Three outstanding Israeli Scientists win the 2018 Blavatnik Awards for Young Scientists in Israel during its inaugural year.
Published May 1, 2018
By Kamala Murthy
For over a decade in the United States, the Blavatnik Awards have honored exceptional young scientists and engineers. The award highlights their extraordinary achievements, recognizing their remarkable promise for future discoveries, and accelerating innovation in their research.
Established in 2007, the Blavatnik Awards are a signature program of the Blavatnik Family Foundation that are administered by the New York Academy of Sciences. Awarded in Israel for the first time – in collaboration with the Israel Academy of Sciences and Humanities – three of the country’s most outstanding young scientists and engineers will receive $100,000 each, one of the largest unrestricted prizes ever created for early-career researchers in Israel.
From 47 nominees, encompassing Israel’s most promising scientific researchers aged 42 years and younger and nominated by Israeli research universities, a distinguished national jury selected three outstanding laureates, one each from the disciplines of Life Sciences, Chemistry, and Physical Sciences & Engineering:
Dr. Oded Rechavi Senior Lecturer, Department of Neurobiology, Tel Aviv University
Dr. Charles Diesendruck Assistant Professor of Chemistry, Schulich Faculty of Chemistry, Technion – Israel Institute of Technology
Prof. Anat Levin Associate Professor, The Andrew & Erna Viterbi Faculty of Electrical Engineering, Technion – Israel Institute of Technology
The inaugural Blavatnik Awards for Young Scientists in Israel will be honored at a formal ceremony in Jerusalem on February 4, 2018. The Laureates will join a network of their peers as members of the Blavatnik Science Scholars community. The net work is currently comprised of over 220 Blavatnik Award honorees from the decade-old U.S. program. Laureates will also be invited to attend the annual Blavatnik Science Symposium at the Academy each summer. Here the Scholars come together to exchange new ideas and build cross-disciplinary research collaborations.
To learn more about this year’s Blavatnik Laureates and other honorees, please visit the Blavatnik website here and follow us on Twitter: @BlavatnikAwards.
The Innovators in Science Award Honorees are Breaking New Ground in Neuroscience: Dr. Kay Tye has made discoveries between neural networks and social interaction.
Published May 1, 2018
By Anni Griswold
Albert Einstein reportedly once said, “Not everything that can be counted counts, and not everything that counts can be counted.” Though the 2017 honorees of the Innovators in Science Award have plenty of countable achievements, their stories reveal a common thread — creative approaches to their work and the development of disruptive tools that transformed scientific understanding in their discipline.
Bridging Psychology and Neuroscience
As an undergraduate at the Massachusetts Institute of Technology, Kay Tye, PhD, an Early-Career Scientist Finalist, enjoyed taking psychology classes alongside her load of neuroscience coursework. But the contrast revealed each field’s shortcomings. Psychology felt unsatisfying, she says, because it lacked a mechanism to trace thought and emotion back to neural mechanisms. And neuroscience focused on sensory or motor systems without hinting at how these systems give way to thought and emotion.
Eventually, she devised a plan to bridge the fields. She began using optogenetics to tease apart the underpinnings of motivation and reward. “The dream has always been to completely understand on every level how complex social and emotional representations exist in the brain,” says Tye, Assistant Professor at MIT’s Picower Institute for Learning and Memory. Using this approach, Tye has made startling discoveries about the neural networks involved in social interaction, including the finding that loneliness drives social interaction.
Going forward, she aims to explore how social representations are parsed in the brain. This research program, she says, could someday lead to targeted therapeutics for psychiatric conditions that have minimal side effects.
“If we understand the cells and circuits and synapses that give rise to different emotional states,” she says, “then we can understand when there are perturbations and how to fix them.”
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The Innovators in Science Award Honorees are Breaking New Ground in Neuroscience: Dr. Michael Halassa’s research on AI systems could impact our perception of reality.
Published May 1, 2018
By Anni Griswold
Albert Einstein reportedly once said, “Not everything that can be counted counts, and not everything that counts can be counted.” Though the 2017 honorees of the Innovators in Science Award have plenty of countable achievements, their stories reveal a common thread — creative approaches to their work and the development of disruptive tools that transformed scientific understanding in their discipline.
Biological Underpinnings of the Mind
Michael Halassa
Michael Halassa, MD, PhD, an Early-Career Scientist Finalist, has traced the neural correlates of cognition from the thalamus to the cortex and beyond. But his interests in neurocomputational frameworks trace back even farther — to the first time he watched “The Matrix.”
As he watched the film’s characters grapple with a simulated reality, Halassa began wondering how something as intangible as the mind can perceive reality in the first place. If we were to look inside the brain, he wondered, where would we find the mind? How do we make decisions and solve problems?
“If we can understand how these functions are normally accomplished by the physical device we call the brain, then we’ll have a better understanding of how these functions go awry in conditions such as schizophrenia, autism or ADHD,” says Halassa, an Assistant Professor of Brain and Cognitive Science at Massachusetts Institute of Technology (nominated while at New York University in New York).
Computational Frameworks
Halassa abandoned the traditional tactic of studying the molecular and electrical properties of individual cells. Instead, he assembled computational frameworks that could map physical features, such as synapses, onto abstract processes such as thought. His approach revealed that the thalamus, a brain region long assumed to relay simple sensory input to the cortex, actually streams detailed instructions that allow the cortex to shift between tasks.
“From moment to moment, your brain reconfigures on the fly to perform different types of tasks. That reconfiguration is what defines things like intelligence, productivity and performance.” Glitches in this network configuration may contribute to psychiatric diseases, he says.
His findings could lead to artificial intelligence systems that display similar cognitive flexibility. Such “neuromorphic computing” could lead to a greater understanding of how we perceive reality.
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The Innovators in Science Award Honorees are Breaking New Ground in Neuroscience: Dr. Viviana Gradinaru’s research enables scientists to visualize neuron and cell behavior.
Published May 1, 2018
By Anni Griswold
Albert Einstein reportedly once said, “Not everything that can be counted counts, and not everything that counts can be counted.” Though the 2017 honorees of the Innovators in Science Award have plenty of countable achievements, their stories reveal a common thread — creative approaches to their work and the development of disruptive tools that transformed scientific understanding in their discipline.
Illuminating the Brain’s Circuitry
Viviana Gradinaru
As an undergraduate, Viviana Gradinaru, PhD, the Early-Career Scientist Winner, became fascinated with the underpinnings of neurodegeneration. But few tools existed to dissect the phenomenon. Undeterred, she set out to create her own.
During graduate school, Gradinaru borrowed light-sensitive proteins from algae and bacteria and introduced them to mammalian neurons. Her hope was to switch individual cells on or off in response to laser stimulation. Using this strategy, she revealed how specific brain circuits underlie locomotion, reward and sleep. One of Gradinaru’s tools, dubbed “eNpHR3.0,” is now widely used in the field of optogenetics — a field that her work helped launch.
