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On March 5, 2020, the New York Academy of Sciences celebrated the Laureates and Finalists and winners of the 2020 Blavatnik Awards for Young Scientists in the United Kingdom. The one-day symposium featured fast-paced, engaging research updates from nine scientists working in diverse fields within life sciences, chemistry, and physical sciences and engineering. This year’s Blavatnik UK honorees are probing the deepest mysteries ranging from the universe to the human mind, tackling longstanding questions that have occupied scientists and philosophers for millennia. Is there life beyond our Solar system? How is knowledge organized in the brain? What is the fundamental nature of gravity? Find out how this game-changing group of young scientists is working to answer these questions in this summary of the symposium.

Symposium Highlights

• Environmental factors can influence the defense strategies bacteria use to fend off invading viruses. Insights into this process are advancing the potential for phage therapy as an alternative to antibiotics.
• New analytical and computational tools are revealing the neural machinery that allows the brain to create models of the world and facilitates decision-making and behavior.
• Chemists can exploit chirality to create novel molecules with a wide variety of applications in drug design, consumer electronics, and catalysis.
• The scientific community is closer now than ever to realizing the commercial potential of nuclear fusion as a source of clean energy.
• The first viable theory of massive gravity might help explain some of the biggest mysteries in physics, including the accelerated expansion of the universe.

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Changing the Game in Life Sciences

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Engineering Bubbles

Mechanical engineer Eleanor Stride never planned to design drug delivery systems. She was “convinced I wanted to spend my career designing Aston Martins,” until a chance discussion with a supervisor piqued her interest in therapeutic applications of engineered microbubbles. Just two microns in diameter, microbubbles can be used as ultrasound contrast agents, but Stride sees a role for these tiny tools in the fight against cancer. “In many cases, the problem with cancer drugs [is] how we deliver them,” she said, explaining that systemic chemotherapy agents often cannot penetrate far enough into tumors to be effective. These drugs can also cause side effects and damage healthy tissues.

Microbubbles can help sidestep these challenges, safely encapsulating drug molecules within a stabilizing shell.  The shell can be functionalized with magnetic nanoparticles, allowing clinicians to direct the bubbles’ aggregation at tumor sites and visualize them with ultrasound. As the bubbles compress and release in response to the ultrasound beam, the oscillation helps the bubbles penetrate into the surrounding tissue. “If we increase the ultrasound energy, we can destroy the bubble, allowing us to release the drugs on demand,” said Stride, noting that molecules released from a single 2-micron microbubble can circulate up to 100 times that diameter, pumping drugs deep into tumor tissues. This approach is highly localized—drugs are only released at the tumor site—which eliminates the potential for systemic toxic effects.

In 2019, Stride and a team of collaborators published the results of trials using oxygen-loaded magnetic microbubbles to treat malignant pancreatic tumors. In animal models, tumors treated with microbubble-delivered drugs showed dramatic spikes in cell death and also shrank in size, “which can mean the difference between a surgeon being able to remove a tumor or not,” said Stride. Additional experiments have helped hone techniques for external magnetic control of microbubbles within blood vessels to ensure precise, targeted drug delivery—a critical step toward tailoring this method for use in humans. Stride and her collaborators aim to launch a clinical trial in pancreatic cancer patients “in the very near future.”

Insights From Bacteria-Phage Interactions

As the fight against viruses dominates the news cycle, 2020 Blavatnik Awards UK Finalist Edze Westra shared an update from the front lines of a viral war billions of years in duration: the “evolutionary arms race” between bacteria and the viruses that infect them, called phages. The interactions between bacteria and phages—the most abundant biological entities on Earth—have profound implications for the development of phage-based therapies as alternatives to antibiotics.

Phages are often successful killers, but bacteria have evolved sophisticated immune strategies to resist attacks. Understanding how and when bacteria deploy each of these defensive tactics is key to designing phage therapies to treat bacterial infections.

