivlin-Etzion M, Grimes WN, Rieke F.

Flexible Neural Hardware Supports Dynamic Computations in Retina.

Trends Neurosci. 2018 Apr;41(4):224-237.

Vlasits AL, Bos R, Morrie RD, et al.

Visual stimulation switches the polarity of excitatory input to starburst amacrine cells.

Neuron. 2014 Sep 3;83(5):1172-84.

Rivlin-Etzion M, Wei W, Feller MB.

Visual stimulation reverses the directional preference of direction-selective retinal ganglion cells.

Neuron. 2012 Nov 8;76(3):518-25.

Yan

Shen H, Liu D, Wu K, et al.

Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins.

Science. 2019 Mar 22;363(6433):1303-1308.

Pan X, Li Z, Huang X, et al.

Molecular basis for pore blockade of human Na+ channel Nav1.2 by the μ-conotoxin KIIIA.

Science. 2019 Mar 22;363(6433):1309-1313.

Pan X, Li Z, Zhou Q, et al.

Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1.

Science. 2018 Oct 19;362(6412).

Shen H, Li Z, Jiang Y, et al.

Structural basis for the modulation of voltage-gated sodium channels by animal toxins.

Science. 2018 Oct 19;362(6412).

Computer Science

Speakers

Jure Leskovec
Stanford University

Elza Erkip
New York University


Highlights

  • A novel approach to developing machine learning algorithms has improved applications for non-linear datasets.
  • Neural networks can now be used for complex predictive tasks, including forecasting polypharmacy side effects.
  • 5G wireless networks will expand the capabilities of internet-connected devices, providing dramatically faster data transmission and increased reliability.
  • Tools used to design wireless networks can also be used to understand vulnerabilities in the design of online platforms and social networks, particularly as it pertains to user privacy and data anonymization.

Machine Learning with Networks

“For the first time in history, we are using computers to process data at scale to gain novel insights,” said Jure Leskovec, a Blavatnik National Awards Finalist in 2017, 2018, and 2019, describing one aspect of the digital transformation of science, technology, and society. This shift, from using computers to run calculations or simulations to using them to generate insights, is driven in part by the massive data streams available from the Internet and internet-connected devices. Machine learning has catalyzed this transformation, allowing researchers to not only glean useful information from large datasets, but to make increasingly reliable predictions based on it. Just as new imaging techniques reveal previously unknown structures and phenomena in biology, astronomy, and other fields, so too are big data and machine learning bringing previously unobservable models, signals, and patterns to the surface.

This “new paradigm for discovery” has limitations, as Leskovec explained. Machine learning has advanced most rapidly in areas where data can be represented as simple sequences or grids, such as computer vision, image analysis, and speech processing. Analysis of more complex datasets—represented by networks rather than linear sequences—was beyond the scope of neural networks until recently, when Leskovec and his collaborators approached the challenge from a different angle.

The team considered networks as computation graphs, recognizing that the key to making predictions was understanding how information propagates across the network. By training each node in the network to collect information about neighboring nodes and aggregating the resulting data, they can use node-level information to make predictions within the context of the entire network.

Each node within a network collects information from neighboring nodes. Together, this information can be used to make predictions within the context of the network as a whole.

Leskovec shared two case studies demonstrating the broad applicability of this approach. In healthcare, a neural network designed by Leskovec is identifying previously undocumented side effects from drug-drug interactions. Each network node represents a drug or a protein target of a drug, with links between the nodes emerging based on shared side effects, protein targets, and protein-protein interactions. This type of polydrug side effects analysis is infeasible through clinical trials, and Leskovec is working to optimize it as a point-of-care tool for clinicians.

A similar system has been deployed on the online platform Pinterest, where Leskovec serves as Chief Scientist. It has improved the site’s ability to classify users’ preferences and suggest additional content. “We’re generalizing deep learning methodologies to complex data types, and this is leading to new frontiers,” Leskovec said.

Understanding and Engineering Communications Networks

Elza Erkip has never seen a slide rule. In two decades as a faculty researcher and electrical and computer engineer, Erkip, 2010 Blavatnik Awards Finalist, has corrected her share of misconceptions about her field, and about the role of engineering among the scientific disciplines. She joked about stereotypes portraying engineers—most of them men—wielding slide rules or wearing hard hats, but emphasized the importance of raising awareness about the real-life work of engineers. “Scientists want to understand the universe, but engineers use existing scientific knowledge to design and build things,” she explained. “We contribute to discovery, but mostly we want to solve problems, to find solutions that work in the real world.”

Erkip focuses on one of the most impactful areas of 21st century living—wireless communication—and the ever-evolving suite of technologies that support it. She reviewed the rapid progression of wireless device capabilities, from phones that featured only voice calling and text messaging, through the addition of Wi-Fi capability and web browsing, all the way to the smartphones of today, which boast more computing power than the Apollo 11 spacecraft that landed on the moon. She described the next revolution in wireless—5G networks and devices—which promises higher data rates and significant increases in speed and reliability. Tapping the millimeter-wave bands of the electromagnetic spectrum, 5G will rely on different wireless architectures featuring massive arrays of small antennae, which are better suited to propagating shorter wavelengths. The increased bandwidth will enable many more devices to come online. “It won’t just be humans communicating—we’ll have devices communicating with each other,” Erkip said, describing the future connectivity between robots, autonomous cars, home appliances, and sensors embedded in transportation, manufacturing, and industrial equipment.

Despite efforts to anonymize data, many social media sites and online databases remain vulnerable to efforts to match users’ identities across platforms.

Erkip also discussed the application of tools used to understand and build wireless networks to gain insight into privacy issues within social networks. De-anonymization of user data has long plagued online platforms. Studies have shown that it’s often possible to identify and match users across multiple social platforms or databases using publicly available information—a breach that has greater implications for a database of health or voting records than it does for a consumer-oriented site such as Netflix. Erkip is working to understand the fundamental properties of these networks to elucidate the factors that predispose them to de-anonymization attacks.

Further Readings

Leskovec

Zitnik M, Agrawal M, Leskovec J.

Modeling polypharmacy side effects with graph convolutional networks.

Bioinformatics. 2018 Jul 1;34(13):i457-i466.

Erkip

Shirani F, Garg S, Erkip E.

A Concentration of Measure Approach to Database De-anonymization.

IEEE International Symposium on Information Theory. 2019.

Shirani F, Garg S, Erkip E.

Optimal Active social Network De-anonymization Using Information Thresholds.

IEEE International Symposium on Information Theory. 2018.

Materials Science

Speakers

Chiara Daraio
Caltech

Liangbing Hu
University of Maryland, College Park

Highlights

  • Computer-aided manufacturing is enabling researchers to design materials with precisely tuned properties, such as responsiveness to light, temperature, or moisture.
  • Structured materials can mimic robots or machines, changing shape and form repeatedly in the presence of various stimuli.
  • Ultra-strong, lightweight wood-based materials made of nanocellulose fibers may one day resolve some of the world’s most pressing challenges in water, energy and sustainability, replacing transparent plastic packaging, window glass, and even steel and other alloys in vehicles and buildings.

Mechanics of Robotic Matter

Chiara Daraio’s work challenges the traditional definition of words like material, structure, and robot.  Working at the intersection of physics, materials science, and computer science, she designs materials with novel properties and functionalities, enabled by computer-aided design and 3D fabrication. Rather than considering a material as the foundation for assembling a structure, Daraio, 2019 Blavatnik National Awards Finalist, designs materials with intricate structures in unique and complex geometries.

Daraio demonstrated a series of responsive materials—those that morph in the presence of stimuli such as temperature, light, moisture, or salinity. In their simplest forms, these materials change shape—a piece of heat-responsive material folds and unfolds as air temperature changes, or a leaf-shaped hydro-sensitive material opens and closes as it transitions from wet to dry. In more complex forms, materials can display time-dependent responses, as shown in a video demonstration of a row of polymer strips changing shape at different rates, depending on their thickness. Daraio showed how computer-graphical approaches allow researchers to design a single material with different properties in different regions, allowing complex actuation in a time-dependent manner, such as a polymer “flower” with interconnecting leaves taking shape and a polymer “ribbon” slowly interweaving a knot.

A thin foil elastomer comprised of materials with alternating temperature-sensitivity (heat and cold) folds up and “walks” across a table as the temperature varies.

Conventional ideas dictate that a robot is a programmable machine capable of completing a task. “But what if the material is the machine?” asked Daraio, showing the remarkable capabilities of a thin liquid crystal elastomer foil composed of one heat-sensitive and one cold-sensitive material. At room temperature, the foil is flat. Heat from a warm table causes it to curl upward, turn over, and “walk” forward. “As long as there’s some kind of external environmental stimulus, we can design a material that can repeatedly perform actions in time,” Daraio said. Similar responsive materials have been used in a self-deploying solar panel that [remove folds and] unfolds in response to heat.

Materials have been “the seeds of technological innovation” throughout human history, and Daraio believes that structured materials will enable new functionalities at the macroscale—for use in wearables such as helmets as well as in smart building technologies—and at the microscale, where responsive materials could be used for medical diagnostics or drug delivery.

Sustainable Applications for Wood Nanotechnologies

Wood, glass, plastic, and steel are among the most ubiquitous materials on Earth, and Liangbing Hu, 2019 Blavatnik National Awards Finalist, is rethinking them all. Inspired by the global need to develop sustainable materials, Hu turned to the most plentiful source of biomass on Earth— trees—to create a new generation of wood-based materials with astonishing properties. Hu relies on nanocellulose fibers, which can be engineered to serve as alternatives to commonly used unsustainable or energy-intensive materials.

Hu introduced a transparent film that could pass for plastic and can be used for packaging, yet is ten times stronger and far more versatile. This transparent nanopaper, made of nanocellulose fibers, could also be used as a display material in flexible electronics or as a photonic overlay that boosts the efficiency of solar cells by 30%.

Hu has also tested transparent wood—a heavier-gauge version of nanopaper made by removing lignin from wood and injecting the channels with a clear polymer—as an energy-saving building material. More than half of home energy loss is due to poor wall insulation and leakage through window glass. By Hu’s calculations, replacing glass windows with transparent wood would also provide a six-fold increase in thermal insulation. Pressed, delignified wood has also proven to be a superior material for wall insulation. Used on roofs, it is a highly efficient means of passive cooling—the material absorbs heat and then re-radiates it, cooling the surface below it by about ten degrees.

White delignified wood is pressed to increase its strength. It can be used on roofs to passively cool homes by absorbing and re-radiating light, cooling the area below it by about ten degrees.

Comparisons of mechanical strength between wood and steel are almost laughable, unless the wood is another of Hu’s creations—the aptly named “superwood.” Delignified and compressed to align the nanocellulose fibers, even inexpensive woods become thinner and 10-20 times stronger. Superwood rivals steel in strength and durability, and could become a viable alternative to steel and other alloys in buildings, vehicles, trains, and airplanes. Sustainable sourcing would eliminate pollution and carbon dioxide associated with steel production, and its lightweight profile could drastically improve vehicle fuel efficiency.

Further Readings

Daraio

Celli P, McMahan C, Ramirez B, et al.

Shape-morphing architected sheets with non-periodic cut patterns.

Soft Matter. 2018 Dec 12;14(48):9744-9749.

Chen T, Bilal OR, Shea K, Daraio C.

Harnessing bistability for directional propulsion of soft, untethered robots.

Proc Natl Acad Sci USA. 2018 May 29;115(22):5698-5702.

Bauhofer AA, Krödel S, Rys J, et al.

Harnessing Photochemical Shrinkage in Direct Laser Writing for Shape Morphing of Polymer Sheets.