Now an Assistant Professor of Biology and Biological Engineering at Cal Tech, Gradinaru has moved on to other tools and methods. This includes tissue-clearing techniques that render organs transparent. These see-through systems allow scientists to visualize where neurons start and stop. They also study how the cells behave along the way.
Gradinaru’s team was also among the first to introduce vectors that can shuttle genes across the blood-brain barrier with high efficiency. These genes can express colors. This allows scientists to visualize neural pathways, or they can normalize biochemical or electrical properties in a disease model.
“Developing tools and perfecting them to the level where they can work in other people’s hands,” she says, “is key to maximum impact.”
Ultimately, Gradinaru says she hopes these tools will inspire non-invasive therapies that can repair faulty brain circuits and address issues such as neurodegeneration.
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The Innovators in Science Award Honorees are Breaking New Ground in Neuroscience: Dr. Ben Barres inspired many with his continued efforts, in the face of his own battle with pancreatic cancer.
Published May 1, 2018
By Anni Griswold
Albert Einstein reportedly once said, “Not everything that can be counted counts, and not everything that counts can be counted.” Though the 2017 honorees of the Innovators in Science Award have plenty of countable achievements, their stories reveal a common thread — creative approaches to their work and the development of disruptive tools that transformed scientific understanding in their discipline.
Uncovering a New Role for Glia Cells: Shaping the Neural Communication Network
Ben Barres
Before Ben Barres, MD, PhD, began studying glia — cells that safeguard and anchor neurons — they were thought to play a relatively minor role in the nervous system. But Barres’ work revealed that glial cells, which far outnumber neurons, serve a more important function.
“Ben pioneered the idea that glia play a central role in sculpting the wiring diagram of our brain and are integral for maintaining circuit function throughout our lives,” said Thomas Clandinin, PhD, and professor of neurobiology at Stanford in a university press release. Clandinin was a colleague of Barres, who passed away in December 2017.
Dr. Barres inspired many with his continued efforts, in the face of his own battle with pancreatic cancer, to advance therapies for neurodegenerative disease. His obituary outlines more about his accomplished life and career.
Barres, a Senior Scientist Finalist and former Chair of Neurobiology at Stanford, began his career as a clinical neurologist. He eventually became disillusioned by the medical field’s poor understanding of neural degeneration. While reviewing pathology slides, he found that degenerating brain tissue was often surrounded by a high density of unusually shaped glial cells.
He pursued a PhD and eventually characterized three types of glial cells, revealing how they shape electrical signal transmission. He shared the tools and reagents for cloning these cells, sparking widespread interest in glial function.
Barres’ most recent work showed that rogue glial cells drive neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, a finding he described as “the most important discovery my lab has ever made.”
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The Innovators in Science Award Honorees are Breaking New Ground in Neuroscience: Dr. David Julius takes a molecular approach to explore compound structures.
Published May 1, 2018
By Anni Griswold
Albert Einstein reportedly once said, “Not everything that can be counted counts, and not everything that counts can be counted.” Though the 2017 honorees of the Innovators in Science Award have plenty of countable achievements, their stories reveal a common thread — creative approaches to their work and the development of disruptive tools that transformed scientific understanding in their discipline.
Pain Relief Begins with Basic Science
David Julius
In a field as urgent and divisive as pain control, the race to market new drugs often overshadows a slower yet essential expedition: curiosity-driven science. But in David Julius’ lab at the University of California, San Francisco, curiosity has always been king.
As a graduate student in the early 1980s, Julius, a Senior Scientist Finalist, became fascinated with neurotransmitter systems. He read every paper he could find about the effects of psychoactive drugs on the nervous system. This included works by Timothy Leary and Sol Snyder. Eventually his curiosity led him to clone the serotonin receptor, a groundbreaking feat that introduced molecular biology into the field of pain research, long dominated by physiologists, pharmacologists and psychologists.
In the years since, he has taken a molecular approach to explore how plant-derived products such as capsaicin from chili peppers and menthol from mint leaves “tickle the pain pathway.” His findings have shed light on various pain receptors in the brain and uncovered ion channels that regulate sensory neurons in response to thermal or chemical stimuli.
“If any of these lead to a new pain drug, I’ll be incredibly gratified by that,” says Julius, PhD, a professor of physiology. “But in the end, these [new drugs] arise from asking basic questions about somatosensation and pain. It’s important to keep that in mind, because you never know when a basic discovery will transform an area.”
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The Blavatnik Family Foundation Hosts the UK’s First Blavatnik Awards Ceremony at London’s Victoria and Albert Museum in Collaboration with The New York Academy of Sciences
Published March 7, 2018
By Marie Gentile, Mandy Carr, and Richard Birchard
A gala evening celebrating the UK’s most promising young faculty-level scientists, the 2018 Blavatnik Awards for Young Scientists in the United Kingdom, was held on March 7, 2018 at the Victoria and Albert Museum in London. The evening was a glamorous event attended by the UK’s top leaders in science, business, and philanthropy.
The Blavatnik Awards, established by the Blavatnik Family Foundation in the United States in 2007 and administered by The New York Academy of Sciences, celebrate the past accomplishments and future potential of young faculty researchers, aged 42 years and younger.
These awards recognize scientists working in three disciplinary categories of science: Life Sciences, Chemistry, Physical Sciences & Engineering.
This occasion marked the inaugural year of the Awards in the UK.
Distinguished guests that attended the ceremony included Chief Medical Officer for England, Prof. Dame Sally Davies; ethologist and author, Richard Dawkins; Chief Executive of the British Association for the Advancement of Science, Ms. Katherine Mathieson; 2014 Nobel Laureate Prof. John O’Keefe, 2017 Nobel Laureate Prof. Richard Henderson.
In each category, two Finalists were awarded medals plus a prize of $30,000 and one Laureate in each category was awarded a medal and a prize of $100,000. Sir Leonard Blavatnik presented medals to the three Laureates and six finalists:
Clare Gray, of the University of Cambridge, introduced 2018 Blavatnik Awards UK Laureate in Chemistry Prof. Andrew L. Goodwin of University of Oxford and his work on ground-breaking research in theoretical and applied studies of disorder and flexibility in materials.
Sir Richard Friend, from the University of Cambridge, introduced 2018 Blavatnik Awards UK Laureate in Physical Sciences & Engineering, Prof. Henry Snaith, also of University of Oxford, and highlighted his research in developing new, low-cost and high-efficiency solar cells based on metal halide perovskite materials.
Veronica van Heyningen, Honorary Professor at University College London and University of Edinburgh, introduced 2018 Blavatnik Awards UK Laureate in Life Sciences, Dr. M. Madan Babu of the Medical Research Council (MRC) Laboratory of Molecular Biology, with the award for his insights into the structural biology and molecular logic of key proteins and protein motifs, including GPCRs [G-protein Coupled Receptors] and intrinsically-disordered protein regions.
