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Posted June 30, 2020
Blavatnik Family Foundation
The New York Academy of Sciences
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.
Science Correspondent, BBC News
Imperial College London
University of Oxford and University College London
University of York
UK Atomic Energy Authority
University of Oxford
Imperial College London
University of Exeter
University of Southampton
University of Birmingham
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.
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.
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.”
UK Atomic Energy Authority and Culham Centre for Fusion Energy
BBC News (Moderator)
University of York
University of Oxford
University of Exeter
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.