Adv Mater. 2017 Nov;29(42).

Hu

Song J, Chen C, Zhu S, et al.

Processing bulk natural wood into a high-performance structural material.

Nature. 2018 Feb 7;554(7691):224-228.

Huang J, Zhu H, Chen Y, et al.

Highly transparent and flexible nanopaper transistors.

ACS Nano. 2013 Mar 26;7(3):2106-13.

Huang J, Zhu H, Chen Y, et al.

Novel nanostructured paper with ultrahigh transparency and ultrahigh haze for solar cells.

Nano Lett. 2014 Feb 12;14(2):765-73.

Zhu M, Song J, Li T, et al.

Highly Anisotropic, Highly Transparent Wood Composites.

Adv Mater. 2016 Jul;28(26):5181-7.

Li T, Zhai Y, He S, et al.

A radiative cooling structural material.

Science. 2019 May 24;364(6442):760-763.

Zhu H, Luo W, Ciesielski PN, et al.

Wood-Derived Materials for Green Electronics, Biological Devices, and Energy Applications.

Chem Rev. 2016 Aug 24;116(16):9305-74.

Medicine and Medical Diagnostics

Speakers

Nicholas Navin
MD Anderson Cancer Center

Wei Min
Columbia University

Highlights

  • Tumor cells are genetically heterogeneous, complicating efforts to sequence DNA from tumor tissue samples.
  • Techniques for isolating and sequencing single-cell samples have transformed the study of cancer genetics.
  • Stimulated Ramen scattering, a non-invasive imaging technique, can visualize processes including glucose uptake and fatty acid metabolism within living cells.

Single Cell Genomics: A Revolution in Cancer Biology

Nicholas Navin, 2019 Blavatnik National Awards Finalist, doesn’t use the word “revolution” lightly, but when it comes to the field of single-cell genomics and its impact on cancer research, he stands by the term. Over the past ten years, DNA sequencing of single tumor cells has led to major discoveries about the progression of cancer and the process by which cancer cells resist treatment.

Unlike healthy tissue cells, tumor cells are characterized by genomic heterogeneity. Samples from different areas of the same tumor often contain different mutations or numbers of chromosomes. This diversity has long piqued researchers’ curiosity. “Is it stochastic noise generated as tumor cells acquire different mutations, or could this diversity be important for resistance to therapy, invasion, or metastasis?” Navin asked.

Answering that question required the ability to do comparative studies of single tumor cells, a task that was long out of reach. DNA sequencing technologies historically required a large sample of genetic material—a tricky proposition when sampling a highly diverse population of tumor cells. Some mutations, which could drive invasion or resistance, may be present in just a few cells and thus not be represented in the results. Navin was part of the first team to develop a method for excising a single cancer cell from a tumor, amplifying the DNA, and producing an individualized genetic sequence. As amplification and sequencing methods have improved, so too have the insights gleaned from single-cell genomic studies, which Navin likens to “paleontology in tumors”—the notion that a sample taken at a single point in time can allow researchers to make inferences about tumor evolution.

Single-cell genomic studies reveal that some cancer cells have innate mechanisms of resistance to chemotherapy, and undergo further transcriptional changes that enhance this resistance.

Single-cell studies have contradicted the idea of a stepwise evolution of cancer cells, with one mutation leading to another and ultimately tipping the scales toward malignancy. Instead, Navin’s studies reveal a punctuated evolution, whereby many cells simultaneously become genetically unstable. Longitudinal studies of single-cell samples in patients with triple-negative breast cancer are beginning to answer questions about how cancer cells evade treatment, showing that cells that survive chemotherapy have innate resistance, and then undergo further transcriptional changes during treatment, which increase resistance.

Translating these findings to the clinic is a longer-term process, but Navin envisions single-cell genomics will significantly impact strategies for targeted therapy, non-invasive monitoring, and early cancer detection.

Chemical Imaging in Biomedicine

Wei Min, a Blavatnik Awards Finalist in 2012 and 2019, concluded the session with a visually striking glimpse into the world of stimulated Raman scattering (SRS) microscopy. This noninvasive imaging technique provides both sub-cellular resolution and chemical information about living cells, while transcending some of the limitations of fluorescence-based optical microscopy. The probes used to tag molecules for fluorescent imaging can alter or destroy small molecules of interest, including glucose, lipids, amino acids, or neurotransmitters. Rather than using tags, SRS builds on traditional Raman spectroscopy, which captures and analyzes light scattered by the unique vibrational frequencies between atoms in biomolecules. The original method, first pioneered in the 1930s, is slow and lacks sensitivity, but in 2008, Min and others improved the technique.

SRS has since become a leading method for label-free visualization of living cells, providing an unprecedented window into cellular activities. Using SRS and a variety of custom chemical tags—“vibrational tags,” as Min described them—bound to biomolecules such as DNA or RNA bases, amino acids, or even glucose, researchers can observe the dynamics of biological functions. SRS has visualized glucose uptake in neurons and malignant tumors, and has been used to observe fatty acid metabolism, a critical step in understanding lipid disorders. Imaging small drug molecules is notoriously difficult, but Min reported the results of experiments using SRS to tag therapeutic drug molecules and study their activity within tissues.

Stimulated Raman scattering microscopy uses chemical tags to image small biological molecules in living cells. The technique can visualize cellular processes including glucose uptake in healthy cells and tumor cells.

A recent breakthrough in SRS technology involves pairing it with Raman dyes to break the “color barrier” in optical imaging. Due to the width of the fluorescent spectrum, labels are limited to five or six colors per sample, which prevents researchers from imaging many structures within a tissue sample simultaneously. Min has introduced a hybrid imaging technique that allows for super-multiplexed imaging—up to 10 colors in a single cell image—and utilizes a dramatically expanded palette of Raman frequencies that yield at least 20 distinct colors.

Further Readings

Navin

Kim C, Gao R, Sei E, et al.

Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single-Cell Sequencing.

Cell. 2018 May 3;173(4):879-893.e13.

Casasent AK, Schalck A, Gao R, et al.

Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing.

Cell. 2018 Jan 11;172(1-2):205-217.e12.

Gao R, Davis A, McDonald TO, et al.

Punctuated copy number evolution and clonal stasis in triple-negative breast cancer.

Nat Genet. 2016 Oct;48(10):1119-30.

Wang Y, Navin NE.

Advances and applications of single-cell sequencing technologies.

Mol Cell. 2015 May 21;58(4):598-609.

Navin NE.

Cancer genomics: one cell at a time.

Genome Biol. 2014 Aug 30;15(8):452.

Wang Y, Waters J, Leung ML, et al.

Clonal evolution in breast cancer revealed by single nucleus genome sequencing.

Nature. 2014 Aug 14;512(7513):155-60.

Min

Xiong H, Shi L, Wei L, et al.

Stimulated Raman excited fluorescence spectroscopy and imaging.

Nat Photonics. 2019; (3) 412–417.

Xiong H, Qian N, Miao Y, et al.

Stimulated Raman Excited Fluorescence Spectroscopy of Visible Dyes.

J Phys Chem Lett. 2019 Jul 5;10(13):3563-3570.

Zhang L, Shi L, Shen Y, et al.

Spectral tracing of deuterium for imaging glucose metabolism.

Nat Biomed Eng. 2019 May;3(5):402-413.

Shen Y, Hu F, Min W.

Raman Imaging of Small Biomolecules.

Annu Rev Biophys. 2019 May 6;48:347-369.

Wei M, Shi L, Shen Y, et al.

Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy.

Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6608-6617.

Shi L, Zheng C, Shen Y, et al.

Optical imaging of metabolic dynamics in animals.

Nat Commun. 2018 Aug 6;9(1):2995.

Recognizing Breakthrough Scientists in the Tri-State

The shield for the Blavatnik Awards for Young Scientists.

New breakthroughs in controlling mosquito populations, quantum gravity and reducing chemical byproduct waste are among the cutting edge research being honored by the 2019 Blavatnik Regional Awards for Young Scientists.

Published September 14, 2019

By Kamala Murthy

This year the Blavatnik Regional Awards for Young Scientists received 137 nominations from 20 academic institutions in the tri-state area. A jury of distinguished senior scientists and engineers from leading academic institutions selected three outstanding scientists as Winners who will each receive a $30,000 unrestricted prize, and six Finalists (two from each category) who each will collect a $10,000 unrestricted prize.

Supporting outstanding scientists from academic research institutions across New York, New Jersey, and Connecticut since 2007, the Blavatnik Regional Awards for Young Scientists recognize and honor postdoctoral researchers in three scientific disciplinary categories: Life Sciences, Physical Sciences & Engineering, and Chemistry.

The 2019 Blavatnik Regional Awards Winners are:

Life Sciences: Laura Duvall, PhD, nominated by The Rockefeller University (now at Columbia University). Dr. Duvall’s discovery of two key molecules in mosquitos that inhibit blood-feeding and breeding has worldwide implications for controlling mosquito populations and the spread of diseases such as Dengue and Zika. At the time of nomination, Dr. Duvall was a trainee of the 2007 Blavatnik Regional Awards Faculty Winner, Leslie Vosshall of The Rockefeller University.

Physical Sciences & Engineering: Netta Engelhardt, PhD, nominated by Princeton University (now at Massachusetts Institute of Technology). Dr. Engelhardt’s research at the interface of general relativity and quantum field theory is answering complex questions about the fundamentals of our universe, including the remarkable explanation for the origin of black hole entropy. Her work is integral to the understanding of how the fabric of the universe at large-scale is encoded in quantum gravity.

Chemistry: Juntao Ye, PhD, nominated by Cornell University (now at Shanghai Jiao Tong University in China). Improving synthetic efficiency while lowering the cost of synthesis is a primary goal for pharmaceutical industries. Ye invented several new methods that allow for converting readily available chemicals into value-added and pharmaceutically relevant products in a highly efficient and economical manner, while reducing chemical byproduct waste. These methods could accelerate the pace of drug discovery through improving efficiency in synthesizing complex and bioactive compounds.

The cutting-edge discoveries being recognized this year cover an incredibly disparate breadth of work in quantum gravity, drug discovery, control of mosquito populations and underwater photographic imagery. These are the advances that will change our world.

Ellis Rubinstein

2019 Blavatnik Regional Awards Finalists

Life Sciences

Carla Nasca, PhD, nominated by The Rockefeller University — recognized for the discovery of acetyl-L-carnitine (LAC) as a novel modulator of brain rewiring and a possible new treatment for depression that acts by turning on and off specific genes related to the neurotransmitter glutamate.

Liling Wan, PhD, nominated by The Rockefeller University (currently transitioning to the University of Pennsylvania) — recognized for identifying a previously unknown function of a protein called ENL, which has the ability to read epigenetic information on our chromosomes and activate genes that perpetuate tumor growth. Elucidating the structure and mechanism of ENL has guided ongoing development of drugs to treat cancers.

Physical Sciences & Engineering

Derya Akkaynak, PhD, nominated by Princeton University — recognized for significant breakthroughs in computer vision and underwater imaging technologies, resolving a fundamental technological problem in the computer vision community — the reconstruction of lost colors and contrast in underwater photographic imagery — which will have real implications for oceanographic research.

Matthew Yankowitz, PhD, nominated by Columbia University (now at the University of Washington) — recognized for groundbreaking experimental work modifying the electronic properties of a new class of two-dimensional materials, known as van der Waal materials. van der Waal materials have generated tremendous interest due to their properties and the promise they show for use in next-generation optoelectronic and electronic devices, future computing, and telecommunications technologies. Dr. Yankowitz’s work led to the discovery that applied pressure can be used to induce superconductive properties in multi-layer graphene, and has significantly advanced a new area of research recently coined “twistronics.”