On November 29, 2017, Takeda Pharmaceutical Company Limited and the New York Academy of Sciences hosted the inaugural Innovators in Science Award Symposium. The event showcased the research accomplishments of the 2017 Innovators in Science Award Honorees in neuroscience and distinguished researchers who are transforming the therapeutic landscape for neurological disease. Topics included advances in optogenetics; microglia and the role of the brain’s innate immunity in diseases including Alzheimer’s disease; advances in designing organoid systems to model complex neurodevelopmental disorders; and efforts to blend big data and systems biology to better understand the genetic drivers and heritability of autism.
Speakers
Michael Halassa, MD, PhD Massachusetts Institute of Technology
Viviana Gradinaru, PhD California Institute of Technology
David Julius, PhD University of California, San Francisco
Frederick Christian Bennett, MD Stanford University Medical School
Shigetada Nakanishi, MD, PhD Suntory Foundation for Life Sciences Bioorganic Research Institute
Rudolph E. Tanzi, PhD Harvard University
Paola Arlotta, PhD Harvard University
Daniel Geschwind, MD, PhD University of California, Los Angeles
Sponsors
Early-Career Scientist Award Honoree Lectures
Speakers
Michael Halassa, MD, PhD Massachusetts Institute of Technology
Viviana Gradinaru, PhD California Institute of Technology
Highlights
In conjunction with the prefrontal cortex, the thalamus plays an essential role in forming and applying abstract associations.
Modulating thalamic activity may have therapeutic benefit in neuropsychiatric disorders such as schizophrenia and autism.
Advances in optogenetic technologies allow researchers to map long-range pathways in the brain—an important step toward developing new therapies as well as understanding the impact of existing therapies including deep brain stimulation.
Customized viral vectors capable of delivering actuator genes to the brain via the circulation are a potential means for non-invasive neural modulation.
Rethinking the Thalamus
Michael Halassa opened the Symposium with the first of two presentations from early-career scientists whose findings hold promise as the basis of future therapies.
Halassa’s work challenges conventional beliefs about the role of the thalamus, suggesting that rather than a simple relay for delivering sensory information to the brain’s cortex, the region is a “superhighway” that facilitates the application of abstract associations formed in the prefrontal cortex. The ability to capture information about the outside world, organize and preserve it hierarchically, and apply those associations in real-time form the basis not only of perception, but of higher-order skills such as prediction and storytelling. Halassa explained that dysfunction in these uniquely human mechanisms underlie schizophrenia, autism, and other neuropsychiatric disorders. Understanding the role of the thalamus in these processes may lead to new therapies and novel approaches to cognitive enhancement.
While the thalamus is, indeed, a sensory relay, only a small portion of the structure is responsible for these functions, while most play no role in sensory processing, Halassa explained. The mediodorsal thalamus (MD) is involved in working memory and other cognitive tasks, and is strongly connected to the prefrontal cortex, the seat of executive functioning and decision-making. Experiments in mice reveal that the thalamus is a critical conduit for interaction between sensory information entering the thalamus and abstract thoughts and associations in the prefrontal cortex.
Mice were trained to associate sensory stimuli—in this case, two distinct sounds—with a specific task directive. One sound indicated that the mouse should respond to a visual cue, the other indicated attention to an auditory cue. Using optogenetics to visualize and modulate regions of the thalamus and prefrontal cortex, the researchers discovered that the process of turning a sensory stimulus into a behavioral rule relies on input from the prefrontal cortex. When either the prefrontal cortex or the thalamus is inhibited, mice can no longer direct their attention accordingly— the ability to tap into the association and follow the rule is impaired.
Mice do not respond to sound cues associated with task rules outside of the experimental environment.
Patterns of neuronal activity show that while the prefrontal cortex is critical for forming associations, the thalamus sustains them. “Signals in the thalamus unlock associations and encode context, which allows the brain to be flexible depending on the circumstances,” said Halassa. When mice were given the same sound cues outside the experimental environment, they make no association. “Different stimuli have different meanings depending on the context, and we see this in everyday life—if you see a red light while you’re driving, you stop. If you see a red light at a dance club, you don’t,” he explained.
Pharmacologic enhancement or dampening of thalamic function may hold promise as a means to address the dysfunctions in contextualization and abstract associations seen in schizophrenia and other psychiatric disorders.
New Approaches to Visualizing and Controlling Brain Circuity
Optogenetic tools have allowed researchers to visualize and control the complex circuitry of the brain. Despite these advances, much remains unknown about the neural paths that influence behavior and brain function in health and disease. Viviana Gradinaru, winner of the Early-Career Scientist Innovators in Science Award, discussed cutting-edge refinements to optogenetic techniques that, combined with modern tissue-clearing methods, enable the type of detailed neural mapping critical to harnessing the brain’s circuitry to treat disease.
Microbial opsins, the light-sensitive proteins that make optogenetics possible, can often be adapted to function in mammalian cells with relative ease. “It’s remarkable, when you think about what a big ask it is for these sequences to function the way we want them to,” said Gradinaru, noting that in their native hosts, such proteins enable entirely different functions, such as locomotion. As optogenetics applications have expanded, however, Gradinaru and others have tweaked the sequences and packaging of these workhorse proteins to increase precision, tolerability, functionality, and to devise new means of delivery.
Gradinaru is developing tools capable of illuminating the brain’s long-range pathways. Mapping the fine projections of the brain poses significant challenges: slicing the tissue can compromise reconstruction of the pathways, and the poor optical properties of lipid-rich brain tissue make imaging difficult. In a significant step toward solving these problems, Gradinaru revived the century-old technique of tissue clearing, adding modern improvements that dissolve light-scattering lipids while locking proteins and nucleic acids in place within a hydrogel matrix that preserves structure. The resulting tissue is both transparent and capable of retaining colored labels. Used in tandem with a new class of optogenetic tools, this tissue-clearing technique enables researchers to track individual axons, even through tightly packed bundles.
New visualization protocols combining whole body tissue clearing with custom viral vectors that deliver genes systemically and allow for cell type-specific expression facilitate high-resolution, intact neural circuit mapping.
Viral vectors are a common means of introducing labels, sensors, and actuators into the brain, typically via intracranial injection, a method that is invasive and often results in non-homogeneous expression over limited tissue volume. “But what if we could use the vasculature to deliver labels brain-wide, and devise a way to control the density of the labels?” Gradinaru asked, noting that the major hurdle to delivering opsins to the brain is finding a vector capable of circumventing the blood-brain barrier. Using directed evolution, Gradinaru and her team at Caltech engineered a strain of a common viral vector. The adeno-associated virus is capable of passing through the blood-brain barrier and delivering a customized package of protein sequences and gene-regulatory elements that allow researchers to refine a target and restrict expression to certain cell types. It is also possible to limit expression within a cell type, which reduces the density of the label and allows for more precise observations. “We can systemically deliver various colors and direct their expression in the brain, then clear the tissue and reconstruct the morphology to see the long-range projection pathways,” said Gradinaru. Looking to the future, she envisions systemically delivered genes (e.g. actuators or editing tools) as a non-invasive method of modulating neuron biochemistry and activity.
