This collection of papers brings together experimental and developmental perspectives on how mathematics anxiety impacts mathematics performance: studies within experimental psychology; studies on neural substrates of mathematics anxiety and its links to mathematics performance, and studies of interventions targeting emotional, behavioural, and cognitive aspects of mathematics anxiety. Importantly, intervention studies, apart from obvious practical benefits, shed unique light on causal mechanisms. The virtual issue is edited by Flavia H. Santos, Ann Dowker, Krzysztof Cipora, and Karin Kucian. See https://nyaspubs.onlinelibrary.wiley.com/doi/toc/10.1111/(ISSN)1749-6632.math-anxiety.
Published since 2008, this series includes scholarly review articles in all areas of addiction science. The series was established and edited by George R. Uhl (New Mexico VA Healthcare System). In 2022, Edythe London (UCLA) became series editor. For more information on past issues, see https://nyaspubs.onlinelibrary.wiley.com/hub/nyaspubs/reviews-series.html.
The Tata Transformation Prize will recognize Indian scientists for research to solve societal needs and promote economic competitiveness
Mumbai, India | 4 January 2023 – Tata Sons and The New York Academy of Sciences today announced the Tata Transformation Prize to recognize and support promising scientists in India who are developing innovative technological solutions to critical societal challenges.
The new prize will be awarded each year to three scientists for innovations in each of three areas: food security, sustainability, and healthcare. Each winner will each receive INR 2 crores, and will be honoured at a ceremony in India in December.
“This prize will accelerate breakthrough innovations by the Indian scientific community,” said Natarajan Chandrasekaran, Chairman of the Board of Tata Sons. “We hope this prize will help bring the transformational work of Indian scientists to light, reward them appropriately, and encourage them in taking solutions to market. The Tata Transformation Prize is one small way in which we will promote science and scientists to solve India’s national problems.”
Award Criteria
Applicants for the prize must be active researchers with a doctoral degree, or equivalent, and be employed by an eligible university, institute, or other research organization in India. Applicants must propose technologies addressing food security, sustainability, or healthcare challenges with a focus on digital and technological transformation. Prize winners will be scientists whose proposed innovations re-imagine traditional practices and business models, transform technological paradigms, improve public trust, and promote an open and connected world.
“Pathbreaking research takes place in India, resulting in important advances in science around the world,” said Nicholas B. Dirks, President and CEO of The New York Academy of Sciences. “This prize is focused not only on science, but on innovative discoveries that put science to work for the betterment of society, to solving major global challenges in three core areas. We are so pleased to be working with Tata, and Chairman N. Chandrasekaran, to support scientific and technical innovation in India. It will also raise national and international awareness of India’s strengths in scientific research and development.”
The Tata Transformation Prize is the latest in a series of prominent awards and scholarship programs the Academy and its partners present each year to accomplished early-career and established scientists around the world. These initiatives, along with education and professional development programs for students and young scientists, reflect the Academy’s broader commitment to strengthening and diversifying the pipeline for skilled and talented scientists globally.
Founded by Jamsetji Tata in 1868, the Tata Group is a global enterprise, headquartered in India, comprising 30 companies across ten verticals. The group operates in more than 100 countries across six continents, with a mission ‘To improve the quality of life of the communities we serve globally, through long-term stakeholder value creation based on Leadership with Trust’.
Tata Sons is the principal investment holding company and promoter of Tata companies. Sixty-six percent of the equity share capital of Tata Sons is held by philanthropic trusts, which support education, health, livelihood generation and art and culture.
In 2021-22, the revenue of Tata companies, taken together, was US $128 billion (INR 9.6 trillion). These companies collectively employ over 935,000 people.
Each Tata company or enterprise operates independently under the guidance and supervision of its own board of directors. There are 29 publicly-listed Tata enterprises with a combined market capitalisation of $311 billion (INR 23.6 trillion) as on March 31, 2022. Tata Group Companies include Tata Consultancy Services, Tata Motors, Tata Steel, Tata Chemicals, Tata Consumer Products, Titan, Tata Capital, Tata Power, Indian Hotels, Tata Communications, Tata Electronics, Air India and Tata Digital.
Recent progress in the understanding of human disease has led to an explosion in the number of new medicines and therapeutics available for adults — however, significantly fewer drugs are developed and evaluated specifically for children due to complex ethical and logistical issues. Listen to this podcast addressing topics on how to provide children with evidence-based treatments while protecting them from inappropriate research.