Chemistry

Yaping Zang, PhD, nominated by Columbia University — recognized for innovatively using electrochemistry and electrical fields in conjunction with scanning tunneling microscopy techniques to drive chemical reactions. This work provides a deeper understanding of the reaction mechanisms and opens new avenues for the use of electricity as a catalyst in chemical reactions.

Igor Dikiy, PhD, nominated by the Advanced Science Research Center at The Graduate Center, CUNY — recognized for completing the first study of G-protein–coupled receptor (GPCR) fast sidechain dynamics using NMR (nuclear magnetic resonance) spectroscopy to shed light on the molecular mechanisms of cell signaling. GPCRs control a variety of processes in the human body and are targets for over 30% of all FDA-approved drugs. Elucidating the mechanisms of GPCR signaling will enable researchers to design more effective drugs.

Honoring the Blavatnik Regional Award Winners and Finalists

The 2019 Blavatnik Regional Awards Winners and Finalists will be honored at the New York Academy of Sciences’ Annual Gala at Cipriani 25 Broadway in New York on Monday, November 11, 2019.

To learn more about this year’s Blavatnik Awards honorees, please visit the Blavatnik Awards website and follow us on Facebook and Twitter: @BlavatnikAwards

The New Transformers: Innovators in Regenerative Medicine

Overview

The human body regenerates itself constantly, replacing old, worn-out cells with a continuous supply of new ones in almost all tissues. The secret to this perpetual renewal is a small but persistent supply of stem cells, which multiply to replace themselves and also generate progeny that can differentiate into more specialized cell types. For decades, scientists have tried to isolate and modify stem cells to treat disease, but in recent years the field has accelerated dramatically.

A major breakthrough came in the early 21st century, when researchers in Japan figured out how to reverse the differentiation process, allowing them to derive induced pluripotent stem (iPS) cells from fully differentiated cells. Since then, iPS cells have become a cornerstone of regenerative medicine. Researchers can isolate cells from a patient, produce iPS cells, genetically modify them to repair any defects, then induce the cells to form the tissue the patient needs regenerated.

On April 26, 2019, the New York Academy of Sciences and Takeda Pharmaceuticals hosted the Frontiers in Regenerative Medicine Symposium to celebrate 2019 Innovators in Science Award winners and highlight the work of researchers pioneering techniques in regenerative medicine. Presentations and an interactive panel session covered exciting basic research findings and impressive clinical successes, revealing the immense potential of this rapidly developing field.

Symposium Highlights

  • New cell lines should reduce the time and cost of developing stem cell-derived therapies.
  • The body’s microbiome primes stem cells to respond to infections.
  • iPS cell-derived therapies have already treated a deadly genetic skin disease and age-related macular degeneration.
  • Polyvinyl alcohol is a superior substitute for albumin in stem cell culture media.
  • A newly isolated type of stem cell reveals the stepwise process driving early embryo organization.

Speakers

Shinya Yamanaka
Kyoto University

Shruti Naik
New York University

Michele De Luca
University of Modena and Reggio Emilia

Masayo Takahashi
RIKEN Center for Biosystems Dynamics Research

Hiromitsu Nakauchi
Stanford University and University of Tokyo

Brigid L.M. Hogan
Duke University School of Medicine

Emmanuelle Passegué
Columbia University Irving Medical Center

Hans Schöler
Max Planck Institute for Molecular Biomedicine

Austin Smith
University of Cambridge

Moderator: Azim Surani
University of Cambridge

Sponsors

Recent Progress in iPS Cell Research Application

Speakers

Shinya Yamanaka
Kyoto University

Highlights

  • Current protocols for using induced pluripotent stem (iPS) cells clinically are slow and expensive.
  • HLA “superdonor” iPS cell lines can be used to treat multiple patients, reducing costs.
  • A unique academic-industry partnership is helping iPS cell therapies reach the clinic.

Faster, Cheaper, Better

Shinya Yamanaka of Kyoto University, gave the meeting’s keynote presentation, summarizing his laboratory’s recent work using induced pluripotent stem (iPS) cells for regenerative medicine. The first clinical trial using iPS cells to treat age-related macular degeneration started five years ago. In his clinical trial, physicians isolated somatic cells from a patient, then used developed culture techniques to derive iPS cells from them. iPS cells can proliferate and differentiate into any type of cell in the body, which can then be transplanted back into the patient. Experiments over the past five years have shown that this approach has the potential to treat diseases ranging from age-related macular degeneration to Parkinson’s disease.

However, this autologous transplantation strategy is slow and expensive. “It takes up to a year just evaluating one patient, [and] it costs us almost one million US dollars,” said Yamanaka. Before transplanting the differentiated cells, the researchers evaluated the entire iPS cell derivation and iPS cell differentiation processes, adding to time and cost. As another strategy, Yamanaka’s team is working on the iPS Cell Stock for Regenerative Medicine. Here, iPS cells are derived from blood cells of healthy donors, not the patients, and are stocked. The primary problem with this approach is the human leukocyte antigen (HLA) system, which encodes multiple cell surface proteins. Each person has a specific combination of HLA genes, or haplotype, defining the HLA proteins expressed on their own cells. The immune system recognizes and eliminates any cell expressing non-self HLA proteins. Because there are millions of potential HLA haplotypes, cells derived from one person will likely be rejected by another.

The homozygous “superdonor” cell line has limited immunological diversity, allowing it to match multiple patients.

The homozygous “superdonor” cell line has limited immunological diversity, allowing it to match multiple patients.

To address that, Yamanaka and his colleagues are collaborating with the Japanese Red Cross to develop “superdonor” iPS cells. These cells carry homozygous alleles for different human lymphocyte antigen (HLA) genes, limiting their immunological diversity and making them match multiple patients. So far, the team has created four “superdonor” cell lines, allowing them to generate cells compatible with 40% of the Japanese population. Those cells are now being used in clinical trials treating macular degeneration and Parkinson’s disease, with more indications planned.

“So far so good,” said Yamanaka, but he added that “in order to cover 90% of the Japanese population we would need 150 iPS cell lines, and in order to cover the entire world we would need over 1,000 lines.” It took the group about five years to generate the first four lines, so simply repeating the process that many more times isn’t practical.

Instead, Yamanaka hopes to take the HLA reduction a step further, knocking out most of the major HLA genes to generate cells that will survive in large swaths of the population. However, simply knocking out entire families of genes isn’t enough. Natural killer cells attack cells that are missing particular cell surface antigens, so the researchers had to leave specific markers in the cells, or reintroduce them transgenically. Natural killer and T cells from various donors ignore leukocytes derived from these highly engineered iPS cells, proving that the concept works. With this approach, just ten lines of iPS cells should yield a range of donor cells suitable for any human HLA combination. Yamanaka expects these gene-edited iPS cells to be available in 2020.

By 2025, Yamanaka hopes to announce “my iPS cell” technology. This technology will reduce the cost and time for autologous transplantation to about $10,000 and one month per patient.

While preclinical and early clinical trials on iPS cells have yielded promising results, the new therapies must still cross the “valley of death,” the pharmaceutical industry’s term for the unsuccessful transition and industrialization of innovative ideas identified in academia to routine clinical use. In an effort to make that process more reliable, Yamanaka and his colleagues have begun a unique collaboration with Takeda Pharmaceutical Company Limited, Japan’s largest drug maker. The effort involves 100 scientists, 50 each from the company and academic laboratories. The corporate researchers gain access to the latest basic science developments on iPS cell technology, while the academics can use the company’s cutting-edge R&D know-how equipment and vast chemical libraries.

In one project, the collaborators used iPS cells to derive pancreatic islet cells, and then encapsulated the cells in an implantable device to treat type 1 diabetes. The system successfully decreased blood glucose in a mouse model, and the team is now scaling up cell production to test it in humans in the future. Another effort identified chemicals in Takeda’s compound library that speed cardiomyocyte maturation, which the researchers are now using to improve iPS cell-derived treatments for heart failure. In a third project, the team has modified iPS cell-derived T cells to identify and attack tumors, again showing promising results in a mouse model.

Further Reading

Yamanaka

Fujimoto T, Yamanaka S, Tajiri S, et al.

In Vivo Regeneration of Interspecies Chimeric Kidneys Using a Nephron Progenitor Cell Replacement System.

Scientific Report. 2019; 9:6965.

Karagiannis P, Yamanaka S, Saito MK.

Application of Induced Pluripotent Stem Cells to Primary Immunodeficiency Diseases.

Experimental Hematology. 2019;71:43-50.

The Winners’ Circle

Speakers

Shruti Naik
New York University

Michele De Luca
University of Modena and Reggio Emilia

Highlights

  • Epithelial barriers must distinguish harmless commensal bacteria from dangerous pathogens.
  • Mice lacking commensal bacteria exhibit defective immune responses.
  • Inflammation causes persistent changes in epithelial stem cells, priming them for subsequent immune responses.
  • Modified iPS cells can be used to cure a patient with a deadly genetic skin defect.
  • A small population of self-renewing stem cells maintains human skin cells.

Sparring Partners

Shruti Naik, Early-Career Scientist winner of the 2019 Innovators in Science Award, discussed her work on epithelial barriers. These barriers, which include skin and the linings of the gut, lungs, and urogenital tract, exhibit nuanced responses to the many microbes they encounter. Injuries and pathogenic infections trigger prompt inflammatory responses, but the millions of harmless commensal bacteria that live on these surfaces don’t. How does the epithelium know the difference?

To ask that question, Naik first studied germ-free mice, which lack all types of bacteria. These animals have defective immune responses against pathogens that affect epithelia, so commensal bacteria are clearly required for developing normal epithelial immunity. Naik inoculated the germ-free mice with bacterial strains found either on the skin or in the guts of normal mice, then assessed their immune responses in those two compartments.

“When you gave gut-tropic bacteria, you were essentially able to rescue immunity in the gut but not the skin, and conversely when you gave skin-tropic bacteria, you were able to rescue immunity in the skin and not the gut,” said Naik. Even though the commensal bacteria caused no inflammation, they did activate certain T cells in the epithelia they colonized, apparently preparing those tissues for subsequent attacks by pathogens.

Next, Naik took germ-free mice inoculated with Staphylococcus epidermidis, a normal skin commensal bacterium, and challenged them with an infection by Candida albicans, a pathogenic yeast. The bacterially primed mice produced a much more robust immune response against the yeast infection than control animals that hadn’t gotten S. epidermidis. Naik confirmed that this immune training effect operates through the T cell response she’d seen before. “You essentially develop an immune arsenal to your commensals that helps protect against pathogens,” Naik explained, adding that each epithelial barrier requires its own commensal bacteria to trigger this response.

Augmented wound repair in post-inflammation skin reveals that naive and inflammation-educated skin stem cells respond differently to subsequent stresses.

Augmented wound repair in post-inflammation skin reveals that naive and inflammation-educated skin stem cells respond differently to subsequent stresses.

The response to epithelial commensals is remarkably durable; Naik found that the skin T cells in the inoculated mice remained on alert a year after their initial activation. That led her to wonder whether non-hematopoietic cells, especially epithelial stem cells, contribute to immunological memory in the skin.

To probe that, Naik and a colleague used a mouse model in which the topical drug imiquimod induces a temporary psoriasis-like skin inflammation. By tracing the lineages of cells in the animals’ skin, the researchers found that epithelial stem cells expand during this inflammation, and then persist. Challenging the mice with a wound one month after the inflammation resolves leads to faster healing than if the mice hadn’t had the inflammation. Several other models of wound healing yielded the same result. The investigators concluded that naive and inflammation-educated skin stem cells respond differently to subsequent stresses.