David Julius, PhD University of California, San Francisco
Frederick Christian Bennett, MD Stanford University Medical School
Shigetada Nakanishi, MD, PhD Suntory Foundation for Life Sciences Bioorganic Research Institute
Highlights
Studies of mechanisms by which natural compounds such as capsaicin and menthol modulate temperature-sensitive ion channels in the peripheral nervous system are leading to greater understanding of pain perception.
Recent experiments reveal that while microglia lose expression of highly specific, signature genes in culture, reintroduction to the CNS environment induces their re-expression and a return to functionality, hinting at the possibility for microglial transplant as a therapy for diseases including Alzheimer’s.
Discoveries over the past three decades have revolutionized our understanding of neurotransmitter-receptor interactions and the role of these pathways in health and disease.
Probing the Pain Pathways
David Julius began a session of presentations by senior scientist honorees with a discussion of pain pathways—crucial protective mechanisms that often go awry, resulting in prolonged suffering and disability. According to Julius, pain is the primary reason patients seek medical help, and in the United States alone, up to 100 million people suffer some form of persistent pain.
Elucidating the mechanisms of pain—particularly those that drive the shift from acute pain, which is purposeful, to chronic pain, which can persist long after injury subsides—is key to understanding how to address and prevent persistent pain syndromes. A family of cation ion channels, the Transition Receptor Potential or TRP channels, play major roles in sensory physiology, facilitating detection of a wide range of both endogenous and exogenous stimuli including temperature, pressure, chemical irritation, and inflammation. Julius discussed his lab’s discoveries about the structure, functionality, and modulation of a subset of TRP channels tied to temperature and/or chemical sensitivity: TRPV1, TRPM8, and TRPA1.
Julius and his collaborators turned to nature for both inspiration and information to guide their research, focusing on several of the plant kingdom’s natural defense mechanisms: the potent chemicals capsaicin, which produces the sensation of heat in chili peppers; menthol, the cooling agent in mint oils; and thiosulfinates, pungent compounds found in onion and garlic. These “homegrown chemical warfare agents” ward off predators by producing an acute pain response, and it is the impact of these chemicals on TRP channels that form the basis of research that is answering foundational questions about the mechanisms and structure of these complex cellular sensors and their role in pain signaling.
Heat, Cold, Pain, Pressure
Two of the ion channels studied, TRPV1 and TRPM8, are temperature sensors, with the former activated by heat and the latter by cold. Experiments show that TRPV1 can be activated chemically by capsaicin, but also by changes in ambient temperature. “The channel is quiet at body temperature, but at about 43 degrees, it strongly activates,” said Julius. “Interestingly, this is the psychophysical threshold at which most of us discriminate between an innocuously warm object versus one that’s noxiously hot.”
TRPV1 and TRPM8 are triggered by changes in ambient temperature.
Conversely, TRPM8 is activated at temperatures below 25 degrees, as well as by exposure to menthol. In a physiologic twist, actual sensations of cold and heat and chemical compounds that mimic cold and heat are perceived similarly by the peripheral sensory nervous system. Further studies reinforce that these proteins are intrinsically temperature-sensitive, and serve as molecular thermometers essential for detecting and responding to temperature shifts. To wit: mice bred without a TRPM8 gene are unable to distinguish between a warm compartment and an uncomfortably cold one.
TRPV1 can also be modulated by components of the body’s “inflammatory soup,” explained Julius, noting that while some modulators, including extracellular protons and some lipids, bind directly to the channel and lower its threshold for detecting heat, other modulators, such as prostaglandins and peptides, act on their own receptors yet have the same threshold-lowering effect on TRPV1. “Understanding how these allosteric components directly or indirectly act on the receptor to change its threshold is a step toward developing drugs that interfere with the ability of these modulators to over-sensitize the channel and contribute to persistent pain syndromes,” Julius said.
Modeling the Channel
A lack of high-resolution atomic structural information has hindered researchers’ efforts to fully understand the functionality and modulation of TRP channels. Julius described how cryo-electron microscopy has yielded the first three-dimensional models of TRP channels and allowed researchers to observe the channels’ gating mechanisms in response to multiple stimuli. Imaging reveals that TRP channels have two operable gates which control ion flow, with some modulators acting specifically on one gate or the other. Julius believes this structure contributes to the channels’ sensitivity and efficiency as sensors. “This suggests that part of the reason TRP channels function so beautifully as polymodal signal detectors is that this two-gate mechanism allows for very rich physiologic modulation,” he said.
More recently, Julius and his collaborators have begun to study TRP channels embedded in lipid nanodiscs, which mimic the native environment of the body. Doing so allows them to visualize the precise location where molecules bind to the channel, including toxins and small molecules—an important step in designing next-generation analgesic drugs to modulate the activity of these channels.
Origin, Environment, and Microglial Identity
Frederick Christian Bennett addressed the Symposium on behalf of the late Ben Barres, Senior Scientist Award finalist. Bennett began with an homage to his mentor, highlighting the pioneering neurologist and neuroscientist’s contributions to discovering the dual role of astrocytes—as critical facilitators of synapse formation and functioning in health, and as highly reactive synapse-and neuronal destroyers in certain stress or disease states. “Glial cells and brain function are intimately intertwined in complicated ways we are just beginning to understand, and which hold enormous potential as treatment targets,” Bennett said, transitioning into a discussion of his own research, which also centers on a type of glial cell—microglia.
Microglia are macrophages often referred to as the resident immune cells of the central nervous system. Arising from the yolk sac early in fetal development and quickly sequestered inside the brain, microglia have an origin unlike other hematopoietic cells in the body, which arise in the bone marrow and differentiate throughout the body. Like astrocytes, microglia are dynamic cells capable of changing state based on context and environment, and much the way astrocytes assume a reactive state in diseases such as Alzheimer’s, ALS, and multiple sclerosis, microglia too become dyshomeostatic in disease.
Until recently, in-depth studies of microglial cell function have been complicated by an inability to distinguish them from other macrophages in the brain. However, microglia express a series of signature genes that differ from those expressed by other macrophages. Antibody-based techniques that bind to TMEM119, a protein highly specific to microglia, have yielded new insights into these unique cells. By tracking expression of TMEM119, Bennett is investigating how the CNS environment impacts microglial function and gene expression, and whether microglial cell transplant may be a viable treatment strategy for brain diseases.
Bone marrow transplants are already used to treat certain disorders that impact brain function, with the goal of introducing hematopoietic cells that will infiltrate the brain and differentiate into healthy microglial cells to replace those malfunctioning due to disease or mutation. Yet, studies show that while stem cells do enter the brain and differentiate into cells that are “microglia-like,” they are not true microglia and do not express TMEM119 or other signature microglial genes. The concept of a true microglial cell transplant is one Bennett deems “provocative,” and despite the early stage of the research in animal models, promising.