This podcast highlights discussions from the Ethical Considerations in Research for Pediatric Populations symposium presented by The New York Academy of Sciences and NYU Grossman School of Medicine and is made available thanks to funding provided by Johnson & Johnson.
Applications for postdoctoral researchers at New York City institutions will be accepted between October 5 and December 9, 2022.
New York, NY | September 29, 2022 — The New York Academy of Sciences and the Leon Levy Foundation announced today that the Academy will be accepting applications from October 5 through December 9, 2022 for the Leon Levy Scholarships in Neuroscience program. The program will support exceptional young researchers across the five boroughs of New York City as they pursue innovative investigations in neuroscience and advance in their careers toward becoming independent principal investigators.
Up to ten Scholars will be selected in the inaugural group, each receiving support for three years beginning September 1, 2023. The Scholars will receive stipends of 125% of the National Institutes of Health minimum salary for postdoctoral fellows.
Women and young scientists from groups historically underrepresented in the sciences are especially encouraged to apply. The program features self-nomination and is designed to broaden the field and to support researchers who might otherwise not have equal opportunity to secure postdoctoral funding.
Supporting Promising, Young Scholars
“Neuroscience has been a field of remarkable progress, and the Leon Levy Foundation has long been a leader in supporting research in this field,” said Shelby White, Founding Trustee of the Leon Levy Foundation. “To continue to make great strides in neuroscience, we need to make sure the most gifted young researchers have every opportunity to advance in their careers. Working with The New York Academy of Sciences, we can support talented postdoctoral scholars, and remove barriers to their success.”
“These Scholarships provide a unique level of autonomy and support for promising young scientists, to promote creativity and collaboration,” said Nicholas B. Dirks, the Academy’s President and CEO. “Working with the Leon Levy Foundation, we will use the Scholars Program to help young people from all backgrounds gain the skills and access to resources they need to succeed in competitive academic research. This will help diversify the community of successful, professional scientists in this field.”
“The Academy has significant experience supporting graduate students, postdoctoral fellows, and early career scientists,” said Amanda Sadacca, PhD, Director of Awards at the Academy. “And we will use our strength in these areas to provide significant additional training and career-building opportunities for Leon Levy Scholars.”
About the Program
The program features structured mentorship by distinguished senior scientists. Elective workshops will help Scholars with grant writing, and in developing leadership, communications, and management skills. The programs will enhance collaboration and partnerships, encourage mentorship and networking, foster data sharing, and advance team science.
“There are often many stresses in a young scientist’s life, and we want to remove as many early-career barriers as we can,” White said. “So in addition to the annual stipend, the scholarships also provide generous supplements for child or family care, an allowance for computer equipment, and other benefits to help ease financial burdens. We know that the strongest possible science will result.”
Applicants must hold a doctoral degree (PhD, DPhil, MD, DDS, DVM, or the equivalent) and possess no more than three years of cumulative postdoctoral experience as of September 1, 2023. Scholars will be funded for research in neuroscience or one of its sub-disciplines, including (but not limited to):
Cellular & Molecular Neuroscience
Systems Neuroscience
Cognitive & Behavioral Neuroscience
Computational Neuroscience
Translational & Clinical Neuroscience
Eligible Institutions
Applicants must be employed by one of the institutions listed below at the time the scholarships begin, and should have the support of their proposed research advisor at the time of application.
Adelphi University
Albert Einstein College of Medicine
Barnard College
City College of New York
CUNY Brooklyn College
CUNY College of Staten Island
CUNY Graduate Center
CUNY Hunter College
CUNY Lehman College
CUNY School of Medicine
CUNY Queens College
Columbia University
Columbia University Irving Medical Center
Cooper Union
Cornell Tech
The Feinstein Institute for Medical Research
Flatiron Institute
Fordham University
Icahn School of Medicine at Mount Sinai
Long Island University
Memorial Sloan Kettering Cancer Center
New York Blood Center
New York University
NYU Langone Health
Pace University
The Rockefeller University
SUNY Downstate Medical Center
Weill Cornell Medicine
The Leon Levy Scholarships in Neuroscience program is the continuation of an earlier fellowship program started by the Foundation in 2009. To date, the Foundation has supported 155 fellows in neuroscience. The new program broadens the list of eligible institutions, and will bring together both new Scholars and past program alumni into one group for networking, collaboration, and the dissemination of scientific research.
For additional information or to become an eligible employing institution, please contact: LeonLevy@nyas.org.