Like humans, bacteria utilize both innate and adaptive immune responses to invading pathogens. In bacteria, innate immunity relies on the modification of surface structures to prevent phages from attaching. This system is effective, yet it creates no “record,” or memory, of which phages it encounters. The adaptive immune system, however, allows bacteria to build a database of previously encountered pathogens in the form of bits of genetic material snipped from invading phages and incorporated into the bacterium’s own DNA. The adaptive immune system, known as CRISPR immunity, forms the basis of CRISPR-Cas genome editing techniques. “There’s a critical balance between these two systems, and both are critical for survival,” said Westra, whose research aims to determine the factors that influence whether a bacterium mounts an innate or adaptive immune defense against a particular phage.

Using Pseudomonas aeruginosa, an antibiotic-resistant pathogen that often infects cystic fibrosis patients, Westra determined that a bacterium’s environment—specifically, the level of available nutrients—determined which defensive strategy was utilized. In high-nutrient environments, almost all bacteria deployed an innate immune response to phage attacks, whereas in lower nutrient settings, CRISPR immunity dominated.

In experiments using moth larvae, Westra discovered that infections were more severe when bacteria utilized CRISPR immunity, whereas bacteria that evolved innate immunity often caused less aggressive infections. “If we can manipulate how bacteria evolve resistance to phages, this could potentially revolutionize the way we approach antimicrobial resistance, with major benefits to our healthcare,” Westra said.

Building Models of the World

Computational neuroscientist Timothy Behrens is fascinated with the basic functions and decisions of everyday life—the process of navigating our home or city, the steps involved in completing household tasks, the near-subconscious inferences that inform our understanding of the relationships between people and things. Behrens designs analytical tools to understand how neuronal activity in the brain gives rise to these thought processes and behaviors, and his research is illuminating how knowledge is organized in the brain.

The activities of grid cells and place cells are well understood. By creating spatial maps of the world, grid and place cells allow us to navigate familiar spaces and locate items, such as car keys. Behrens explained that much less is known about how the brain encodes non-spatial, abstract concepts and sequence-based tasks, such as loading, running, and emptying a dishwasher. Over the past several years, Behrens and his collaborators have demonstrated that abstract information is similarly mapped as grid-like codes within the brain. “On some level, all relational structures are the same, and all are handled by the same neural machinery,” he said. This insight helps explain the effects of diseases like Alzheimer’s, which targets grid and place cells first and impacts both spatial and non-spatial knowledge.

In another line of research, Behrens is probing a phenomenon called replay, during which the brain revisits recent memories as a means to consolidate knowledge about current events and anticipate future ones. Behrens illustrated the concept by showing patterns of neuronal activity as a rat runs around a track, then rests. Even at rest, the rat’s brain displays millisecond-long flashes of neuronal activity that mimic those that take place during running. “He’s not running down the track anymore, but his brain is,” said Behrens. Replay also underlies the human ability to understand a simple story even when it’s told in the wrong order. “Our knowledge of the world tells us…what the correct order is, and replay will rapidly stitch together the events in the correct order.”

Computational tools developed in Behrens’ lab have been shared with thousands of scientists around the globe as they pursue new hypotheses about the neural computations that control cognition and behavior. “It’s an exciting time to be thinking about the brain,” Behrens said.

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Changing the Game in Chemistry

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Exploiting Molecular Shape to Develop Materials and Medicines

Consider the handshake: a greeting so automatic it takes place without thinking. Two right hands extend and naturally lock together, but as Matthew Fuchter explained, that easy connection becomes impossible if one party offers their left hand instead. The fumbling that ensues stems from a type of asymmetry called chirality. Chiral objects, such as hands, are mirror-image forms that cannot be superimposed or overlapped, and when one chiral object interacts with another, their chirality dictates the limits of their interaction. Chirality can be observed throughout nature, from the smallest biological molecules to the structures of skyscrapers.

In organic chemistry, molecular chirality can be exploited to tremendous advantage. Fuchter explained that the shape of molecules “is not only critical for their molecular properties, but also for how they interact with their environment.” By controlling subtle aspects of molecular shape, Fuchter is pioneering new strategies in drug design and devising solutions to technological problems that plague common electronic devices.

The notion of pairing complementary molecular geometries to achieve a specific effect is not unique to drug design—such synchronicities can be found throughout nature, including in the “lock and key” structure of enzymes and their substrates. Fuchter’s work aims to invent new drug molecules with geometries perfectly suited to bind to specific biological targets, including those implicated in diseases such as malaria and cancer.