Bennett’s research shows that the unique ontogeny of microglia, along with elements of the CNS environment, have a profound influence on the cells’ identity and function. Experiments with cultured mouse microglia reveal that these cells lose all expression of signature genes, including TMEM119, when removed from their native environment. Conversely, in a surprising display of plasticity, cultured microglia resume normal gene expression when returned to the CNS. “Signals in the brain are sufficient to sustain, induce, and re-induce microglial identity,” Bennett said. “We didn’t know that it was possible to take cells out of the brain, reintroduce them, and have them recover their homeostatic state.” He explained that such findings may upend notions about the state of microglia in diseases such as Alzheimer’s. For example, it has been posited that in a CNS environment rendered abnormal by disease, microglia may enter an irreversibly neurodegenerative state. The ability of microglial cells to change gene expression and functionality based on their environment suggests that perhaps changes to the CNS in brain disease may restore microglial function.
Some of the most fundamental insights about the molecular mechanisms that facilitate communication between neurons have emerged from the work of Shigetada Nakanishi. In a career spanning five decades and counting, Nakanishi has discovered and elucidated the roles for multiple families of neurotransmitters, including the ubiquitous excitatory amino acid glutamate, which is critical for neural plasticity, learning, and memory tasks. In excess, glutamate is also implicated in neurodegenerative disorders.
Glutamate receptors are categorized as either ionotropic, meaning they directly and rapidly control ion flow by opening or closing pores in the neuronal cell membrane; or metabotropic, meaning they act on signaling pathways within the nerve cell. These characterizations were discovered using a technique Nakanishi pioneered to circumvent a major hurdle facing early studies of neurotransmitters. Namely, the substances were simple to extract and study, but the receptors, buried deep within cell membranes, eluded extraction and cloning. Nakanishi’s method, which used electrophysiology to measure expression of glutamate receptors in Xenopus oocyte cell membranes, yielded the molecular identities of more than a dozen subtypes of ionotropic glutamate receptors and eight metabotropic subtypes. In the decades that followed, he has demonstrated the role of various receptors in facilitating key brain functions and behaviors, including responding to reward-seeking or aversive stimuli and discriminating between the presence or absence of light.
Nakanishi described experiments targeting the dopamine pathways that control reward-based learning in the basal ganglia to better understand how these two morphologically similar but functionally distinct pathways modulate reward-seeking and aversive reactions. Rewarding or aversive stimuli enter the nucleus accumbens via glutamate transmission, and these inputs are further transmitted along two parallel pathways—the direct pathway, characterized by neurons that express excitatory D1 dopamine receptors, and the indirect pathway, packed with neurons that express inhibitory D2 receptors. “These pathways modulate behavior through dopamine transmission, but in opposite ways,” said Nakanishi.
Glutamate receptors facilitate transmission along separate and opposing pathways in both the retinal and the striatal neural networks. The result is the ability to discriminate between light and darkness, and to interpret stimuli as either rewarding or aversive.
Nakanishi and his collaborators used tetanus toxin to selectively and reversibly block each transmission pathway, discovering that the direct pathway (D1) increases dopamine levels and is responsible for processing rewarding stimuli, while the indirect (D2) pathway processes aversive stimuli and reduces dopamine transmission. More advanced studies of this phenomenon revealed that rewarding and aversive stimuli are converted to activation of excitatory D1 receptors and suppression of inhibitory D2 receptors, respectively; this conversion commonly activates the cAMP-protein kinase A signaling cascade and in turn, stimulates glutamate transmission in a stimulus-dependent, pathway-specific manner.
A similarly structured neural transmission network governs the discrimination between light and dark in the retinal network, explained Nakanishi. Here too, stimulation of highly specific and opposing receptors—AMPA and mGLUR6, both glutamate receptor subtypes—results in the ability to distinguish light and dark signals.
He noted that imbalances in neurotransmitters and functioning of their receptors are implicated in both organic brain diseases and psychiatric diseases, including depression. Illuminating complex neurotransmitter-receptor interactions is critical for understanding healthy brain function as well as the origin and progression of disease, and is fundamental to drug development, as many drugs act directly on receptors.
Amyloid deposition begins 10–15 years before patients present with symptoms of Alzheimer’s disease, indicating a need for early identification and treatment of at-risk patients.
Three-dimensional neural cell cultures that recapitulate Alzheimer’s disease in a dish are facilitating the identification of compounds that prevent or slow the formation of plaques and tangles.
Beta amyloid is a powerful anti-microbial peptide, and emerging research points to the protein’s immune function as a possible factor in “seeding” plaques that can ultimately lead to Alzheimer’s.
From Rudolph Tanzi’s perspective, the five million patients in the United States with Alzheimer’s are only the tip of the iceberg when it comes to the true scope of the disease. “Plaques begin to form 10–15 years before patients present with symptoms, so that’s potentially 20 or 25 million people who are on the path toward a diagnosis,” said Tanzi, emphasizing that unlike heart disease or cancer, Alzheimer’s disease (AD) requires patients to present with symptoms before treatment begins. “Imagine if we waited until cancer was symptomatic before we treated it?” he said. “Trying to treat plaques once someone has dementia is like trying to put out a forest fire by blowing out the match.”
Tanzi is a co-discoverer of the early-onset familial Alzheimer’s genes, and 30 years after these initial discoveries, the field of genomics has been transformed through advanced sequencing techniques. These techniques allow researchers to identify areas of the genome where AD genes reside as well as mutations that, when studied in mice and in cultured human nerve cells, are leading to next-generation therapeutics aimed at preventing or halting disease progression. Over the past decade, Tanzi and others have built an ever-growing list of more than 200 AD-related mutations impacting one or more aspects of the “trilogy of pathology” underlying Alzheimer’s—amyloid plaques, tangles, and neuroinflammation.
Attempts to recreate Alzheimer’s in mouse models has done little to shed light on the interplay of these factors in causing AD, but in recent years, the advent of brain organoids—human stem cell-derived neural culture systems—has facilitated the creation of what Tanzi terms “Alzheimer’s in a dish.” For the first time, researchers can observe a disease progression that typically takes more than a decade in a matter of weeks. Tanzi reported that by 7 weeks, cells expressing APP or presenilin mutations develop both plaques and tangles, presenting an unprecedented opportunity to test the results of various interventions on the disease process.
Human neural cultures of Alzheimer’s disease, or “Alzheimer’s in a dish” are an efficient, effective method for screening compounds that may impact AD pathogenesis, such as those that inhibit the formation of neurofibrillary tangles.
Blocking amyloid deposition through beta or gamma secretase inhibitors successfully reduces the incidence of plaques but also, notably, blocks the formation of tangles—firm proof of the long-debated “amyloid hypothesis,” or the notion that amyloid itself is the driver of AD. Tanzi and his collaborators have also used this model to test compounds that effectively block tangles, identifying 30 FDA-approved drugs that inhibit tangle formation, and another 8 that reduce amyloid deposition, and thus block tangles.
