Turning data into predictive models is not a simple task.
Published April 14, 2020
By Roger Torda
Shelf life is an important variable when it comes to snack foods. But how can shelf life be predicted when new products are being developed?
The starting point is often data from taste tests. Turning that data into a predictive model is not a simple task. And that is why PepsiCo, teaming with The New York Academy of Sciences, posed the problem as a challenge to young scientists.
Pallavi Gupta, who is pursuing her PhD in Informatics at the University of Missouri, Columbia, was the Grand Prize winner in the Data Science in Research & Development Challenge. And as a result she will head to Valhalla, New York in the Summer of 2020, for an internship with PepsiCo’s R&D Data Analytics team.
“I love to analyze data,” Pallavi said, quickly breaking into laughter. “I am looking forward to the internship with PepsiCo, to test my skills and to gain additional experience with data analytics using machine learning techniques.”
Competing Against Hundreds of Innovators
Pallavi was among 1,235 registrants in the Challenge. Jhansi Kurma, who recently earned a master’s degree in Business Information Systems from the New Jersey Institute of Technology, came in second.
PepsiCo turned to the Academy to host the competition because of its experience running innovation challenges in science and technology, dating back to 2010. Many of the Academy’s challenges target early career scientists. Other Academy challenges are for high school students.
“The New York Academy of Science-led data challenge has proven to be an excellent way to reach talented data scientists from around the world and have them work on real life challenges together with PepsiCo’s experts. We are looking forward to the 2020 edition and are committed to make this an annual tradition,” says Ellen de Brabander, PepsiCo’s Senior Vice President for Research and Development, said the Data Science Challenge.
The Value of STEM Skills
Large, diverse companies like PepsiCo, value STEM skills across a wide range of job functions.
“In global research and development, our number one output is innovation, and STEM [skills] are critically important competencies to drive innovation,” the company’s James Yuan said in a NYAS webinar titled “Why STEM Professionals are Valuable Across Industries.”
Yuan, Pepsico’s Senior Director, Data Science & Analytics, went on to explain that students joining R&D at the company can pursue work in a wide variety of areas, including product formulation, packaging, process engineering, food safety, quality control, and regulatory affairs.
“In e-commerce and in global business, there are also a lot of opportunities to leverage STEM capabilities for business optimization,” said Eric Higgins, PepsiCo VP, Data Science and Analytics. “We’re talking about media buys, we’re talking about identifying how to best place our products, product assortment, and supply chain optimization.”
A lot of product innovation within this company comes through simply hypothesis testing,” Higgins continued. “Using data science and STEM disciplines, we’re able to automate that process and expand capability, so we can find new ways of innovating. So, in both R&D and on the business side, there are opportunities across the board for people using new methodologies in mathematics, statistics, and computer science.”
Developing a Useful Shelf-Life Model
Competitors in the Challenge were each given a data set from 81 individual shelf-life studies. The data came from evaluations of changes in the taste of snack products as they aged. The goal was to develop a useful shelf-life model that would allow a product developer to predict shelf life based on the product, process, packaging information, and storage conditions related to where the product would be sold.
The competitors had 14 days to complete the challenge. Ten finalists then presented their solutions virtually to a panel of judges, made up of PepsiCo employees from Data Science, R&D, and Human Resources departments.
Pallavi is working toward her PhD, and is using computational and machine learning approaches to study how small non-coding RNA (also known as “small RNAs) – are involved in gene expression regulation. Pallavi said she would take skills from her upcoming internship and apply them to her own research in genomics.
The Data Science in Research and Development Challenge drew entries from 42 countries, especially from the US, Ireland, the UK, Canada and India.
Mammalian cells can make up to 20,000 different proteins, which are responsible for a wide range of cellular functions, including structure, catalysis, transport, and signaling. Proteins are synthesized as linear chains, but to carry out their myriad roles, they must then fold into complex three-dimensional configurations.
Franz-Ulrich Hartl, MD, of the Max Planck Institute of Biochemistry and Arthur Horwich, MD, of Yale School of Medicine and Howard Hughes Medical Institute, have dedicated their careers to better understanding the molecular machinery that drives protein folding, and the implications when a protein misfolds. In doing so, they discovered a new class of proteins, part of the chaperone family, responsible for protein folding.
Chaperones bind to peptide chains as they are being transcribed to prevent them from aggregating and to give them an isolated, quiet space, shielded from the hubbub of the crowded cytoplasm, in which to fold properly. This process is essential to human biology and health, because misfolded proteins are associated with aging and diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and prion disease.