Fuchter is also exploring applications for chirality in a field where the concept is less prominent—consumer electronics. Organic LED, or OLED, technology has “revolutionized the display industry,” allowing manufacturers to create ultra-thin, foldable screens for smartphones and other displays. Yet these features come at a steep efficiency cost—more than half of the light generated by OLED pixels is blocked by anti-glare filters added to the screens to minimize reflectiveness. A novel solution, in the form of chiral molecules bound to non-chiral OLED-optimized polymers, induces a chiral state of light called circularly polarized light. These circularly polarized, chiral light molecules are capable of bypassing the anti-glare filter on OLED screens. Fuchter noted that displays are far from the only technology that stands to be impacted by the introduction of chiral molecules. “Our research is generating new opportunities for chiral molecules to control electron transport and electron spin, which could lead to new approaches in data storage,” he said.

Making Use of the Mechanical Bond

Most molecules are bound by chemical bonds—strong, glue-like connections that maintain the integrity of molecules, which can be both simple, such as hydrogen, and highly complex, such as DNA. 2020 Blavatnik Awards UK Finalist Stephen Goldup’s work focuses on a less familiar bond. Mechanical bonds join molecules in a manner akin to an interconnected chain of links—the components retain movement, yet cannot separate.

Mechanically interlocked molecules have the potential to yield materials with “exciting properties,” according to Goldup, but in the decades since they were first synthesized, they have largely been regarded as “molecular curiosities.” Goldup’s lab is working to push these molecules beyond the laboratory bench by characterizing the properties of interlocked molecules and probing their potential applications in unprecedented ways. His work focuses on two types of mechanically bound molecules—catenanes, in which components are linked together like a chain, and rotaxanes, which consist of a ring component threaded through a dumbbell-shaped axle.

Goldup’s lab has taken cues from nature to introduce additional elements into rotaxanes, resulting in novel molecules with a variety of potential applications. For example, much as enzymes contain “pockets” within which small molecules can bind, rotaxanes too contain a space that can trap a molecule or ion of interest. Rotaxanes that bind metal ions have unique magnetic and electronic properties that could be used in memory storage devices or medical imaging. Inspired by proteins and enzymes that bind DNA, Goldup’s lab has also designed rotaxanes in which DNA itself is the “axle.” In theory, these molecules can be used to effectively “hide” portions of DNA and alter its biological behavior.

Perhaps most significantly, Goldup’s lab has solved a longstanding obstacle to studying rotaxanes: the difficulty of making them. The problem lies in the fact that rotaxanes can be chiral even when their components are not, making it extremely challenging to synthesize a distinct “hand,” or version, of the molecule. Recalling Matthew Fuchter’s example of how an awkward left-hand/right-hand handshake differentiates the “handedness” of two chiral objects, Goldup explained how his lab developed a technique for synthesizing distinctly “left” or “right” handed rotaxanes by utilizing a chiral axle to build the molecules. “Our insight was that by making the axle portion chiral on its own, when we thread the axle into the ring, the rotaxanes we make are no longer mirror-images of each other. They have different properties, and they can now be separated,” he said. Once separate, the chiral portion of the axle can be chemically removed and replaced with other functional groups.

Goldup’s lab is conducting experiments with new mechanically-locked molecules—including chiral rotaxane catalysts— to determine where they may outperform existing catalysts.

Amino Acids as a Portal to the Past

Scientists have multiple methods for peering into the history of Earth’s climate, including sampling marine sediment and ice cores that encapsulate environmental conditions stretching back millions of years. “But this is an incomplete picture—akin to a musical beat with no notes,” said Kirsty Penkman, the 2020 Blavatnik Awards UK Laureate in Chemistry. The records of life on land—fossil records—provide “the notes to our tune, and if we know the timing, that gives us the whole melody,” she said.  Archaeologists, paleontologists, and climate scientists can harmonize fossil records with climate history to understand the past, yet their efforts stall with fossils older than 50,000 years—the limit of radiocarbon dating.