Neuroinflammation is the least-studied factor in AD pathogenesis, yet it warrants greater attention. Tanzi explained that brains that are resilient to Alzheimer’s—those replete with plaques and tangles that never cause dementia—are united by a common feature: a lack of inflammation. “You can have lots of plaque and tangles, but if the brain’s immune system doesn’t react to them with gliosis, you can escape dementia,” he said. Genes including TREM2 and CD33 are implicated in the neuroinflammatory process by regulating the activity of microglial cells. Mutations or knockouts of these genes can impair microglial plaque clearance as well as promote pro-inflammatory changes in these critical immune cells.
Tanzi concluded by describing recent studies that reveal a surprising dual role for beta amyloid, not only as a pathogenic protein in AD but also as an anti-microbial peptide and an essential component of the brain’s innate immunity. The tendency of amyloid beta to form plaques, viewed as inherently pathological in AD, is a powerful protective mechanism when viewed in an immune context. The protein binds to carbohydrates on microbial surfaces, agglutinates, and ultimately traps invading pathogens within a plaque. When HSV1 and Salmonella are introduced into mouse brains, beta amyloid deposition skyrockets, forming plaques in as little as 24 hours. “It’s still early days for this research, but it may be that microbes are seeding amyloid deposition in the brain. This is an entirely different way to look at the origin of Alzheimer’s,” Tanzi said.
AJNR Am J Neuroradiol. 2008 Jan;29(1):18-22. Epub 2007 Oct 9.
Neuropsychiatric Diseases
Speakers
Paola Arlotta Harvard University
Daniel H. Geschwind University of California, Los Angeles
Highlights
Long-cultured brain organoids differentiate into many cells types, including light-sensitive retinal cells and neurons with dendritic spines.
Organoids can be used to model highly penetrant single mutations that impact neurodevelopment, and will soon be a viable method for creating models of polygenic disorders in culture.
Autism is one of the most heterogeneous neurodevelopmental disorders, encompassing a wide range of phenotypes and a large and rapidly growing number of associated genetic mutations.
Analyses incorporating genetic, transcriptomic, and phenotypic data are revealing patterns of gene expression in autism, as well as linkages to neuropsychiatric disorders including schizophrenia and bipolar disorder.
Building the Brain: From Embryo to Organoid
“How can we model hugely complex diseases like autism, schizophrenia, and other disorders that impact aspects of personality and behavior that are uniquely human?” asked Paola Arlotta, describing the difficulty of unraveling the mysteries of neurodevelopmental disorders. “If we want to look at the impact of the whole genome on disease, we can’t use an animal model—we need a human model,” she said. Arlotta’s lab builds brain organoids—organ models cultured from embryonic or pluripotent stem cells—to understand both normal and atypical brain development in unprecedented detail.
Organoids are a relatively new but promising model for investigating brain development and neurodevelopmental disorders, but until recently, the lifespan of an organoid was measured in weeks. Thanks to modifications in the protocols, Arlotta’s lab is building brain organoids that grow for nine months or longer, maturing and diversifying into an array of cell types and providing new insights into the human neurodevelopmental process.
Much of this insight has been gleaned through single-cell studies of more than 80,000 cells taken from 30 organoids and examined for cell type classification, patterns of gene expression, and physical characteristics. Arlotta and her primary collaborator, postdoctoral fellow Giorgia Quadrato, reported the discovery of a surprising array of cell types, including astrocytes, radial glia, excitatory and inhibitory neurons, retinal cells—including photoreceptor-like cells that respond to light—and progenitors of the cerebral cortex. While little is known about the patterns of gene expression in cells of the fetal human brain, comparisons of the various cell types identified within the organoids with the limited existing data show high correlation between the cells in the organoid and endogenous fetal brain cells. “With no instruction from the outside, these organoids self-organize and mimic the process of human brain development, including differentiating into these various cell lineages,” Arlotta said. “It really speaks to the power of what’s encoded in the genome.”
Cell samples from 8-month-old organoids strongly recapitulate both cell type diversity and patterns of gene expression seen in endogenous fetal brain cells.
In a subsequent set of findings that stunned both Arlotta and her collaborators, cells from an 8-month-old organoid were shown through electron microscopy to contain dendritic spines, indicating a level of cell maturity difficult to achieve in culture. Psychiatric diseases including schizophrenia are tied to synaptic dysfunction and errors in dendritic pruning, thus the ability to grow cells that form true spines in a dish may present new avenues for exploring genetic drivers of these diseases as well as potential treatments.
“We are heading toward a future where we can engineer highly penetrant mutations into pluripotent stem cells, grow an organoid, and use single-cell sequencing to understand what cell types and pathways are affected by that mutation,” Arlotta said. Noting that most neurodevelopmental diseases are polygenic, she also emphasized the potential for creating chimeric organoids that express different mutations and can be grown from human cells with any genetic background. “An individual’s genomic background is fundamental in controlling the outcome of a mutation, and we’ll soon be able to use organoids to observe how the genome modulates the effect of a certain mutation,” she said.
Autism: Genes, Heritability, and Risk
Daniel Geschwind delivered the final research presentation of the Symposium—a brief but intense dive into efforts to discover the genetics of perhaps the most heterogeneous neurobiological disorder: autism.
Geschwind applies a systems biology approach to the challenge of identifying causal genetics and heritable risk of a disorder that, unlike neurological diseases, evidences no physical manifestations of pathology. Autism is diagnosed based on observations of behavior and evidence of deficits in social interaction and communication, and the disorder encompasses a wide range of phenotypes. Geschwind is building data sets including genetic, transcriptomic, and phenotypic information in an attempt to uncover and understand the linkages between the many manifestations of autism, as well as its connection to other neurodevelopmental and neuropsychiatric disorders.
Geschwind explained that autism is largely driven by common genetic variants, along with some rare de novo mutations, yet no specific gene accounts for more than 1%–2% of cases. A decade ago, fewer than 10 genes were associated with autism, but due to a surge of research interest in the disorder, which affects 1 in 68 children in the United States, more than 200 autism-associated genes have now been identified. Geschwind expects that number to quickly rise to at least 1,000. Due in part to this extreme genetic variability, he and his collaborators are probing the transcriptome in search of patterns of gene expression and regulation that may transcend the genetic and phenotypic heterogeneity of autism.
Comparisons of cortical tissue in autistic and neurotypical brains reveal distinct differences in patterns of co-expression in genes that drive corticogenesis and synaptic function “Most of these genes are expressed at high levels in fetal development, which tells us that a good deal of autism risk that we can identify is occurring during fetal brain development, and that’s quite important,” said Geschwind. Notably, brains of people diagnosed with autism are characterized by downregulation of genes associated with synaptogenesis, and upregulation of genes that regulate microglia and astrocyte activity. As glia are critical for synaptic plasticity, Geschwind believes that this abnormal upregulation of their activity may promote a dyshomeostatic environment that impairs synaptic function in the autistic brain. “It’s also possible that what we see as an upregulation may just be the failure of the neurotypical downregulation of these genes in the first decade of life, so it’s possible that there’s a treatment window there,” Geschwind said.
Advances in sequencing and a surge of interest in ASD have led to the identification of more than 200 gene mutations associated with autism, none of which accounts for more than one percent of cases and many of which have strong pleiotropy.