On October 4, 2019, prominent scientists gathered at the New York Academy of Sciences to grant the 2019 Dr. Paul Janssen Award to Hartl and Horwich for their groundbreaking insights into chaperone-mediated protein folding. The symposium included award lectures from the honorees, as well as presentations on several aspects of protein folding, from basic biology to the implications for human disease.
Symposium Highlights
While studying mitochondrial protein import, Horwich and Hartl hypothesized that the process may not be spontaneous but dependent on cellular machinery. They discovered a new class of proteins responsible for protein folding.
Hsp60, its bacterial homolog GroEL, and its eukaryotic homolog TRiC have a double ring structure that forms a chamber in which a peptide substrate can fold into its proper shape.
The unfolded protein response of the endoplasmic reticulum responds to the presence of misfolded proteins, which accrue with age. The response itself declines with age.
Hsp70 is a diverse family of monomeric chaperones that binds to polypeptide chains as they’re being translated or when they misfold from mutation or stress and prevents them from collapsing into aggregates.
Clinically relevant receptors that have been difficult to treat require specific chaperones that may provide more easily druggable targets for neurological and psychiatric disorders.
Honorees
Franz-Ulrich Hartl, MD Max Planck Institute of Biochemistry
Arthur Horwich, MD Yale School of Medicine and Howard Hughes Medical Institute
Speakers
David S. Bredt, MD, PhD Janssen Pharmaceutical Companies of Johnson & Johnson
Andrew Dillin, PhD University of California, Berkeley and Howard Hughes Medical Institute
Judith Frydman, PhD Stanford University
Lila M. Gierasch, PhD University of Massachusetts Amherst
Event Sponsors
This symposium was made possible with support from:
Dr. Paul Janssen Award Lectures
Speakers
Franz-Ulrich Hartl Max Planck Institute of Biochemistry
Arthur Horwich Yale School of Medicine and Howard Hughes Medical Institute
Highlights
Chaperones prevent the formation of toxic protein aggregates, and failure of the chaperone system is associated with numerous age-dependent proteopathies and neurodegenerative diseases.
GroEL mediates two key actions on a substrate polypeptide: binding in the open ring forestalls aggregation and can exert unfolding, while binding in the closed ring holds the polypeptide in “solitary confinement,” giving it a chance to fold on its own and alleviating the risk of aggregation.
Molecular Chaperones — Central Players of the Proteostasis Network
“Protein folding is the final step in the information transfer from gene to functional protein, and as such is of fundamental biological importance,” began Franz-Ulrich Hartl.
In the 1950s, biochemist Christian Anfinsen showed that denatured proteins could refold spontaneously in vitro, thus revealing that all of the information required for a protein to attain its final structure is contained in its amino acid sequence. The study was somewhat misleading, however, as it only used small proteins — under 100 amino acids long — and it started with a completely synthesized amino acid chain. This hardly recapitulates the conditions under which proteins must fold in the cell, where many proteins are large, have multiple domains, fold as they are being synthesized on the ribosome, and are in the very crowded cytoplasm.
In the late 1980s, growing evidence showed that cellular machines were required to help proteins fold “at biologically relevant timescales.” These machines were deemed molecular chaperones, as they help proteins achieve their final active conformations but are not themselves part of the final structure. Hartl and Horwich initially discovered chaperones using mitochondria as a model system.
Mitochondria import about 1,000 proteins from the cytoplasm, and these proteins must be unfolded to get across the mitochondrial membranes. Based on Anfinsen’s experiments, it was thought that they would then spontaneously fold properly once inside the mitochondria. But proteins in yeast with mutant Hsp60 got into the mitochondria but failed to fold, identifying Hsp60 as a required chaperone.
Chaperones like Hsp60 prevent the formation of protein aggregates. Aggregation can occur in the intermediate stages of multidomain protein folding when hydrophobic regions might become exposed; chaperones protect these hydrophobic regions through multiple rounds of binding and releasing the partially folded proteins.
ATP binding and hydrolysis often mediate these bind-and-release cycles. The chaperones provide a safe space for the proteins to fold, sequestered away from the hubbub of the cytoplasm. Proteins revisit the quiet chambers that chaperones provide throughout their lifetimes, not only as they are being synthesized.