Naik’s team found that inflammation causes persistent changes in skin stem cells’ chromatin organization. Using a clever reporter gene assay, they demonstrated that the initial inflammation leaves inflammatory gene loci more open in the chromatin, making them easier to activate after subsequent insults. “What was really surprising to us was that this change never fully resolved,” said Naik. Even six months after the acute inflammation, skin stem cells retained the distinct post-inflammatory chromatin structure and the ability to heal wounds quickly. This chronic ready-for-action state isn’t always beneficial, though. Naik noticed that the mice that had had the inflammatory treatment were more prone to developing tumors, for example.

In establishing her new laboratory, Naik has now turned her focus to another aspect of epithelial immunity: the link between immune responses and tissue regeneration. She looked first at a type of T cells found in abundance around hair follicles on skin. Mice lacking these cells exhibit severe delays in wound healing, apparently as a result of failing to vascularize the wound area. That implies a previously unknown role for inflammatory T cells in vascularization, which Naik and her lab are now probing.

Skin Deep

Michele De Luca, Senior Scientist winner of the 2019 Innovators in Science Award, has developed techniques for regenerating human skin from transgenic epidermal stem cells. Researchers first isolated holoclones, or cells derived from a single epidermal stem cell, over 30 years ago. These cells can be used to grow sheets of skin in culture for both research and clinical use, but scientists have only recently begun to elucidate how the process works.

The first stem cell-derived therapies tested in humans were for skin and eye burns, allowing doctors to regenerate and replace burned epidermal tissue from a patient’s own stem cells. That’s the basis of Holoclar, a stem cell-based treatment for severe eye burns approved in Europe in 2015.

Holoclar and similar procedures work well for injured patients with normal epithelia. “We wanted to genetically modify those cells in order to address one of the most important genetic diseases in the dermatology field, which is epidermolysis bullosa (EB), a devastating skin disease,” said De Luca. In EB, patients carry a genetic defect in cell adhesion that causes severe blisters all over their skin and prevents normal healing. A large number of EB patients die as children from the resulting infections, and those who survive seldom get beyond young adulthood before succumbing to squamous cell carcinomas.

De Luca developed a strategy to isolate stem cells from a skin biopsy, repair the genetic defect in these cells with a retroviral vector, and then grow new skin in culture that can be transplanted back to the patient, replacing their original skin with genetically repaired skin. In 2015, the researchers carried out the procedure on a young boy named Hassan, who had arrived in the burn unit of a German hospital with EB after fleeing Syria. The burn unit was only able to offer palliative care, and his prognosis was poor because of his constant blistering and infections. De Luca’s team received approval to perform their gene therapy on him.

The new strategy, which combines cell and gene therapy, resulted in the restoration of normal skin adhesion in Hassan.

After isolating and modifying epidermal stem cells from Hassan and growing new sheets of skin in culture, De Luca’s team re-skinned the patient’s arms and legs, then his abdomen and back. The complete procedure took about three months. The new skin resists blister formation even when rubbed and heals normally from minor wounds. In the ensuing three and a half years, Hassan has begun growing normally and living an ordinary, healthy life.

Detailed analysis of skin biopsies showed that Hassan’s epidermis has normal cellular adhesion machinery and revealed that his skin is now derived from a population of proliferating transgenic stem cells, with no single clone dominating. By tracing the lineages of cells carrying the introduced transgene, De Luca was able to identify self-renewing transgenic stem cells, intermediate progenitor cells, and fully differentiated stem cells, indicating normal skin growth and replacement.

Besides being good news for the patient, the results confirmed a longstanding theory of skin regeneration. “These data formally prove that the human epidermis is sustained only by a small population of long-lived stem cells that generates [short-lived epithelial] progenitors,” said De Luca, adding that “with this in mind, we’ve started doing other clinical trials.”

The researchers plan to continue targeting junctional as well as dystrophic forms of EB, both of which are genetically distinct from EB simplex. Initial experiments revealed that in these conditions, transplant recipients developed mosaic skin, where some areas continued to be produced from cells lacking the introduced genetic repair. The non-transgenic cells appeared to be out-competing the transgenic cells and supplanting them, undermining the treatment. De Luca and his colleagues developed a modified strategy that gave the transgenic cells a competitive advantage. This approach and additional advances should allow them to achieve complete transgenic skin coverage.

Further Readings

Naik

Bukhari S, Mertz AF, Naik S.

Eavesdropping on the Conversation between Immune Cells and the Skin Epithelium.

International Immunology. 2019;dyx088.

Kobayashi T, Naik S, Nagao K.

Choreographing Immunity in the Skin Epithelial Barrier.

Immunity.2019;50(3):552-565.

Naik S, Larsen SB, Gomez NC, et al.

Inflammatory Memory Sensitizes Skin Epithelial Stem Cells to Tissue Damage.

Nature. 2017;550:475-480.

.

De Luca

De Rosa L, Seconetti AS, De Santis G, et al.

Laminin 332-Dependent YAP Dysregulation Depletes Epidermal Stem Cells in Junctional Epidermolysis Bullosa.

Cell Reports. 2019; 27(7):2036-2049.e6.

Hirsch T, Rothoeft T, Teig N, et al.

Regeneration of the Entire Human Epidermis Using Transgenic Stem Cells.

Nature. 2019;551(7680):327-332.

Latella MC, Cocchiarella F, De Rosa L, et al.

Correction of Recessive Dystrophic Epidermolysis Bullosa by Transposon-Mediated Integration of COL7A1 in Transplantable Patient-Derived Primary Keratinocytes.

The Journal of Investigative Dermatology. 2017;137(4):836-44.

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Good for What Ails Us

Speakers

Masayo Takahashi
RIKEN Center for Biosystems Dynamics Research

Hiromitsu Nakauchi
Stanford University and University of Tokyo

Highlights

  • The first clinical use of iPS cells in humans replaced retinal cells in a patient with age-related macular degeneration.
  • “Superdonor” stem cells can evade immune rejection in multiple patients.
  • Culturing hematopoietic stem cells has been an ongoing challenge for immunologists.
  • Polyvinyl alcohol, used in making school glue, is a superior substitute for bovine serum albumin in stem cell culture media.
  • Large doses of hematopoietic stem cells may obviate the need for immunosuppression in stem cell therapy.

An iPS Cell for an Eye

Masayo Takahashi, of RIKEN Center for Biosystems Dynamics Research, began her talk with a brief description of the new Kobe Eye Center, a purpose-built facility designed to house a complete clinical development pipeline dedicated to curing eye diseases. “Not only cells, not only treatments, but a whole care system is needed to cure the patients,” said Takahashi. In keeping with that philosophy, the Center includes everything from research laboratories to a working eye hospital and a patient welfare facility.

Takahashi’s recent work has focused on treating age-related macular degeneration (AMD). In AMD, the retinal pigment epithelium that nourishes other retinal cells accumulates damage, leading to progressive vision loss. AMD is the most common cause of serious visual impairment in the elderly in the US and EU, and there is no definitive treatment. Fifteen years ago, Takahashi and her colleagues derived retinal pigment epithelial cells from monkey embryonic stem cells and successfully transplanted them into a rat model of AMD, treating the condition in the rodents. They were hesitant to extend the technique to humans, though, because it required suppressing the recipient’s immune response to prevent them from rejecting the monkey cells.

The advent of induced pluripotent stem (iPS) cell technology pointed Takahashi toward a new strategy, in which she took cells from a patient, derived iPS cells from them, and then prompted those cells to differentiate into retinal pigment epithelial cells that were perfectly compatible with the patient’s immune system. Her team then transplanted a sheet of these cells into the patient. That experiment, in 2014, was the first clinical use of iPS cells in humans. “The grafted cells were very stable,” said Takahashi, who has checked the graft in multiple ways in the ensuing years.

Having proven that iPS cell-derived retinal grafts can work, Takahashi and her colleagues sought to make the procedure cheaper and faster. Creating customized iPS cells from each patient is a huge undertaking, so instead the team investigated superdonor iPS cells that can be used for multiple patients. These cells, described by Shinya Yamanaka in his keynote address, express fewer types of human leukocyte antigens than most patients, making them immunologically compatible with large swaths of the population. Just four lines of superdonor iPS cells can be used to derive grafts for 40% of all Japanese people.

Transplantation of an iPS cell-derived sheet into the retina ultimately proved successful.

Transplantation of an iPS cell-derived sheet into the retina ultimately proved successful.

In the next clinical trial, Takahashi’s lab performed several tests to confirm that the patients’ immune cells would not react with the superdonor cells, before proceeding with the first retinal pigment epithelial graft. Nonetheless, after the graft the researchers saw a minuscule fluid pocket in the patient’s retina, apparently due to an immune reaction. Clinicians immediately gave the patient topical steroids in the eye to suppress the reaction. “Then after three weeks or so, the reaction ceased and the fluid was gone, so we could control the immune reaction to the HLA-matched cells,” said Takahashi. Four subsequent patients showed no reaction whatsoever to the iPS superdonor-derived grafts.

While the retinal grafts were successful, none of the patients have shown much improvement in visual acuity so far. Takahashi explained that subjects in the clinical trial all had very severe AMD and extensive loss of their eyes’ photoreceptors. “I think if we select the right patients, we could get good visual acuity if their photoreceptors still remain,” said Takahashi.

Takahashi finished with a brief overview of her other projects, including using aggregates of iPS cells and embryonic stem cells to form organoids, which can self-organize into a retina. She hopes to use this system to develop new therapies for retinitis pigmentosa, another major cause of vision loss. Finally, Takahashi described a project aimed at reducing the cost and increasing the efficacy of stem cell therapies even further by employing a sophisticated laboratory robot. The system, called Mahoro, is capable of learning techniques from the best laboratory technicians, then replicating them perfectly. That should make stem cell culturing procedures much more reproducible and significantly reduce the cost of deploying new therapies.

A Sticky Problem

Hiromitsu Nakauchi, of Stanford University and the University of Tokyo, described his group’s efforts to overcome a decades-old challenge in stem cell research. Scientists have known for over 25 years that all of the blood cells in a human are renewed from a tiny population of multipotent, self-renewing hematopoietic stem cells. In an animal that’s had all of its hematopoietic lineages eliminated by ionizing radiation, a single such cell can reconstitute the entire blood cell population. This protocol is the basis for several experimental models.

In theory, then, a single hematopoietic stem cell should also be able to multiply indefinitely in pure culture, allowing researchers to produce all types of blood cells on demand. In practice, cultured stem cells inevitably differentiate and die off after just a few generations in culture. Nakauchi and his colleagues have been trying to fix that problem. “After years of hard work, we decided to take the reductionist approach and try to define the components that we use to culture [hematopoietic stem cells],” said Nakauchi.

The team focused on the most undefined component of their culture media: bovine serum albumin (BSA). This substance, a crude extract from cow blood, has been considered an essential component of growth media since researchers first managed to culture mammalian cells. However, Nakauchi’s lab found tremendous variation between different lots of BSA, both in the types and quantities of various impurities in them and in their efficacy in keeping stem cells alive. Worse, factors that appeared to be helpful to the cells in some BSA lots were harmful when present in other lots. “So this is not science; depending on the BSA lot you use, you get totally different results,” said Nakauchi.

Next, the researchers switched to a recombinant serum albumin product made in genetically engineered yeast. That exhibited less variation between lots, and after optimizing their culture conditions they were able to grow and expand hematopoietic stem cells for nearly a month. Part of the protocol they developed was to change the medium every other day, which they found was required to remove inflammatory cytokines and chemokines being produced by the stem cells. That suggested the cells were still under stress, perhaps in response to some of the components of the recombinant serum albumin.

Polyvinyl alcohol can replace BSA in culture medium.