Penkman’s lab is developing dating methods for organic remains that reach far deeper into the history of life on Earth. Their strategy relies not on the decay of carbon, but the conversion of amino acid molecules from one form to another. Continuing the theme of chirality from previous presentations, Penkman explained that amino acids exist in two mirror-image forms. However, the body only synthesizes amino acids in the “left-handed,” or L-form. This disequilibrium shifts after death, when a portion of L-amino acids begins a slow, predictable conversion to the right-handed, or D-form. The older the fossil, the greater the balance between D and L isomers. This conversion process, called racemization, was first proposed as a dating method in the 1960s. Yet, it became clear that some of the fossil amino acids were vulnerable to environmental factors that impact the racemization rate, and therefore the date.

About 15 years ago, Penkman discovered that minute stores of proteins within the remains of snail shells are entrapped in intracrystalline voids. These tiny time capsules are unaffected by environmental factors. Studies have since confirmed that shells found in older horizons, for example deeper underground, contain higher ratios of D-amino acids versus those found at younger sites, thus validating the technique.

Snail shells are often found in archeological sites, a serendipity that has led to astonishing findings about early human migration. Shells found alongside several Paleolithic tools “dated as far back as 700,000 years,” according to Penkman. “We’ve successfully shown that early humans were living in Northern Europe 200,000 years earlier than previously believed,” she said.

Penkman’s team has analyzed remains of ostrich eggshells at some of the earliest human sites in Africa, discovering fully preserved, stable sequences of proteins in shells dating back 3.8 million years. Mammalian remains are the next frontier for Penkman’s lab. They have analyzed amino acids in ancient tooth enamel—including that of a 1.7-million-year-old rhinoceros—and are developing microfluidic techniques to sample enamel from early human remains.

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Changing the Game in Physical Sciences and Engineering

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Worlds Beyond Our Solar System

For millennia, humans have wondered whether life exists beyond our planet.  Amaury Triaud, 2020 Blavatnik Awards UK Finalist believes we are closer to answering that question now than at any other time in history. The study of exoplanets—planets that orbit stars other than the Sun—offers what Triaud believes is “the best hope for finding out how often genesis happens, and under what conditions.”

The search for exoplanets has revealed remarkable variety among stars and planets in our galaxy. “The universe is far more surprising and diverse than we anticipated,” said Triaud. Astronomers have identified thousands of exoplanets since 1995, and now estimate that there are more planets in the Milky Way than stars—”something we had no idea about ten years ago,” Triaud said. Many exoplanets orbit stars so much smaller than the Sun that these stars cannot be seen with the naked eye.  Yet these comparatively small stars provide “optimal conditions” for exoplanet hunters.

Exoplanets are often detected using the transit method—as an orbiting planet passes in front of a star, its shadow temporarily dims the star’s brightness. The larger the planet relative to the star, the greater its impact on the brightness curve and the easier for astronomers to detect. While monitoring a small star 39 light-years from Earth, TRAPPIST-1, a team of astronomers, including Triaud, discovered an exoplanet system comprised of seven rocky planets similar in size to Earth, Venus, and Mercury.

“The next question is to find out whether biology is happening out there,” said Triaud, joking that the biology of interest is not little green men, but rather green algae or microbes similar to the ones that fill our atmosphere with oxygen. The presence of oxygen “acts like a beacon through space, broadcasting that here on Earth, there is life,” said Triaud, explaining that the only way to gauge the presence of life on exoplanets is through atmospheric analysis. Using transmission spectroscopy, Triaud and other astronomers will look for exoplanets that possess an atmosphere and chemical signatures of life, such as oxygen, ozone, or methane, in the atmospheric composition of exoplanets.

Such analyses will begin with the launch of the James Webb telescope in 2021.  In the meantime, a land-based mission called Speculoos, based partially in Chile’s Atacama desert, is monitoring 1,400 stars in search of additional exoplanets. “It’s rather poetic that from one of the most inhospitable places on Earth, we are on the path to investigating habitability and the presence of life in the cosmos,” Triaud said.

The Path to Delivering Fusion Power

“There’s an old joke that nuclear fusion is 30 years away and somehow always will be,” said 2020 Blavatnik Awards UK Finalist Ian Chapman, but he insists that the joke will end soon. According to Chapman, the “ultimate energy source” is entering the realm of reality. “We’re now in the delivery era, where fusion lives up to its potential,” he said. Low-carbon, low-waste, capable of producing tremendous amounts of energy from an unlimited fuel source—seawater—and far safer than nuclear fission, fusion power has a long list of desirable qualities. Chapman is the first to acknowledge that fusion is “really hard,” but his work is helping to ease the challenges and bring a future of fusion into focus.