In the current model, while an amino acid chain is being translated, it interacts with a nascent-chain-binding protein like Hsp70, a type of chaperone that binds to hydrophobic peptide segments. Hsp70 prevents premature misfolding, only allowing the protein to fold when enough structural information for productive folding becomes available — when the protein chain gets long enough.
Most proteins only require this type of chaperone to fold efficiently. But some have more complicated structures and need to fold in the isolated, constrained cage of a cylindrical chaperonin complex like Hsp60, the chaperone that Hartl and Horwich first isolated from mitochondria. Bacterial GroEL and its cofactor GroES are the most well-studied of this class of chaperones; the eukaryotic cytoplasmic versions are called TRiC or CCT.
Chaperones are only one facet of cellular regulation of proteostasis, or protein quality control. They prevent proteins from misfolding, and the degradation machinery eliminates proteins that do not misfold.
There is an age-dependent decline in chaperone function, though. Since chaperones are required for protein maintenance, this decline can lead to a buildup of protein aggregates — which then further strains the already declining chaperones.
These protein aggregates lead to neurodegenerative diseases like Alzheimer’s disease and Huntington’s disease. Aggregates of different disease proteins have the same amyloid fibrillar structure, which suggests that a basic pathological mechanism may underlie all of these diseases. Hartl found that the aggregates interfere with almost every aspect of cellular machinery — transcription, translation, nuclear translocation, DNA maintenance, protein degradation, cytoskeletal organization, and vesicle transport —not only chaperones. But as they overwhelm the chaperone system, toxic aggregates build up until they cause cell death.
Thus, he suggests that rebalancing the proteostasis network may be a means of treating these neurodegenerative diseases.
Chaperonin-mediated Protein Folding
Arthur Horwich described how, in a classic bedside-to-bench approach, he discovered that chaperonin ring machines function to mediate protein folding. He studied the lethal X linked inherited metabolic disease caused by the mutant mitochondrial enzyme OTC. OTC is the second step in the urea cycle; when it is defective, cells can’t clear urea.
Since it is X linked, baby boys with nonfunctional OTC die. Horwich isolated the OTC cDNA and found its mitochondrial transport signal, then looked for a yeast mutant that could transport unfolded human OTC into the mitochondria but in which the transported OTC would not then fold. The yeast mutant he found lacked Hsp60.
Mitochondrial Hsp60, and its bacterial counterpart GroEL, performs two vital functions: they bind to polypeptides to prevent the formation of protein aggregates, and they help polypeptides achieve their functional state. In 1994 and 1997, the X-ray structures of both GroEL alone and in complex with its cochaperonin single ring GroES were presented along with structure-function studies in collaborative work with the late Paul Sigler, providing insight into how the machinery works.
The Binding of GroES to one end of the GroEL cylinder widely expands the folding chamber, giving the substrate space to fold in isolation from the busy cytosolic environment.
GroEL is a cylinder made of 14 identical subunits arranged into two back-to-back 7-membered rings. Each of the subunits is folded into: an equatorial domain, at the waistline of the cylinder, the collective of which hold the assembly together via side-by-side contacts within a ring and contacts of subunits between the two rings; a hinge like “intermediate” domain interconnecting the equatorial and apical domain; and a terminal “apical” domain at an end of the cylinder.
The equatorial domains each house an ATP binding pocket at the inside aspect and the cooperative binding of 7 ATP’s in a GroEL ring causes the terminal GroEL apical domains, attached to the equatorial domains through the slender intermediate domains, to open up like flower petals. In their “unopened” position the apical domains surround an open central cavity of 45 Angstrom diameter and each apical domain proffers sticky “hydrophobic” surface at its cavity-facing aspect.
The continuous hydrophobic surface around the ring specifically captures an unfolded protein species via its own exposed hydrophobic surface (that will become buried to the interior in the final folded “native” form). Thus the binding of a non-native protein by an open GroEL ring serves to capture the protein’s sticky hydrophobic surfaces, masking them, and preventing them from interacting with other unfolded proteins which can lead to aggregation.
When a polypeptide-bound ring of GroEL binds the cochaperonin ring, GroES, a smaller 7-membered single ring of identical subunits, in the presence of ATP, now a large movement of the apical domains occurs, both clockwise rotation and further elevation (see Figure; GroES is colored gold and the GroEL ring undergoing large movements is green). The large movements remove the hydrophobic polypeptide binding surface from facing the cavity, and the lining of the now GroES-encapsulated GroEL cavity becomes watery (hydrophilic) in character.