Polyvinyl alcohol can replace BSA in culture medium.

The ongoing problems with serum albumin products led Nakauchi to ask why albumin is even necessary in tissue culture. Scientists have known for decades that cells don’t grow well without it, but why not? While trying to figure out what the albumin was doing for the cells, Nakauchi’s lab tested it against the most inert polymer they could find: polyvinyl alcohol (PVA). Best known as the primary ingredient for making school glue, PVA is also used extensively in the food and pharmaceutical industries. To their surprise, hematopoietic stem cells grew better in PVA-spiked medium than in medium with BSA. The PVA-grown cells showed decreased senescence, lower levels of inflammatory cytokines, and better growth rates.

In long-term culture, Nakauchi and his colleagues were able to achieve more than 900-fold expansion of functional mouse hematopoietic stem cells. Transplanting these cells into irradiated mice confirmed that the cells were still fully capable of reconstituting all of the hematopoietic lineages. Further experiments determined that PVA-containing medium also works well for human hematopoietic stem cells.

Besides having immediate uses for basic research, the ability to grow such large numbers of hematopoietic stem cells could overcome a fundamental barrier to using these cells in the clinic. Current hematopoietic stem cell therapies require suppressing or destroying a patient’s existing immune system to allow the transplanted cells to become established, but this immunosuppression can lead to deadly infections. Transplanting a much larger population of stem cells can overcome the need for immunosuppression, but growing enough cells for this approach has been impractical. Using their new culture techniques, Nakauchi’s team can now produce enough hematopoietic stem cells to carry out successful transplants without immunosuppression in mice. They hope to take this approach into the clinic soon.

Further Readings

Takahashi

Jin Z, Gao M, Deng W, et al.

Stemming Retinal Regeneration with Pluripotent Stem Cells.

Progress in Retinal and Eye Research. 2019;69:38-56.

Maeda, Akiko, Michiko Mandai, and Masayo Takahashi.

Gene and Induced Pluripotent Stem Cell Therapy for Retinal Diseases.

Annual Review of Genomics and Human Genetics. 2019;20.

Nakauchi

van Galen P, Mbong N, Kreso A, et al.

Integrated Stress Response Activity Marks Stem Cells in Normal Hematopoiesis and Leukemia.

Cell Reports. 2018; 25(5):1109-1117.e5.

Nishimura T, Nakauchi H.

Generation of Antigen-Specific T Cells from Human Induced Pluripotent Stem Cells.

Methods in Molecular Biology. 2019;1899:25-40.

Yamamoto R, Wilkinson AC, Nakauchi H.

Changing Concepts in Hematopoietic Stem Cells.

Science. 2018;362(6417): 895-896.

A Developing Field

Speakers

Brigid L.M. Hogan
Duke University School of Medicine

Emmanuelle Passegué
Columbia University Irving Medical Center

Hans Schöler
Max Planck Institute for Molecular Biomedicine

Austin Smith
University of Cambridge

Moderator: Azim Surani
University of Cambridge

Highlights

  • A dramatic transition separates early embryonic stem cells from their descendants.
  • Newly isolated formative stem cells represent an intermediate step in development.
  • Organoids derived from iPS cells provide excellent models for studying human physiology and disease.

In the Beginning

Austin Smith, from the University of Cambridge, gave the final presentation, in which he discussed his studies on the progression of embryonic stem cells through development. In mammals, embryonic development begins with the formation of the blastocyst. In 1981, researchers isolated cells from murine blastocysts and demonstrated that each of them can grow into a complete embryo. Stem cells isolated after the embryo has implanted itself into the uterus, called epiblast stem cells, have lost that ability but gained the potential to differentiate into multiple cell lineages in culture. “So we have two different types of pluripotent stem cells in the mouse, and they’re different in just about every way you could imagine,” said Smith.

Work on other species, including human cells, suggests that this transition between two different types of stem cells is a common feature of mammalian development. The transition from the earlier to the later type of stem cell is called capacitation. To find the factors driving capacitation, Smith and his colleagues looked for differences in gene transcription patterns and chromatin organization during the process, in both human and murine cells. What they found was a global re-wiring of nearly every aspect of the cell’s physiology. “Together these things lead to the acquisition of both germline and somatic lineage competence, and at the same time decommission that extra-embryonic lineage potential,” Smith explained.

Having characterized the cells before and after capacitation, the researchers wanted to isolate cells from intermediate stages of the process to understand how it unfolds. To do that, they extracted cells from mouse embryos right after implantation, then grew them in culture conditions that minimized their exposure to signals that would direct them toward specific lineages. Detailed analyses of these cells, which Smith calls formative stem cells, shows that they have characteristics of both the naive embryonic stem cells and the later epiblast stem cells. Injecting these cells into mouse blastocysts yields chimeric mice carrying descendants of the injected cells in all their tissues. The formative stem cells can therefore function like true embryonic stem cells, albeit less efficiently.

The developmental sequence of pluripotent cells.

The developmental sequence of pluripotent cells.

Post-implantation human embryos aren’t available for research, but Smith’s team was able to culture naive stem cells and prompt them to develop into formative stem cells. These cells exhibit transcriptional profiles and other characteristics homologous to those seen in the murine formative stem cells.

Having found the intermediate cell type, Smith was now able to assemble a more detailed view of the steps in development. Returning to the mouse model, he compared the chromatin organization of naive embryonic, formative, and epiblast stem cells. The difference between the naive and formative cells’ chromatin was much more dramatic than between the formative and epiblast cells.

Based on the results, Smith proposes that naive embryonic stem cells begin as a “blank slate,” which then undergoes capacitation to become primed to respond to later differentiation signals. The capacitation process entails a dramatic change in the cell’s transcriptional and chromatin organization and occurs around the time of implantation. “We think we now have in culture … a cell that represents this intermediate stage and that has distinctive functional properties and distinctive molecular properties,” said Smith. After capacitation, the formative stem cells undergo a more gradual shift to become primed stem cells, which are the epiblast stem cells in mice.

Smith concedes that the human data are less detailed, but all of the experiments his team was able to do produced results consistent with the mouse model. Other work has also found corroborating results in non-human primate embryos, implying that the same developmental mechanisms are conserved across mammals.

Organoid Recitals

After the presentations, a panel consisting of members of the Innovators in Science Award’s Scientific Advisory Council and Jury took the stage to address a series of questions from the audience.

The panel first took up the question of how researchers can better study human stem cells, given the ethical challenges of working with embryos. Brigid Hogan described organoid cultures, in which researchers stimulate human iPS cells to grow into minuscule organ-like structures. “This is a way of looking at human development at a stage when it’s [otherwise] completely inaccessible,” said Hogan. Other speakers concurred, adding that implanting human organoids into mice provides an especially useful model.

Another audience member asked about the potential for human stem cell therapy in the brain. Hogan pointed to the use of fetal cells for treating Parkinson’s disease as an example, but panelist Hans Schöler suggested that that could be a unique case. Patients with Parkinson’s disease suffer from deficiency in dopamine-secreting neurons, so implanting cells that secrete dopamine in the correct brain region may provide some relief.

Panelists also addressed the use of stem cells in regenerative medicine, where researchers are targeting the nexus of aging, nutrition, and brain health. Emmanuelle Passegué explained that the body’s progressive failure to regenerate itself from its own stem cells is a hallmark of aging. “I think we are getting to an era where transplantation or engraftment [of cells] will not be the answer, it will really be trying to reawaken the normal properties of the [patient’s own] stem cells,” said Passegué.

As the meeting concluded, speakers and attendees seemed to agree that the field of stem cell research, like the cells themselves, is now poised to develop in a wide range of promising directions.

Further Readings

Smith

Dunn SJ, Li MA, Carbognin E, et al.

A Common Molecular Logic Determines Embryonic Stem Cell Self-Renewal and Reprogramming.

The EMBO Journal. 2019;38(1).

Kalkan T, Bornelöv S, Mulas C, et al.

Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.

Cell Stem Cell. 2019;24(5):785-801.e7.

Mulas C, Kalkan T, von Meyenn F, et al.

Defined Conditions for Propagation and Manipulation of Mouse Embryonic Stem Cells.

Development. 2019:146(6).

Foreign-Born Scientists Advancing New Discoveries

The Blavatnik Family Foundation and The New York Academy of Sciences recently announced 31 finalists for the 2019 Blavatnik National Awards for Young Scientists in chemistry, physical sciences & engineering, and life sciences.

Published June 20, 2019

By Kamala Murthy

60% of Blavatnik Awards honorees are immigrants to the country in which they were recognized (U.K., U.S., Israel)

This year, many finalists are foreign-born, continuing a long history of the U.S. providing academic opportunity to large numbers of scientists and engineers from abroad. These finalists are now working on advances across multiple disciplines that are destined to impact populations around the world.

Here, some of the finalists discuss their journey, what inspired them to come to the U.S., and how their contributions will impact science for decades to come.

Dr. Jure Leskovec

Dr. Jure giving a talk at Stanford

Dr. Jure Leskovec, Associate Professor, Stanford University is a finalist for developing machine-learning methods to predict safety and potential adverse side effects of pharmaceuticals.

“It felt very real.” That’s how Jure Leskovec describes his first visit to Silicon Valley in 1998.

As a 17-year-old boy from Slovenia, he was fascinated to see such a large swath of high-tech companies in one area, and he felt privileged to step inside labs that were conducting cutting-edge research and producing the world’s most innovative products.

“I instantly knew that I had to be a part of this,” he said.

Leskovec went on to earn a doctorate in machine learning (the scientific study of algorithms and statistical models that computer systems use to perform a task without using explicit instructions) from Carnegie Mellon University and received post-doctoral training at Cornell University.

Today, he holds dual citizenship in the U.S. and Slovenia, and is a full-time, assistant professor of computer science at Stanford University while also acting as the chief scientist at Pinterest.

Dr. Jure giving a talk at Jozef Stefan Institute in Slovenia

Reflecting on his journey, Leskovec said he wanted to train at a university that offered the best machine-learning research program and go back to Slovenia once it was complete. But the opportunities and support he received in the U.S. kept pulling him back until he finally decided to settle here.

He is grateful for that and wants to do the same for other deserving students. He founded the American Slovenian Education Foundation that works to unite Slovenian scholars and educators globally and grants fellowship to talented Slovenian undergraduates.

“Living in the U.S. opened my mind and helped me appreciate the diversity of our world,” he said.

Leskovec and his team are building an artificial intelligence system for predicting, not simply tracking, potential side effects from drug combinations. This could help physicians make better decisions about what drugs to prescribe, help researchers find better combinations of drugs to study complex diseases and assist the FDA in its drug approval process.

His research also will help regulators overcome what he described as a long and complex recall process.

“Outside of a clinical study, the way we learn more about a drug’s potential side effects is to have patients report their experience to their physician, the manufacturer or directly to the FDA,” Leskovec said.

“Depending on the number of reports or the severity of the side effect, the FDA may ask the manufacturer to investigate. Once the investigation is completed, the FDA may consider new labeling, or even have the drug removed from the market.”

Dr. Andrea Alù

Dr. Alù giving a lecture at the Advanced Science Research Center at CUNY (photo credit ASRC, CUNY)

Dr. Andrea Alù, Professor, City University of New York (CUNY) is a finalist for leading breakthrough research in metamaterials with exotic optical and acoustic properties, including scattering suppression, giant nonlinearities and nonreciprocity.

During his undergraduate studies in Rome, Andrea Alù won a competition to visit the U.S. for a research internship at University of Pennsylvania (UPenn). Once the internship was complete, he returned to Rome to earn his doctorate, but the pull of opportunity in the U.S. brought him back to finish his post-doctoral studies at UPenn.