Nuclear fusion relies on the collision of two atoms—deuterium, or “heavy” hydrogen, and tritium, an even heavier isotope of hydrogen. Inside the Sun, these atoms collide and fuse, producing the heat and energy that powers the star. Replicating that process on Earth requires enough energy to heat the fuel. of deutrium and tritium gases to temperatures ten times hotter than the Sun, a feat that Chapman admits “sounds bonkers, but we do it every day.”

Within fusion reactors called tokamaks, this superhot fuel is trapped between arrays of powerful magnets that “levitate” the jet as it spins around a central magnetic core, preventing the fuel from melting reactor walls. Yet this is an imperfect process, explained Chapman, and due to fuel instabilities, eruptions akin to “throwing a hand grenade into the bottom of the machine” happen as often as once per second. Chapman devised a method based on his numerical calculations for preventing these eruptions using additional magnet arrays that induce three-dimensional perturbations, or “lobes” at the edge of the plasma stream. Just as a propped-open lid on a pot of boiling water allows steam to escape, these lobes provide a path to release excess pressure.

Chapman’s technique has been incorporated into the “the biggest scientific experiment ever undertaken by humankind”—a massive tokamak called ITER, roughly the size of a football stadium and equipped with a central magnet strong enough to lift an aircraft carrier. Scheduled to begin producing power in 2025, ITER aims to demonstrate the commercial viability of nuclear fusion. “We can put 50 megawatts of power into the machine, and it produces 500 megawatts of power out,” said Chapman. “That’s enough to power a medium-sized city for a day.”

Even before ITER’s completion, Chapman and others are setting their sights on designing less expensive fusion devices. Late last year, the UK committed to building a compact tokamak that offers the benefits of fusion with a smaller footprint, and Chapman is the leader of this project.

The Nature of Gravity

Claudia de Rham, the 2020 Blavatnik Awards UK Laureate in Physical Sciences and Engineering, concluded the day’s research presentations with an exploration of nothing less than “the biggest mystery in physics today.”  For decades, cosmologists and physicists have grappled with discrepancies between observations about the universe—for example, its accelerated expansion— and Einstein’s general theory of relativity, which dictates that gravity should gradually slow that expansion. “The universe is behaving in unexpected ways,” said de Rham, whose efforts to resolve this question stand to profoundly impact all areas of physics.

Understanding the fundamental nature of gravity is key to understanding the origin and evolution of the universe. As de Rham explained, gravity can be detected in the form of gravitational waves, which are produced when two black holes or neutron stars rotate around each other, perturbing the fabric of spacetime and sending rippling waves outward like a stone tossed into a pond. But gravity can also be represented as a fundamental particle, the graviton, similar to the way light can be considered as a particle, the photon, or an electromagnetic wave.  Unlike the other fundamental particles such as the photon, the electron, the neutrino, or even the famously elusive Higgs boson, the graviton has never been observed. In theory, the graviton would, like all fundamental particles, exist even in a perfect vacuum, a phenomenon known as vacuum quantum fluctuation. Unknown in Einstein’s day, vacuum quantum fluctuations, when factored into the general theory of relativity, do predict an accelerated expansion of the universe. “That’s the good news,” said de Rham. “The bad news is that the predicted rate of expansion is too fast by at least 28 orders of magnitude.”

This raises the possibility that “general relativity may not be the correct description of gravity on large cosmological scales,” said de Rham. If the graviton had mass, however, it would impact the behavior of gravity on the largest scales and could explain the observed rate of expansion.

The idea of a massive graviton has been considered—and refuted—by physicists as far back as the 1930s. Several years ago, de Rham, along with collaborators Andrew Tolley and Gregory Gabadadze, “realized a loophole that had evaded the whole community.” Together, they derived the first theory of massive gravity. “Through gravity, we can now connect small vacuum fluctuations with the acceleration of the universe, linking the infinitely small with the infinitely large,” de Rham said.