The large twisting apical domain movements strip the polypeptide off of the cavity wall into the now encapsulated and watery (hydrophilic) cavity where the protein folds in “solitary confinement,” as Horwich phrased it, without any chance of aggregation. Subsequently, after this longest step of the reaction cycle (~10 sec), ATP hydrolyzes, GroES releases, and out from the cavity comes the polypeptide whether properly folded or not. If it has not reached native form, it can make another try at proper folding, either by entering another GroEL cavity, or becoming bound to a different chaperone.
Andrew Dillin University of California, Berkeley and Howard Hughes Medical Institute
Highlights
There are a considerable variety of chaperones that are structurally and functionally different from recognizing and binding nonnative proteins in all of their various stages and processes.
The endoplasmic reticulum unfolded protein response evolved to protect the organism from infection. In the nervous system, it can act in a non-autonomous manner to promote transcription in response to stress.
The TRiCKy Business of Folding Proteins in the Cell
“Proteins are astoundingly complex,” said Judith Frydman. As an example, she pointed to the mammalian respiratory complex I, the 45-subunit complex that drives protons across the inner mitochondrial membrane. Thus, the potential problems with protein folding are not limited to the folding process.
Chaperones bind unfolded polypeptides to help them achieve their native state. Still, much more than that, they engage polypeptides at every stage of their existence in the cell, waiting to receive them as they’re translated and monitoring for damage throughout their lifespans.
TRiC, or CCT, is the stacked chaperone in eukaryotic cells — the equivalent of GroEL. However, unlike GroEL, it does not have a separate cap. It requires ATP hydrolysis, which closes the lid to allow folding; but ATP binding is not sufficient. TRiC binds nascent chains when they are almost complete, while they are still on the ribosome but after they have interacted with Hsp70.
The complex only binds precise types of folding intermediates — notably those with complex topologies like p53, tubulin, actin, telomerase, F box proteins, and others — and then comes off once that folding intermediate has resolved into its properly folded domain. It also suppresses amyloid aggregation, but is overexpressed in many cancers and has been linked to poor prognosis in lung and breast cancer.
Subunit diversity confers unique molecular features to TRiC-mediated folding.
TRiC descends from the chaperone in archaea, which only has one type of subunit. The heteromeric nature of eukaryotic TRiC allows it to form an asymmetrical complex. TRiC has eight subunits, and each subunit has a different affinity for ATP; these subunits are arranged with high-affinity subunits around one side of the ring and low-affinity subunits around the other side.
The subunits have varying degrees of affinity for substrates as well, with each subunit’s binding site presenting a distinct and evolutionarily conserved surface of polar and hydrophobic residues. Their combination thus broadens TRiC’s binding specificity.
Once the binding chamber is closed, one hemisphere is positively charged and the other is negatively charged, further orienting how the substrate can bind and influencing its folding trajectory. Frydman called it a “chaperone with an opinion,” rather than a cage, “that guides the substrate where it needs to go.”
Prefoldin is a cofactor for TRiC, so named because it was thought to facilitate substrate transfer to TRiC before the substrate folded. It binds to TRiC in TRiC’s open state, and, like TRiC, it has a charge asymmetry and a specific pattern of polar and hydrophobic residues that contribute to the inner surface of TRiC’s binding chamber. Prefoldin seems to enhance both the yield and the rate of folding. In vivo, it must bind to TRiC, or else massive protein aggregation builds up in the cell.
Perceiving ER Stress
As many as thirteen million proteins fold and mature in the endoplasmic reticulum (ER) every minute. It is no wonder then that defects in ER function are strongly associated with metabolic and age-related disorders. The unfolded protein response in the ER (UPRER) responds to the presence of unfolded proteins by inducing the transcription of chaperones, and it declines with age. Andrew Dillin wondered how this UPRER works in multicellular organisms.
Are unfolded proteins detected in each individual cell by its own machinery, in a stochastic manner? Or might there be a higher order of regulation, coordinating protein folding mechanisms across the whole system? He turned to C. elegans to figure it out. Since all of the cells in the adult C. elegans are post mitotic, the worm provides a great model system for studying proteome maintenance.
The Dillin lab demonstrated that the neuronal transcription factor XBP-1 could rescue the age-dependent decline in ER proteostasis. Overexpression of XBP-1 extends the worm’s life. XBP-1 — which has the very unusual property that its mRNA is spliced in the cytoplasm instead of the nucleus — senses unfolded proteins and induces the UPRER in nerve cells. These nerves then send signals to peripheral and distal cells, causing them to activate their own UPRER.