“My first trip to the U.S. and the opportunity to work in complete freedom with my research mentor, Professor Engheta, during my internship at UPenn had a profound impact on my life,” Alù said.

“I got the opportunity to get myself immersed in an up and coming research area with tremendous opportunities and work with the top scientists in the field. I knew I wanted to come back and do advanced research here in the U.S. and am glad I made that decision.”

Alù’s decision has proven to be a great success. His research team is implementing new concepts for sensors that provide enhanced sensitivity and resolution for biomedical devices and have been collaborating with groups working on brain and health issues to build better ways of sensing and imaging.

Dr. Alù receiving the Alan T. Waterman Award in 2015

Alù is also actively working to improve the technology that makes computing faster, more accurate and helps create more energy efficient devices.

He believes the use of light instead of electrons in working with quantum regime can enhance computing dramatically. And that would help to meet energy needs to operate IT infrastructure in a more sustainable manner.

Alù’s work has received international attention. Among his numerous awards, one that stands out is being named a Vannevar Bush Faculty Fellow – the department’s most prestigious single-investigator award that aims to advance transformative, university-based fundamental research.

“This is a country that welcomes talent from other countries and gives them the opportunity to live their best lives and do their best work,” Alù said.

He now holds dual citizenship in the U.S. and Italy.

Dr. Mohammad R. Seyedsayamdost

Dr. Seyedsayamdost during his postdoc at Harvard Medical School

Dr. Mohammad R. Seyedsayamdost, Assistant Professor, Princeton University is a finalist for exploring ways to extract hidden drug-like molecules encoded in bacteria that can be used to address the global shortage of antibiotics.

It was the peak of the Iran-Iraq war in 1987 when Mohammad Seyedsayamdost’s family fled from Iran to Germany. He was eight years old.

“The trigger for my parent’s life-changing decision came when a hospital right next to my elementary school was bombed,” he said.

Since then, Seyedsayamdost has lived in three countries – Germany, Australia and the U.S.

Growing up in a family where education was prioritized, Seyedsayamdost always wanted to come to the U.S. for his higher education. He attended Brandeis University in Massachusetts for his undergraduate studies and ultimately received his doctorate in Chemistry under the guidance of Professor JoAnne Stubbe at MIT, followed by postdoctoral work at Harvard Medical School with Professor Jon Clardy and Professor Roberto Kolter.

“Every step of the way, I missed my family and wanted to return home. But I also knew the best way to honor the sacrifices my parents made for my future was to do exceptional work that would create a positive impact in the world,” he said.

Dr. Seyedsayamdost during middle school in Australia

Seyedsayamdost is working on a groundbreaking method for accessing a previously hidden realm of drug-like molecules encoded in bacteria called secondary metabolites.

Genome sequencing has shown that most biosynthetic genes that produce these metabolites are not expressed under normal laboratory conditions. But Seyedsayamdost’s method, called High Throughput Elicitor Screening (HiTES), unlocks these novel compounds, some of which have shown much enhanced bioactivity.

He and his research team at Princeton University are using this method to isolate novel antibiotic molecules, which could help develop antibiotics to meet market shortages.

“A high risk, high reward kind of study” is how he describes his work.

Like his fellow scientists, Seyedsayamdost is thankful for the opportunities he received studying and working in the U.S. and plans to apply for citizenship when he is eligible in four years.

“One thing I have always appreciated about science in the U.S. is that it provides an even playing field,” he said.

“Once you are in, you are judged by your talent and capabilities and not by where you are from or the color of your skin. The can-do attitude and the innovative mindset of people in this country, is what makes it so desirable for the world’s best scientists to come here and do their best work.”

To learn more about the Blavatnik Awards for Young Scientists, visit blavatnikawards.org.

The 2019 Blavatnik Awards for Young Scientists National Laureates

A shot from the Academy's 2019 Blavatnik Award ceremony.

Our showcase of the inspiring honorees breaking new ground in life sciences, chemistry and physical sciences.

Published May 1, 2019

By Carina Storrs, PhD

Life Sciences Laureate

Heather J. Lynch, PhD, Stony Brook University

A pursuit of penguins leads to new territories in technology

It may be hard for penguin enthusiasts to believe, yet Heather Lynch PhD says the “most fun part of the entire year” is not the four months a year she and her team spend in Antarctica, but rather the time spent pouring over the reams of data when she returns. Lynch was originally drawn to penguins as a post-doc at the University of Maryland because of the challenge of studying them.

Lynch, now an Associate Professor at Stony Brook University, is tackling the fundamental questions of how many penguins are there and where exactly are they? Those may seem like simple questions, but they are stymied by data shortcomings, such as not having precise location data from on-the-ground surveys of the flightless, tuxedo-donning birds.

To subvert the treacherous Antarctic environment, Lynch turned to the wealth of NASA satellite imagery of the Antarctic that dates back decades. She and a colleague developed algorithms that scan the thousands of coastal images for signs of penguins revealed by their pink-hued guano (bird feces). Then, when they get tipped off to the presence of a large colony of penguins, they bring glacial-ready drones to the areas to take high-resolution pictures for exact headcounts.

The Adélie penguins

One of the biggest finds was a supercolony of about 1.5 million Adélie penguins on the Danger Islands right off the tip of the Antarctic Peninsula, which stretches toward South America. No one knew this colony existed — Lynch didn’t believe the algorithm at first, until she could confirm it with other satellite imagery.

She and her lab have also discovered much smaller colonies of chinstrap and gentoo penguins on the nearby Aitcho Islands. Without Lynch’s mathematical techniques and use of satellite technologies to detect guano, these colonies of penguins may have never been discovered.

Thanks to this multi-pronged approach, Lynch can now pride herself on the ability to locate nearly all of the penguin colonies in the Antarctic and is excited about the possibility of discovering even more colonies. Lynch’s game-changing ability to apply mathematical modeling to ecological data collected from satellites, aerial drones and field work is what earned her the title of 2019 Blavatnik National Awards Laureate in Life Sciences.

Lynch has always had one foot in the technological side. She was close to getting her PhD in physics when she “came up for air,” decided she wanted to apply her problem-solving zest toward environmental issues, and switched to a PhD program in biology.

Developing Skills in Statistics and Programming

However, she thinks the expertise that she acquired in mathematical modeling while working on her physics PhD has been the secret to her success. She advises students interested in pursuing any STEM field to develop some statistical and programming abilities.

“[They] are that all-access pass,” Lynch says. “There is not a lab on the planet that does not need people with those skills.”

Although Lynch’s discoveries have been welcome news for ecologists and penguin lovers alike, they can appear to belie the peril facing these birds due to climate change.

“All of these other populations, even other Adélie penguins, are crashing,” Lynch says.

A big part of her research focuses on developing models to understand why the Danger Island colony is flourishing, while the Adélie penguins on the western side of the Antarctic Peninsula are declining.

Implications for Conservation and the Impact of the Award

It almost goes without saying that Lynch’s research has implications for conservation.

“When we found the Danger Island populations, the first email I sent was to the people who were designing the Marine Protected Area in the region,” Lynch recalls. The Danger Islands had not been considered an important area to protect, but in what Lynch calls a “dream scenario,” policy makers expanded the area to include the islands after she told them about the Adélie supercolony.

Lynch is excited that the Blavatnik Award will bring attention to the recent technological advances in the field of ecology. The synergistic effects of Lynch’s methods will have a wide-ranging and critical impact in the fields of ecology and conservation biology in the face of impending, human-induced mass extinctions. Lynch and her lab have already expanded her methods to evaluate Antarctic seal and whale populations, and scientists can use her methods in the hope of saving other species all over the world.

Chemistry Laureate

Emily Balskus, PhD, Harvard University

Cracking the mysteries of the human microbiome

The first time that Emily Balskus, PhD worked with a microbiome, the term for communities of bacteria that live in our bodies and all around us, she was knee-deep in the salt marshes off the southern coast of Cape Cod, collecting bacteria.

Things got pretty messy, but the experience helped convince Balskus — who was then conducting postdoctoral research in chemical biology at Harvard Medical School — that she wanted to bring her chemistry expertise to bear on the biggest questions about the human microbiome.

Up until those marshy waters, Balskus was doing, as she puts it, “pretty conventional” chemistry. But early on during her postdoctoral training she attended a seminar about the Human Microbiome Project, which would set out to catalogue the microbes living on and within us. It opened her eyes to the shocking fact that scientists knew almost nothing about what these bacteria were actually doing, and how they affected our health.

“I couldn’t believe that we could be living so closely with so many microbes, that we had shared evolutionary history with them, and there was so much we didn’t know about them,” Balskus recalls.

Understanding the Microbiome in our Gut

Much of what we now know about the goings-on of the microbiome in our gut — for example, how certain bacterial residents can increase the risk of heart disease or thwart the activity of the medications we take — is thanks to the research group that Balskus has been leading at Harvard University since 2011.

For her work getting to the bottom of microbial mysteries, Balskus was named the 2019 Blavatnik National Awards Laureate in Chemistry, which Balskus says is “wonderful” and “very humbling.”

One of the most exciting discoveries of the Balskus lab is connecting how bacteria in the gut microbiome may increase the risk of colorectal cancer. It had been known for more than a decade that certain strains of Escherichia coli (E. coli) make a toxic molecule, called colibactin, and that these bacterial strains are more likely to be found in the gut of people with colorectal cancer.

Understanding the Chemical Components

Balskus and her team focused on determining the chemical makeup of the mysterious colibactin molecule, which had been challenging for other chemists to isolate and characterize. The difficulty of studying this molecule using more conventional approaches made her consider whether her unique perspective might provide another path.

Balskus’ team explored how colibactin was produced in the gut without knowing its complete structure. They eventually discovered that the colibactin molecule contains a structure called a cyclopropane ring, which is known to cause DNA damage that can lead to cancer-causing mutations. Importantly, her team showed that exposing human cells in the lab to the toxic E. coli strain led to a specific type of cyclopropane-dependent DNA damage, whereas cells exposed to harmless strains of E. coli showed no signs of similar DNA damage.

In future studies, she hopes to determine whether this type of DNA damage can be seen in cells obtained from biopsies of colorectal cancer patients, to confirm whether this toxic E. coli is indeed responsible for increasing cancer risk.

Balskus credits her postdoctoral advisor, Christopher Walsh, MD, PhD for suggesting she take the fateful trip to the salt marshes, which was part of a summer microbiology course held at the Marine Biological Laboratory in Woods Hole, Mass. This course equipped her with the tools of microbiology and expertise that she continues to use to probe the human microbiome.

Combining Chemistry and Microbiome Research

Today, Balskus is a Professor of Chemistry and Chemical Biology at Harvard University, and a leader in bringing the worlds of chemistry and microbiome research together. This spring she helped organize the first scientific conference on the chemistry of the human and other microbiomes.

“Both [fields] are very excited about this intersection,” Balskus says. She is also venturing into other scientific fields, such as genetics, and exploring how chemistry’s tools can advance other areas of biological research.

Balskus hopes to use the Blavatnik Award funds to promote women and other underrepresented groups in science. She recognizes how much her female science teachers at the all-women’s high school and the small liberal arts college she attended encouraged her and were role models for her. Many young women are not so fortunate.

“It is not one thing that makes it hard, it is a bunch of things that make it difficult for women to feel like they belong in science,” Balskus says.

Physical Sciences & Engineering Laureate

Ana Maria Rey, PhD, University of Colorado Boulder

Building the world’s most precise atomic clock

Ana Maria Rey, PhD fell for physics in high school, the moment she realized she could use mathematical equations to predict how a ball will move. It was an easy love affair, as Rey flew through physics problems for fun.