Transcriptomic comparisons between autism and psychiatric disorders including schizophrenia, bipolar disorder, and depression provide additional insights regarding the correlation of disorders that are clinically distinct yet show strong co-heritability. Geschwind described overlaps in gene expression in autism and schizophrenia, as well as in schizophrenia and bipolar disorder—similarities that lay, in part, in the common upregulation of astrocytes and/or microglia in these disorders.
Ascertaining the impact of specific autism-association mutations on neurodevelopment requires a new generation of tools that faithfully recreate in vivo neurodevelopment in vitro or in silico. Geschwind described how machine learning algorithms and 3D neural cell cultures—brain organoids—are advancing the quest to understand the interplay of these complex factors.
Henry Snaith, PhD Professor of Physics, University of Oxford
Prof. Snaith has striven to develop new photovoltaic technologies based on simply processed materials, which have promised to deliver solar energy at a fraction of the cost of incumbent silicon modules.
Through a series of key discoveries, he found that metal halide perovskite materials, which had been overlooked for decades because of their very low photovoltaic energy efficiency, can be employed in highly efficient solar cells. He has developed a low-cost synthesis method for the perovskite solar cells, and significantly raised their energy efficiency from 10.9 percent in his first publication to over 22 percent in a single junction perovskite solar cell, and more recently to 25 percent by combining perovskites with silicon solar cells.
Currently, he is pushing the perovskite-on-silicon tandem cells to surpass the 30 percent efficiency mark, making them very promising for industrial applications. He has also significantly improved long-term stability of perovskite solar cells and discovered numerous key fundamental aspects of the perovskite semiconductors, which helped broaden the application range of these materials to include light emission, radiation detection, memory and sensing.
Prof. Snaith’s work toward a significant cost reduction in photovoltaic solar power could help propel society to a sustainable future.
Physical Sciences & Engineering Finalists
Claudia de Rham, PhD Reader in Theoretical Physics, Imperial College London
Dr. de Rham has revitalized massive gravity theory, which is one way of modifying General Relativity to solve the open puzzles of cosmology. The early versions of massive gravity theory had been known for their dangerous pathologies, including a ghost mode and a discontinuity with General Relativity in the limit where the mass of a graviton goes to zero.
In 2010, Dr. de Rham solved such problems by constructing a nonlinear theory of massive gravity, which is ghost free and theoretically consistent. Since this breakthrough, Dr. de Rham has further established the effective quantum theory of massive gravity to describe the accelerated expansion of the universe as a purely gravitational effect, with the role of dark energy being played by massive gravitons.
Her work has continued to define the field beyond Einstein’s theories of gravity and cosmology, and revolutionized our understanding of the fundamental evolution of the universe and the quantum nature of gravity.
Andrew Levan, PhD Professor of Astronomy, University of Warwick
Prof. Levan works on the observation of gamma-ray bursts (GRBs), which are the most luminous and energetic explosions in the universe. He has achieved a new understanding of the rich relativistic physics behind GRBs, and has deployed such phenomena as powerful probes that act as lighthouses to the distant universe.
For instance, a new type of GRB he discovered opened an entirely new window onto the properties of black holes at the center of galaxies. Most recently, Prof. Levan has also played a major role in the characterization of the first electromagnetic counterpart to a gravitational wave source, GW170817. This included the identification of the infrared counterpart and leading the first observations of this counterpart with the Hubble Space Telescope.
These events provide the astrophysics community with a completely new way to study the Universe, and explore new information from deep inside extreme events, places that cannot be seen with normal light.
Chemistry Laureate
Andrew Goodwin, PhD Professor of Materials Chemistry, University of Oxford
Prof. Goodwin is a world leader in the study of the dual roles of mechanical flexibility and structural disorder in the chemistry and physics of functional materials.
Examples of materials that rely on localized disorder to enhance functionality include semiconductors and glass. Goodwin’s laboratory utilizes advanced diffraction and modelling techniques to probe disordered materials and subsequently produce new, tailored materials that display unique properties. Most materials expand upon heating and shrink when compressed; however, Goodwin has discovered that by careful control of the disorder within the structure of a substance, the opposite can occur — materials will shrink upon heating (negative thermal expansion) and expand when compressed (negative linear compressibility).
These counterintuitive processes are useful in the design of heat-resistant materials, advanced pressure sensors, artificial muscles and even body armor. Goodwin has also played a key role in the structural analysis of amorphous materials using total scattering methods, which, in the case of amorphous calcium carbonate, the key structural component in bones and shell, led to a complete understanding of the ability of organisms to nucleate different crystalline structures from the same biomineral precursor.
Chemistry Finalists
Philipp Kukura, PhD Professor of Chemistry, University of Oxford
Prof. Kukura develops and applies novel spectroscopic and microscopic imaging techniques with the aim of visualizing and thereby studying biomolecular structure and dynamics.
Of particular importance are Prof. Kukura’s recent breakthroughs in scattering-based optical microscopy, where his group was the first to demonstrate nanometer-precise tracking of small scattering labels with sub-millisecond temporal resolution, which enables highly accurate measurements and mechanistic insight into the structural dynamics of biomolecules such as molecular motors and DNA. His group was also able to develop ultrasensitive label-free imaging and sensing in solution, down to the single molecule level, which has the potential to revolutionize our ability to study molecular interactions and self-assembly.
The Kukura group continues to challenge what we believe we can measure and quantify with light and use it to improve our understanding of biomolecular function. Ultimately, this technology has the potential to enable a variety of universally applicable and quantitative methods to probe molecular interactions at the sub-cellular level.
Robert Hilton, PhD Reader, Department of Geography, Durham University
Dr. Hilton’s research has provided new insights on Earth’s long-term carbon cycle and the natural processes that transfer carbon dioxide (CO2) between the atmosphere and rocks. His research has uncovered how erosion of land in the form of geomorphic events (earthquakes and resulting landslides), weathering of organic carbon in rocks, and the export of carbon by rivers can impact atmospheric CO2 concentration. Dr. Hilton and colleagues have developed geochemical and river sampling methods which allow this to be done.
The release of CO2 into the atmosphere through the actions of humans burning fossil fuels has become a concern in recent decades. Dr. Hilton’s research highlights that the natural rates of this process (by weathering and breakdown of rocks) is much, much slower. The planet is currently undergoing dramatic changes with respect to global climate, and it is crucially important to consider whether these aspects of the carbon cycle may amplify human impacts.
Life Sciences Laureate
M. Madan Babu, PhD Programme Leader, MRC Laboratory of Molecular Biology
Dr. Babu’s multi-disciplinary work employs techniques from data science, genomics and structural biology to analyze biological systems. Using this innovative approach, Dr. Babu has made important discoveries about proteins called G-protein-coupled receptors (GPCRs). These proteins are implicated in numerous human disorders, and drugs targeting GPCRs represent nearly 30 percent of all drug sales.