Only neuronal cells, both neurons and glia, respond to XBP by inducing the UPR. The peripheral cells don’t sense the unfolded proteins and respond to them; they respond to the signal from the brain. Neurons require small, clear vesicles to send this signal, indicating that neurotransmitters are involved. Unlike neurons, glia need dense core vesicles, suggesting that they signal through neuropeptides or biologic amines rather than neurotransmitters. The neuronal and glial effects are synergistic, and the mechanism is conserved in mice.
XBP-1 induces the UPR from both neurons and glia, but uses different pathways to signal from the different cell types.
The UPRER “only deals with the challenge after the damage has occurred” said Dillin. Wouldn’t a protective system be preferable?
Thus, he conducted a CRISPR screen to find such a system, of UPRER regulators that would identify and protect the organism from ER stress instead of just responding after it happens. In doing so, Dillin found TMEM2, a transmembrane hyaluronidase that had not been previously implicated in ER stress. It does not activate the UPRER, which can induce apoptosis. Rather, it acts through the MAP kinase pathway to promote stress resistance in the ER and survival of the organism.
By breaking down extracellular hyaluronan, it generates a smaller product that increases ER stress resistance. TMEM2 is conserved from worms all the way through humans; it senses the stress from outside the plasma membrane of brain cells, before the stress hits, and then sends the signal to the periphery. Dillin does not yet know how TMEM protects the ER from stress, but he knows that it is not through chaperones.
Franz-Ulrich Hartl Max Planck Institute of Biochemistry
Arthur Horwich Yale School of Medicine and Howard Hughes Medical Institute
Lila M. Gierasch University of Massachusetts Amherst
David S. Bredt Janssen Pharmaceutical Companies of Johnson & Johnson
Seema Kumar (Moderator) Johnson & Johnson
Highlights
The Hsp70 allosteric cycle involves major conformational changes, alternating between a docked state with bound ATP and low affinity for unfolded protein substrates and an undocked state in which the α-helical lid rotates out of the way to allow substrate binding and ATP hydrolysis.
Receptors implicated in neuronal and psychiatric disorders often require specific chaperones to help them fold; these chaperones are often expressed only in specific areas of the brain, and thus may provide appropriate drug targets.
The Versatile Hsp70 Molecular Chaperones Machine
Lila Gierasch introduced Hsp70 as the “early greeting committee” for nascent polypeptide chains. It can maintain the chains in an unfolded state for transport across membranes and meet them on the other side. Hsp70 can also give them a second chance to fold if things don’t go right the first time around. Like all chaperones, it prevents aggregation. It acts as a monomer, but that hardly makes it simple.
Hsp70 activities depend on intramolecular allostery controlled by ligand modulation of an energy landscape. The C-terminal substrate-binding domain (SBD) binds to short hydrophobic stretches of a polypeptide chain. ATP binding to the N-terminal nucleotide-binding domain (NBD) reorients the NBD actin fold. It decreases the affinity of the SBD for the substrate, and the substrate activates the NBD ATPase activity. The α-helical lid can rotate, allowing access to either the SBD or the NBD.
Hsp70 shifts between a docked, ATP bound state with low substrate affinity and an undocked, ADP bound state with high substrate affinity.
Hsp70 allosteric landscapes can be shaped by the strength of interdomain interfaces and as well as ligand binding, making them “tunable molecular machines.” They must have promiscuous selectivity because they bind an immense number of substrates with varying affinities.
There are Hsp70 molecules bound approximately every 40 amino acids throughout the proteome, and there is evidence that more than one Hsp70 molecule can bind to one substrate, mainly to keep it unfolded as it is translocated. And there are many isoforms of eukaryotic Hsp70 with different allosteries. These could have evolved through interactions with co-chaperones, post-translational modifications like phosphorylation, and even the sequence of the substrate.
Gierasch suggested that tweaking its allostery might modulate Hsp70 activity, or one class of Hsp70 could be targeted over another to treat particular diseases. It is tempting to think of activating the chaperone network to prevent neurodegeneration, but it is risky, too, since cancer cells often rely on mutant chaperones.
Getting a Handle on Neuropharmacology by Targeting Receptor Chaperones
Abnormalities in psychiatric diseases are heterogeneous across brain regions, with increased activity in some areas and decreased activity in others. It has been very difficult to find small molecules that can affect synaptic transmission in these different regions.