But at the university she attended in her native Colombia, a professor challenged the students with such long physics exams that students had no time to perform detailed calculations. This professor, who Rey considers her first role model, taught them to rely on intuition instead, which could only be acquired through intensive study of the subject.

It is a lesson that Rey has carried with her throughout her career. Over the course of her PhD studies at the University of Maryland, through two periods of postdoctoral training, and now as a Professor of Physics at the University of Colorado Boulder, Rey has delved deep into the world of quantum mechanics.

Diving into Quantum Mechanics

Quantum mechanics describes the behavior of the smallest particles of matter: the atoms and sub-atomic particles that make up balls and every other material on Earth. Just like her early days with physics, Rey is explaining the behavior of the quantum world using mathematical models. But now she is the one developing the models, in groundbreaking work that earned her the honor of being named the Blavatnik National Awards Laureate in Physical Sciences & Engineering this year.

“Understanding [atomic and sub-atomic] behavior is really, really important because it can lead to technological development,” Rey says.

Although her research is theoretical, its applications are tangible and far-ranging, from creating GPS (global positioning system) that can provide more accurate location data and quantum computers that would be thousands of times faster than today’s machines, to ultimately enabling the direct measurement of gravitational waves, which are ripples in the so-called fabric of the universe.

Building a More Precise Atomic Clock

At the heart of all these possibilities, and the crux of Rey’s models, is the ability to build a more precise atomic clock, which can measure much smaller units of time than modern clocks — as short as one billionth of a billionth of a second. As Rey explains, the pendulum of an atomic clock is laser light, and the thing that measures each swing of the pendulum is atoms.

The problem that scientists have to understand, and ideally control, is how the atomic timekeepers move when they are zipping around and colliding with each other. Because of Rey’s equations, they are getting closer to that goal. She credits the physicists she collaborates closely with at JILA, where she is a Fellow, for conducting the breakthrough experiments with ultra-cold atoms trapped by lasers, making them slower and easier to track, for informing her calculations.

Rey says the funding and recognition that come with the Blavatnik Award will allow her to push farther into what she calls “the most exciting part of the work.” Although her team has already given the world its most precise atomic clock, that is nothing compared to what they could achieve if they could entangle, or link together, atoms in such a way that they behave as one unit.

Entanglement, which has been shown by allowing atoms to interact and then separating them, would eliminate the noise that throws off atomic clocks.

“This is the holy grail,” Rey says, adding that, “we should be able to see what the universe is made of,” such as mysterious dark matter.

Driven By Passion

Rey believes the key to her success in theoretical physics is loving what she does and working hard at it.

“Things are not going to come to you. You might be very smart, but I don’t think it’s enough,” Rey says.

Her other great role model, renowned JILA fellow, Deborah Jin, PhD, who passed away in 2016, showed Rey that it is possible to have a successful scientific career and a happy family life, and generally to be there for people. Rey, who was also selected as a MacArthur Fellow in 2013 and the MOSI Early Career National Hispanic Scientist of the Year in 2014, says “I hope in some way, I can share the same type of help with young women scientists.”

The 2019 Blavatnik National Awards for Young Scientists Ceremony

2019 Blavatnik Award winners in Israel and the UK

A group of Blavatnik Award winners pose together for a photo.

Meet the rising stars who are receiving recognition for their ground-breaking research.

Published May 1, 2019

By Robert Birchard

2019 Blavatnik Award Laureates, Israel

Life Sciences Laureate

Michal Rivlin, PhD, Senior Scientist and Sara Lee Schupf Family Chair, Weizmann Institute of Science

Dr. Michal Rivlin is a neuroscientist who has made the paradigm-shifting discovery that cells in the adult retina can exhibit plasticity in their selectivity and computations. One of the first demonstrations of neuronal plasticity outside the brain, this raises fundamental questions about how we see, and has implications for our understanding of the mechanisms underlying computations in neuronal circuits, the treatment of retinal diseases, blindness and development of computer vision technologies.

Chemistry Laureate

Moran Bercovici, PhD, Associate Professor, Faculty of Mechanical Engineering, Technion – Israel Institute of Technology

Dr. Moran Bercovici is an analytical chemist who studies microscale processes coupling fluid mechanics, electric fields, heat transfer and chemical reactions. His studies have potential implications in multiple fields, ranging from the detection of low concentrations of biomolecules for rapid and early disease diagnostics, to the creation of new microscale 3D printing technologies.

Physical Sciences & Engineering Laureate

Erez Berg, PhD, Associate Professor, Weizmann Institute of Science

Dr. Erez Berg is a theoretical condensed matter physicist who develops novel theoretical and computational tools to study long-standing and emerging questions in quantum materials. His research has provided important insights into the physics principles behind a wide variety of exotic phenomena in quantum materials, which will help to speed up the implementation of these materials in next generation electronics including quantum computing, magnetic resonance imaging and superconducting power lines.

2019 Blavatnik Award Honorees, United Kingdom

Physical Sciences & Engineering Laureate

Konstantinos Nikolopoulos, PhD, Professor of Physics, University of Birmingham

Experimental particle physicist, Prof. Konstantinos Nikolopoulos led a 100-physicist subgroup in ATLAS, a large scientific collaboration at CERN, which made key contributions to the discovery of the Higgs boson. This discovery, jointly announced by the ATLAS and CMS collaborations at CERN, is regarded as one of the biggest breakthroughs in fundamental physics this century. This discovery completed the experimental verification of the Standard Model of particle physics, the mathematical theory through which we understand nature at the fundamental level, and resulted in the Nobel Prize in Physics being awarded to the physicists who predicted the Higgs boson decades ago. Prof. Nikolopoulos’ work has significantly improved our understanding of the Higgs boson and explored potential new physics beyond the Standard Model.

Physical Sciences & Engineering Finalists

Gustav Holzegel, PhD, Professor of Pure Mathematics, Imperial College London

Prof. Gustav Holzegel is a mathematician, who develops rigorous mathematical proofs of physics questions related to Einstein’s general theory of relativity. He provided the first proof of a decades-old conjecture about the stability of black holes in the case of the simplest form of black holes in the universe, and has made significant progress towards completely proving this conjecture in the cases of more complicated types of black holes. The techniques he developed have also influenced the studies on other open fundamental questions in theoretical physics and astrophysics.

Máire O’Neill, PhD, Professor of Information Security; Principal Investigator, Centre for Secure Information Technologies; Director, UK Research Institute in Secure Hardware and Embedded Systems, Queen’s University Belfast

Prof. Máire O’Neill is an electrical engineer working in the area of cybersecurity. She has proposed novel attack-resilient computer hardware platforms and chip designs that have found immediate applications. Her solutions are orders of magnitude faster than prior security implementations while also being cost effective. Her achievements have already generated an enormous impact on society, which will continue to increase as cyberattacks costing the global economy hundreds of billions of dollars annually, continue to grow at an unprecedented scale.

Chemistry Laureate

Philipp Kukura, PhD, Professor of Chemistry, University of Oxford

Prof. Kukura is a physical chemist who is developing cutting-edge optical methodologies for the visualisation and analysis of molecules such as proteins that exist within the body. To accomplish this task, he takes advantage of the scattering of visible light, which is the universal process through which we see the world around us. On the macro-scale, this scattered light provides information on the size and shape of an object. What Prof. Kukura has shown is that when driven to the extreme by detecting this light scattering from tiny objects in a microscope, this approach not only works with single biomolecules, but can also be used to measure their molecular mass, introducing a new way of weighing objects. The macroscopic equivalent would be to know the mass of a loaf of bread to within a few grams just by looking at it. Prof. Kukura hopes that this approach will be used widely to discover how biomolecules assemble, interact and thus function, as well as understand what goes wrong in disease, and how it can be addressed at a molecular level.

Chemistry Finalists

Igor Larrosa, PhD, Professor of Organic Chemistry,
The University of Manchester

Organic chemist, Prof. Igor Larrosa is a world-leader in a sub-field of organic chemistry called carbon-hydrogen bond activation, which is focused on finding ways to make these normally stable bonds reactive. Specifically, he has established new mechanistic insights into how C–H bonds can react with transition metals, and developed novel catalysts for the facile construction of molecules that previously were only accessible through multistep organic transformations.

Rachel O’Reilly, PhD, Chair of Chemistry & Head,
School of Chemistry, University of Birmingham

Prof. Rachel O’Reilly is a polymer chemist that has pioneered the use of innovative chemical approaches in the fields of DNA nanotechnology, sequence-controlled synthesis of polymers and precision synthesis to foster the development of novel materials. The novel molecules and structures produced from these methodologies have potential applications in healthcare, energy-related fields and sustainable chemistry.

Life Sciences Laureate

Ewa Paluch, PhD, Chair of Anatomy, University of Cambridge; Professor of Cell Biophysics, MRC Laboratory for Molecular Cell Biology, University College London

Prof. Ewa Paluch’s novel discoveries are at the forefront of cell biology: she has elucidated key biophysical mechanisms of cell division and migration, and has established physiological roles of cellular protrusions known as “blebs.” Previously thought to exist only in sick or dying cells, she established that these protrusions on the cell surface are common in healthy cells, and that blebs have important functions in cell movement and division. Her work will influence treatment for diseases such as cancer, where cell shape and migration are key to disease pathology, and she is leading the field towards a complete understanding of how the laws of physics affect the behavior of cells.

Life Science Finalists

Tim Behrens, DPhil, Deputy Director, Wellcome Centre for Integrative Neuroscience, University of Oxford; Professor of Computational Neuroscience, University of Oxford; Honorary Lecturer, Wellcome Centre for Imaging Neuroscience, University College London

Prof. Timothy Behrens is a neuroscientist whose work has uncovered mechanisms used by the human brain to represent our world, make decisions and control our behavior. An understanding of how our neurons function in networks to control behavior is fundamental to our understanding of the brain, and has implications for neural network computing, artificial intelligence and the treatment of mental and cognitive disorders.

Kathy Niakan, PhD, Group Leader, The Francis Crick Institute

Dr. Kathy Niakan is a developmental biologist conducting pioneering research in human embryonic development, elucidating early cell-fate decisions in embryonic cells. To further these studies, she became the first person in the world to obtain regulatory approval to use genome-editing technologies for research in human embryos. Her research may provide new treatments for infertility and developmental disorders, and her work in scientific policy and advocacy is defining the ethical use of human embryos and stem cells in scientific research.

2019 Blavatnik Award Honorees, United Kingdom

2019 Blavatnik UK Awardees Are Bettering the World

A shot from the awards ceremony for the Blavatnik Award.

Learn more about the ceremony that celebrated this year’s Blavatnik Awards for Young Scientists in the United Kingdom.

Published May 1, 2019

By Kamala Murthy

The Blavatnik Family Foundation hosted its annual ceremony celebrating the honorees of the 2019 Blavatnik Awards for Young Scientists in the United Kingdom at the Victoria and Albert Museum (V&A) in London.

The Ceremony was attended by members of the UK’s scientific elite as well as key figures within the fields of government, academia, business and entertainment. Neuroscientist and 2014 Nobel Laureate Professor John O’Keefe of University College London, served as the Master of Ceremonies for the evening.

“The Blavatnik Awards are given not just for exceptional work already done, but in support of world-changing work that we believe is yet to be done by these young scientists,” says O’Keefe.

Academy President and CEO Ellis Rubinstein also gave remarks thanking the support of the scientific community within the United Kingdom and complimenting the outstanding group of scientists that make up the Blavatnik Awards’ UK Jury and Scientific Advisory Council.