Dr. Babu has shown that many GPCRs targeted by common drugs can differ significantly from one person to another, so patients with different versions of the same GPCR are likely to have different responses to the same drug. These findings will begin to identify problematic treatments, and could potentially revolutionize personalized medicine. In a parallel body of work, Dr. Babu has also made fundamental discoveries in the role of so-called “disordered” proteins. About 40 percent of human proteins have a region where the protein becomes more flexible, less structured — these floppy, flexible parts of proteins have puzzled structural biologists for decades.
Dr. Babu and his team have helped to establish the roles of disordered proteins in health and disease. Together, these studies shed light on key types of proteins that are integral to human health.
Life Sciences Finalists
John Briggs, DPhil Programme Leader, MRC Laboratory of Molecular Biology
Dr. Briggs uses and develops state-of-the-art techniques in electron microscopy to understand the structure and functions of biological molecules. He pioneered a technique called cryo-electron tomography (cryo-ET), which allows visualization of biological specimens at near-atomic resolution.
He has combined this technique with other types of microscopy to identify and image rare and dynamic cellular events. Dr. Briggs was the first to achieve pseudo-atomic resolution for visualization of a biological structure using cryo-ET by imaging the capsid domains of HIV. This remarkable achievement revealed the network of protein interactions governing the assembly of HIV particles, and provides new insights into viral function.
Dr. Briggs is at the forefront of structural biology, leading the search for higher resolution visualizations of cellular processes directly within their native environments. By turning these techniques to important biological questions, his work stands to have broad impact on our understanding of the biology of cells and viruses.
Timothy Behrens, DPhil Professor of Computational Neuroscience, Nuffield Department of Clinical Neurosciences Deputy Director, FMRIB Centre, University of Oxford Honorary Lecturer, Wellcome Centre for Imaging Neuroscience, University College London
Prof. Behrens uses mathematical models, behavioral experiments and neural recordings to dissect the biological computations that underlie human behavior. He has uncovered key aspects of how we represent the world around us, make decisions and guide our behavior.
His group has shown that the neural structures used to represent physical space are also used to represent abstract concepts — the brain uses a similar mechanism to encode “maps” of abstract ideas. Such findings have impact on neural network computing and artificial intelligence, but also on our understanding of cognition and mental health. Prof. Behrens has also worked to map the precise anatomy of the human brain, and is leading a large-scale collaboration to map networks of neurons important for cognition.
Few fields are more intimately related to our sense of what it means to be human — and Prof. Behrens and his team are at the forefront of this understanding.
Oded Rechavi, PhD, Senior Lecturer, Department of Neurobiology, Tel Aviv University
Dr. Rechavi’s research upends the traditional laws of inheritance. The notion that traits acquired over the course of a lifetime could influence heredity was heresy until recently, when Dr. Rechavi showed how environmental conditions can imprint “molecular memories” that govern the passage of acquired traits to future generations.
DNA vs Small RNAs
Rechavi’s work in C. elegans, a species of small worms, illustrates how various stressors can induce heritable changes mediated not by DNA, but by small RNAs. By transferring small RNAs from the regular cells of the body that are impacted by the stressor, to the “germline” cells (eggs and sperm) that pass on traits to the next generation, the experiences of one generation can produce long-lasting impacts on gene regulation in multiple subsequent generations.
Rechavi’s lab published the first proofs of this effect, showing that exposing the parent worms to a virus confers immunity on the offspring through the transfer of small RNAs. He later showed that a similar mechanism allows the offspring of starved worms to live longer and to better survive periods of starvation. His group has identified the genes and determined the rules that govern which changes are heritable, as well as the potential duration of that inheritance.
Rechavi has hypothesized that similar mechanisms of small-RNA-based inheritance exist in mammals, including humans. Encompassing genetics, evolutionary biology and developmental biology, Rechavi’s research is fundamental to advancing understanding of the heritability of complex traits and diseases.
Chemistry Laureate
Charles Diesendruck, PhD, Assistant Professor of Chemistry, Technion — Israel Institute of Technology
Dr. Diesendruck works at the intersection of chemistry, physics and materials science, in the recently resurgent field of mechanochemistry. Diesendruck and his collaborators are using mechanically driven reactions to create novel molecules and new materials capable of responding to both physical and chemical stimuli.
As polymers and fiber-composites have become ubiquitous, the tendency of these materials to break, split or otherwise degrade under pressure have limited their application, especially in high-strain environments such as aircraft and automobiles. Diesendruck’s research seeks to better understand how mechanical forces can change molecular bonds and alter the properties of materials, using this knowledge to design resilient, responsive macromolecules for next-generation polymers.
Developing “Smart” Materials
In Diesendruck’s vision, these “smart” materials will be customized with specific stress conduction characteristics, respond productively to mechanical strain, and be able to detect and reinforce or repair structural damage. Diesendruck was among the research team that created the first autonomously “self-healing” fiber-composites, a key step toward producing materials that maximize the benefits of composites, including strength and weight, while minimizing the risks from damage and increasing the longevity of these materials in transportation and other applications.
Diesendruck’s group is also engaged in exploratory research probing difficult or previously inaccessible chemical transformations that may lead to new reactions and reactants.
Physical Sciences & Engineering Laureate
Anat Levin, PhD, Associate Professor, The Andrew & Erna Viterbi Faculty of Electrical Engineering, Technion — Israel Institute of Technology
Prof. Levin is a leader in the emerging field of computational photography, which blends computing with traditional imaging techniques to transcend the limitations of even the most advanced cameras, producing novel imaging results and capabilities. Levin’s work is rooted in discovering mathematical foundations and applying them to solve real-world challenges in imaging and optics.
She is the creator of a prototype computational camera specialized to capture moving objects and scenes, which introduces a constant, quantifiable degree of motion blur during exposure to allow for streamlined blur removal in post-processing. Prof. Levin has also worked to optimize the process of colorizing grayscale images and videos, simplifying a historically time-consuming and expensive process using a method that automatically propagates color among pixels based on the intensity of neighboring pixels.
Using Light Scatter to Study Chemical Composition
Advances in computational photography will have implications that extend well beyond digital photography, including improving medical, microscope and telescope imaging, and ultimately transforming videography. More recently, Levin has published methods for utilizing patterns of light scatter to determine the chemical composition of a material, a technique that could have implications for fields as diverse as ultrasound imaging and air quality assessment.
She has also developed dynamic digital displays that instantly adapt to changes in light and viewing angle, and prototype displays that may ultimately enable large-scale, glasses-free 3D movie viewing.
(Back Row L to R) Ellis Rubinstein, President and CEO, New York Academy of Sciences, Dr. Charles Diesendruck, Technion-Israel Institute of Technology, Prof. Anat Levin, Technion-Israel Institute of Technology, Len Blavatnik, Chairman, Access Industries/Blavatnik Family Foundation, Dr. Oded Rechavi, Tel Aviv University. (Front Row L to R) Nechama Rivlin, First Lady of Israel, Reuven Rivlin, President of Israel, Prof. Nili Cohen, President, Israel Academy of Sciences and Humanities.