Stargazer mutant mice, that constantly look up because they have epilepsy, don’t have functional AMPARs (a type of glutamate receptor) on their cerebellar granule cells. David Brendt found that the receptors didn’t work because the mice lacked a chaperone he named stargazin. Stargazin is a Transmembrane AMPAR Regulatory Protein, or TARP, a family of proteins that Bredt said, “act more like escorts than chaperones.”
TARPs take the AMPARs from the endoplasmic reticulum to the cell surface at the synapse of cerebellar granule cells. Different TARPs are distributed to different brain regions, making them attractive drug targets. A molecule that disrupts the interaction between TARP-γ8 and AMPAR has been shown to inhibit neurotransmission in the hippocampus.
Thus, TARPs could be key to treating epilepsy without the terrible side effects of current anticonvulsants, and could possibly be used to treat bipolar disorder, schizophrenia, and anxiety.
Clinically relevant receptors that have been difficult to treat pharmacologically, like AMPAR and nAChRs, have specific required chaperones — TARPS and NACHO, in this case — that may provide more easily druggable targets.
Acetylcholine receptors are the site of action for a number of Alzheimer’s drugs that induce modest but reproducible improvements in cognition. These pentameric receptors have been very difficult to study in the lab, though, because they only fold properly in neuronal cells.
Bredt recognized this as an opportunity in addition to a challenge. His lab cotransfected a library of 4,000 transmembrane proteins along with the acetylcholine receptor into HEK cells and screened for any that would help the receptors fold. Only one did, a novel transmembrane protein with no homology to anything, found in one copy in mammals and Drosophila and not found in worms or yeast at all. They named it NACHO. It resides in the membrane of the endoplasmic reticulum in neuronal cells, and it mediates the folding of nicotinic acetylcholine receptors.
Panel Discussion
Highlights
We don’t know why protein aggregates are toxic, or why chaperones’ ability to prevent their formation wanes with age.
Future research should focus on understanding the proteostasis network in a physiological context and figuring out if, and how, it is an appropriate clinical target.
The day ended with a panel discussion in which Hartl and Horwich fielded questions. Many of them focused on the role misfolded proteins play in disease, why they accumulate with age, and if, when, and how the proteostasis machinery can be targeted therapeutically.
Moderator Seema Kumar began the panel by asking about the greatest challenges and limitations in the field. Horwich replied that we don’t understand the toxicity of misfolded proteins; we don’t even know if they themselves are toxic, or if they are recruiting other toxic mediators. He speculated that it would be great if we could monitor single polypeptide chains as they fold, to see which ones go astray and how that makes them toxic.
Since antibodies against amyloid plaques have been ineffective in Alzheimer’s disease, enhancing multiple parts of the proteostasis network might be a better strategy than targeting specific misfolded proteins or chaperones. Horwich also pointed out that we don’t know why aging thwarts chaperones: does their ability to handle their task decline, or are there genomic or proteomic issues? Hartl added that we don’t understand neurodegenerative diseases nearly well enough to know the role that protein folding plays in their development; Parkinson’s disease, for instance, is likely more than one monolithic disease.
As for how the field will unfold in the future, Horwich noted that most of what we know about protein folding mechanisms comes from in vitro studies with purified components. So we need to know more about how the cellular milieu affects binding affinities and folding. It would be helpful to determine how many times a particular ligand comes back to a particular chaperone. Hartl explained the importance of figuring out who the first responders are, who the next responders are, and if we can develop small molecules to affect the proteostasis machinery.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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 2019 honorees of the Blavatnik Awards for Young Scientists in the UK2019 Blavatnik Awards Laureate Professor Konstantinos Nikolopoulos Professor of Physics at the University of BirminghamBack Row (Left to right) The 2019 Finalists: Kathy Niakan, Igor Larrosa, Rachel O’Reilly, Gustav Holzegel, Máire O’Neill, Timothy Behrens; Front Row (Left to right) The 2019 Laureates: Philipp Kukura, Ewa Paluch and Konstantinos Nikolopoulos2019 Blavatnik Awards Laureate in Chemistry, Prof. Philipp Kukura, University of Oxford2019 Blavatnik Awards Laureate in Life Sciences, Prof. Ewa Paluch of UCL and University of Cambridge with Sir Leonard Blavatnik
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.
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.
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.
“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.
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.
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.