Among the Most Dedicated and Original Thinkers in their Spheres

In commenting on the caliber of the nine honorees, Prof. O’Keefe mentioned “the young scientists and engineers are among the most dedicated and original thinkers in their spheres in the United Kingdom…They are making headlines across medical and tech communities for discoveries and innovations in human development and cognition; from novel ways to synthesize drugs and sustainable polymers, to advances in cybersecurity and radical breakthroughs in fundamental physics.”

In each scientific category (Chemistry, Physical Sciences & Engineering, Life Sciences), two Finalists were each awarded prizes of US$30,000, and one Laureate in each category was awarded US$100,000. The Awards’ founder, Sir Leonard Blavatnik, presented medals to the three Laureates and six Finalists at the ceremony.

Throughout the course of the evening, the audience watched three films featuring the honorees from the three Award categories. The ceremony concluded with a fireside chat and the Blavatnik Awards tradition of making a “Toast to Science.”

Learn more about the 2019 Blavatnik Awards ceremony in the UK here.

UK Blavatnik Awardees Are Bettering the World

From cybersecurity and genome-editing to unraveling the mysteries of the atom and deciphering the complexities of the human brain, these nine young scientists are making a positive impact on our world.

Published May 1, 2019

By Kamala Murthy

The Laureates and Finalists of the 2019 Blavatnik Awards for Young Scientists in the United Kingdom are shaping the future of science. 

A distinguished jury of leading UK senior scientists and engineers selected the nine 2019 Blavatnik Awards honorees from 83 nominations submitted by 43 academic and research institutions across England, Northern Ireland, Scotland, and Wales, as well as the Awards’ own Scientific Advisory Council.

These young scientists and engineers are already making headlines across the UK’s scientific community for discoveries and innovations in research ranging from the mechanics of human cells to new ways to weigh biomolecules, advances in cyber security and radical breakthroughs in fundamental physics. Their discoveries are transforming our understanding of the world and improving human lives.

One Laureate from each of the three categories of Life Sciences, Physical Sciences & Engineering, and Chemistry will receive an unrestricted prize of $100,000 — one of the largest unrestricted prizes available to early-career scientists in the UK.

2019 Life Sciences Laureate

Prof. Ewa Paluch, University College London (UCL) and University of Cambridge

2019 Chemistry Laureate

Prof. Philipp Kukura, University of Oxford

2019 Physical Sciences & Engineering Laureate

Prof. Konstantinos Nikolopoulos, University of Birmingham

2019 Blavatnik Awards in the UK Finalists

Two Finalists in each of the following categories will receive unrestricted prizes of $30,000 each.

Life Sciences

Prof. Timothy Behrens, University of Oxford; honorary Principal Investigator, University College London (UCL)

Dr. Kathy Niakan, The Francis Crick Institute

Chemistry

Prof. Igor Larrosa, The University of Manchester

Prof. Rachel O’Reilly, University of Birmingham

Physical Sciences & Engineering

Prof. Gustav Holzegel, Imperial College London

Prof. Máire O’Neill, Queen’s University Belfast

“Last year, our first year of administering the Blavatnik Awards for Young Scientists in the United Kingdom, we were touched by the reaction of leaders of the UK’s scientific community who agreed that there is no other prize in the UK that honors the achievements and, most especially, future promise of young scientists,” said Ellis Rubinstein, President and CEO of The New York Academy of Sciences and Chair of the Awards’ Scientific Advisory Council. “On behalf of our global Academy we have been thrilled to see so many institutions recognized through their fantastic honorees. And we are enormously proud to collaborate with the UK’s esteemed jury and Scientific Advisory Council members.”

The 2019 Blavatnik Awards Laureates and Finalists in the UK will be honored at a gala dinner and ceremony at the prestigious Victoria and Albert Museum in London on March 6, 2019. The following day, the honorees will present their research in a symposium open to the public entitled “Cure, Create, Innnovate: 9 Young Scientists Transforming Our World,” to be held at the Science Museum, London—a free event to all Academy Members.

To learn more about the Blavatnik Awards and its cohort of Awards programs in the US, UK and Israel please visit the Blavatnik website here.

Tapping into the Potential of Regenerative Stem Cells

A healthcare worker comforts a patient.

The Honorees of the 2019 Innovators in Science Award are tapping the potential of stem cells.

Published May 1, 2019

By Hallie Kapner

Stem cells are the ultimate asset in the body’s efforts to heal damage and repair wounds. These powerhouses of regeneration are responsible for maintaining the integrity of skin, bone and other tissues. The 2019 Innovators in Science Award, sponsored by Takeda Pharmaceuticals, recognizes two outstanding researchers in the field of regenerative medicine. The Senior Scientist and Early-Career Scientist winners are advancing our understanding of the miraculous inner work­ings and remarkable healing powers of stem cells.

Turning Stem Cell Research into Life-Saving Therapies

Michele De Luca, MD

Michele De Luca, MD, first encountered epithelial stem cells in the 1980s, during a research fellowship at Harvard Medical School in the lab of stem cell therapy pioneer Howard Green.

“I fell in love with the concept, the cell type, and the system,” he said, describing how the thrall of regenerative medicine — then in its infancy — would come to dominate the next thirty years of his career.

De Luca, winner of the Senior Scientist Award and director of the Center for Regenerative Medicine “Stefano Ferrari” at the University of Modena and Reggio Emilia in Modena, Italy, has made fundamental discoveries in the molecular and genetic characteristics of epithelial stem cells, translating those findings into therapies that change and save patients’ lives.

De Luca’s earliest clinical triumphs in skin regeneration were in the treatment of burn patients. Using the patient’s own epidermal stem cells, De Luca grew skin grafts in culture, then successfully used them to repair large lesions. In collaboration with Graziella Pellegrini, professor of cell biology at the University of Modena and Reggio Emilia, De Luca went on to pioneer new stem cell culture and grafting techniques, ultimately developing the first corneal regenerative therapy, Holoclar, which utilizes limbal stem cells to generate healthy corneal tissue for patients who have sustained chemical burns or other ocular injuries. The technique, which can restore lost sight in some cases, was approved by the European Medical Agency as a commercial stem cell therapy in 2015.

Decades of research, experimentation, and clinical trials prepared De Luca well for the day (later that same year) when he first learned of a seven-year-old boy in Germany suffering from a debilitating and often fatal skin condition, junctional epidermolysis bullosa, which is caused by a genetic mutation. Working against the clock, De Luca and a team of collaborators in Modena and Germany attempted a highly experimental epithelial stem cell gene therapy.

The team used a retroviral vector to introduce a functional copy of the mutated gene into the patient’s stem cells, then rapidly grew healthy sheets of skin for transplantation. Three years later, the transgenic skin grafts remain symptom-free. De Luca noted that his case has provided critical insights into epidermal stem cell biology and the potential for using gene therapy for other skin conditions.

“To me, this is the essence of regenerative medicine, and this is the future,” he said.

Decoding the “Crosstalk” Between Epithelial Stem Cells and the Immune System

Shruti Naik, PhD

Shruti Naik, PhD, assistant professor in the departments of pathology, medicine, and dermatology at NYU School of Medicine and winner of the Early-Career Scientist Award, is exploring the interplay between immune cells, stem cells, and resident microbes in epithelial tissues.

By eavesdropping on what she describes as a “vital conversation” between these groups, Naik hopes to better understand how their interplay with each other — and with the external environment — facilitates healing and regeneration. Her work is also providing insight into the devastating conditions that can result when these systems break down, such as non-healing wounds and ulcers.

Naik’s work aims to systematically decode the dialogue among various cell communities within barrier tissues as they encounter and respond to external stimuli or injury, with a particular focus on the role of epithelial stem cells, which play pivotal yet poorly understood roles in the body’s defensive and regenerative processes. Naik’s research has revealed surprising sensitivities and attributes of these cells.

“Stem cells are actually exquisite sensors of inflammation, and we’ve discovered that they can even remember inflammation and change their behavior accordingly,” she said.

This cellular memory can promote healing by “tuning” the stem cells to respond and regenerate tissue more quickly.

Understanding which immune signals modulate the activity of stem cells, and how the microbial communities of the skin, lung, and gut can influence the process of tissue repair, may lead to new therapeutic approaches for chronic ulcers and other wounds.

“We’re really at the beginning of a new era of understanding how stem cells sense inflammatory and stress signals and incorporate them into generating new tissues,” Naik said.

Overcoming Doubts with Help from Role Models

A woman smiles for the camera.

It was a life-changing physics teacher and her own ability to overcome doubt that played a significant role in the nanotechnology adventure of Alexandra Boltasseva.

Published February 1, 2019

By Alexandra Boltasseva, PhD

Alexandra Boltasseva, PhD

I was born in Kanash, a small town on the Southern route of the famous Trans-Siberian Railway in modern day Russia. Being from a small town in the middle of nowhere, one of the first questions I’m often asked is how I got into science. I have often repeated the same answer: “I have always been fascinated by technology and devices.” But the truth is that I have always been fascinated by a much simpler thing – the world around me.

All my life I was blessed to have the most devoted and inspirational people around me. As every child, I loved to come to my parents’ work. Both engineers, my parents worked for railway-related organizations. My mom has a degree in applied mathematics and was on the team who installed the very first computer at the local train repair plant. My dad was the head of a small radio communications laboratory that controlled train communication lines between two of the nearest cities – Nizhnyi Novgorod and Kazan. At his lab, I loved playing with colorful resistors and wondered what they actually did while flipping through Rudolf Svoren’ book Electronics: Step by Step.

A Life-changing Teacher

In middle school, my life changed because of my physics teacher Valery V. Gorbenko. His true love for physics and devotion to his students opened up a world beyond my small-town school. I joined his after-school physics classes, and soon after participated and won the physics Olympics in our republic. Being a girl meant you were outnumbered at physics competitions, but I never asked myself whether I should do it, I just joined in. I wanted to make my teacher proud.

It was never a question whether anyone in my family should get a college degree. Everyone knew that doors open when you get a degree. While I was interested in particle physics in high school, soon after I started at the Moscow Institute of Physics and Technology, I became interested in applied physics. I wanted to do something that would make a difference now instead of decades into the future. I had amazing advisors during my bachelor and masters projects at the Lebedev Physical Institute of the Russian Academy of Sciences who introduced me to an emerging area of quantum-well lasers, and who taught me how to manage my time.

My nanotechnology adventures started at the Technical University of Denmark where I did my PhD studies working in one of the very first Scandinavian Cleanrooms learning about nanofabrication. Focusing on how to bring light down to nanoscale, I was very fortunate to have great role models such as Ursula Keller and my university advisor, Sergey Bozhevolnyi (with whom I still collaborate very actively today).

Motivated by Doubt

I don’t think I ever felt “out of place” in the male-dominated college or research communities. For me, it was not about being female, it was about being insecure (though I admit these two things are connected). During the earlier stages of my career, I had difficulty convincing myself that I was suited for academic work. Sometimes I wanted to quit science and open a flower shop.

Once during my postdoctoral work, I felt particularly blue and seriously doubted whether I should stay in academia. In that moment, I spoke with my former PhD advisor who is a very well-known, established professor. I told him I wasn’t good enough at what I do and that I was filled with doubts. His reply surprised me: “Same here – I still have doubts about whether I am doing what I am good at.” He added that only ignorant people would ever think that they are great at something. In that moment, I realized having doubts and accepting that you don’t know everything is what motivates people to learn and explore. I am still learning to believe in myself, but the biggest reward is to share what I do know and feel passionate about.


About the Author

2018 Blavatnik National Awards Finalist, Alexandra Boltasseva, PhD, is a professor of Electrical and Computer Engineering at Purdue University working in the areas of optics and nanotechnology. She is also a mom of three and lives with her family in West Lafayette, Indiana.