Determining the mass of the graviton requires the most precise scale imaginable, and de Rham believes that gravitational wave observatories are perfectly suited to the task. Whether her theory will hold up in future tests remains to be seen, but when it comes to solving this epic mystery, “the possibility is now open.”

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Panel Discussion: Hopes for the Future

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Several Laureates and Finalists of the 2020 Blavatnik Awards in the UK joined BBC science reporter Victoria Gill for the final session of the day, a wide-ranging panel discussion that touched on issues both current and future-looking.

Two themes—fear and opportunity— emerged as powerful forces shaping science and society, especially as it relates to climate change and the threat of emerging infectious disease. Gill noted that climate change is “the biggest challenge ever to face humanity,” and that many efforts to raise awareness of its impacts focus on bleak projections for the future. Asked for insights on shifting the tone of climate change communications, Kirsty Penkman acknowledged that “there needs to be a certain level of fear to get people’s attention.” She then advocated for a solutions-oriented plan rooted in the fast pace of scientific progress in clean energy, among other areas. “This is an amazing opportunity,” she said. “Humans are ingenious….in the last 120 years we’ve moved from a horse-drawn economy to a carbon-based economy, and in 5 or 20 years we could be in a fusion-based economy. We have the potential to open up a whole new world.” Eleanor Stride suggested combatting complacency by emphasizing the power of small changes in mitigating the impact of climate change. “One billion people making a tiny change has a huge impact,” she said.

The specter of a coronavirus pandemic had not yet become a reality at the time of the symposium. But Edze Westra presciently detailed the challenges of containing a highly contagious emerging pathogen in a “tightly connected world.” He commented that detecting and containing emerging diseases hinges on the development of new diagnostics, and that preventing future outbreaks will require cultural shifts to limit high-risk interactions with wildlife. For zoonotic diseases such as the novel coronavirus, “it’s all about opportunity,” Westra said.

Panelists also looked to the future of science, touching on issues of equality, discrimination, and diversity, and emphasizing the importance of raising the bar for science education. Stride noted that children are natural scientists, gravitating toward problem-solving and puzzles regardless of nationality or gender. “But something happens later,” she said, lamenting the drop in interest in science as children progress in school. “One of the things that gets lost is that creativity, which is what science really is—we’re coming up with a guess and trying to gather evidence for it—we’re not just learning a huge number of facts and regurgitating them,” she said.

In the wake of Brexit, panelists expressed concern about potential difficulties in attracting international students to their labs. “Diversity is so important,” said Penkman. “Getting ideas from all around the world from people with different backgrounds is essential to making science in the UK—and the world—the best it can be.” In her closing comments, Penkman said that ultimately, the trajectory of science comes down to the people in the field. “My eternal optimism is in the people I work with and the people I talk to when I visit schools—it’s that innate interest and curiosity. Whenever I see it, I feel that is the future of science,” she said.

Overview

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

Symposium Highlights

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

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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.

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.

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.

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

Further Readings

Quantum Optics

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Highlights

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

Atomic Clocks: From Timekeepers to Quantum Computers

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

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

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

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

Further Readings

Chemical Biology

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Highlights

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

Gut Reactions: Understanding the Chemistry of the Human Gut Microbiome

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

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

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

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

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

Further Readings

Synthetic Methodology

Speakers

Highlights

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

Boron Nitride: A Surprising Catalyst

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

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

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

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

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.

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

Advances in Neuroscience

Speakers

Highlights

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

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 Na_v 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.

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 Na_v 1.7, but also characterized small molecules—mostly derived from animal toxins—that precisely and selectively interfere with its function. Developing synthetic drugs based on these molecules is the next phase of discovery, and it’s one that may happen more quickly than expected. “When I started my lab, I thought resolving this protein’s structure would be a lifetime project, but we shortened it to just five years,” said Yan.

Further Readings

Computer Science

Speakers

Highlights

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

Machine Learning with Networks

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

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

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

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 21^st 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.

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

Further Readings

Materials Science

Speakers

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.

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.

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

Further Readings

Medicine and Medical Diagnostics

Speakers

Highlights

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

Single Cell Genomics: A Revolution in Cancer Biology

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

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

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

Single-cell 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.

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

Further Readings