About the Leon Levy Foundation
The Leon Levy Foundation, founded in 2004, is a private, not-for-profit foundation created from Leon Levy’s estate by his wife and Founding Trustee, Shelby White. The Foundation continues Leon Levy’s philanthropic legacy and builds on his vision, supporting the preservation, understanding and expansion of knowledge in the ancient world, Arts and Humanities, Nature and Gardens, Neuroscience, Human Rights, and Jewish Culture. To learn more, visit: leonlevyfoundation.org
Can we stop the pain? It may be the oldest question in medicine, and it remains one of the most important. But with chronic pain afflicting billions of people worldwide, and few effective treatments besides highly addictive opioids, researchers are still searching for better answers.
On May 3-4, the New York Academy of Sciences, in collaboration with Science Translational Medicine, convened the Advances in Pain conference. Across the meeting’s two keynote presentations, nine sessions of talks, and concluding panel discussion, leading experts in many branches of pain research discussed the field’s biggest challenges and latest developments.
Highlights
Specific ion channels on neurons, such as Nav1.7, are critical components of pain sensing and potential drug targets for new analgesics.
Several novel laboratory models are revealing new details of nociception, or pain sensing.
Large databases of genetic and clinical records are helping researchers link specific genes with common pain conditions.
Neuroimaging and sleep studies may offer objective ways to measure the severity of chronic pain.
New mechanistic data are pointing researchers toward novel strategies for analgesic drug development.
A subset of gut epithelial cells is critical for sensing visceral pain.
The immune system links tightly to pain sensation, through multiple mechanisms scientists are now beginning to uncover.
Data mining reveals subsets of neurons with distinct responses to nerve injury, including chronic pain.
Understanding sex and ethnic differences in pain perception requires new strategies in experimental design and data analysis.
Besides neurons, Schwann cells can also carry pain signals.
Novel drug discovery platforms and trial designs can accelerate the development of new analgesics.
Part 1
Speakers
David Bennett, MB, PhD Oxford University, Nuffield Department of Clinical Neurosciences
Sarah E. Ross, PhD University of Pittsburgh
Jing Wang, MD, PhD NYU Langone Health
Tuning into the pain channel
A life free of pain may sound ideal, but as David Bennett explained in the meeting’s opening keynote presentation, individuals with defects in pain sensing often suffer tremendous difficulties. Describing one 26-year-old man with such a condition, Bennett explained that “he had pretty much fractured every long bone in his body, he is stunted because he’s destroyed all the growth plates … and had severe burns and mouth injuries.” The patient’s sister, who had the same condition, died of undiagnosed sepsis.
Genetic analysis revealed that the patient had a rare set of loss-of-function mutations in the gene for Nav1.7, a sodium ion channel expressed in nociceptors, or pain sensing neurons. Using a sophisticated cell culture system that mimics pain signaling through nociceptors, Bennett and his colleagues have characterized Nav1.7 in detail, and determined that it acts early in the pain signaling process, amplifying the electrical signal in the nociceptors to ensure that it’s relayed to the central nervous system.
Patients with gain-of-function mutations that make Nav1.7 overactive have the opposite problem: incurable chronic pain. Bennett’s team studied the Nav1.7 mutations in these patients, and discovered that the degree of the biochemical defect in a patient’s channel proteins correlates directly with the time of onset of their pain condition.
Based on his findings in patients with these rare, extreme pain disorders, Bennett hypothesized that Nav1.7 could also drive more common conditions. As rates of diabetes skyrocket globally, millions of people are developing diabetic neuropathy, which causes chronic pain only in a subset of patients. In an effort to determine what distinguishes painful from pain-free diabetic neuropathy, Bennett’s team looked at Nav1.7 gene sequences for patients with the condition.
“The rare variants in Nav1.7 seemed to cluster much more in the painful versus the painless diabetic neuropathy groups, so this is now acting as a risk factor, in the sense that these people did not experience [chronic] pain prior to developing diabetes,” Bennett says.
Some variants of Nav1.7 apparently predispose people to develop chronic pain, but the condition doesn’t manifest itself until a second event, such as diabetes, triggers it. A closer look at clinical testing results in these patients revealed that those with the rare variants were also more sensitive to certain stimuli, such as burning pain and pressure pain.
Nav1.7 isn’t the only ion channel involved in pain, though. The researchers have also identified strong associations between pain disorders and mutations in the related channel proteins Nav1.8 and Nav1.9, highlighting the diversity of channelopathies that can derail pain sensing. Indeed, an analysis of data from the UK Biobank, which has whole genome sequences and medical records for 100,000 Britons, revealed that voltage-gated sodium channels were the largest group of variants associated with neuropathic pain.
Based on his findings, Bennett advocates using both clinical testing data and gene sequencing to stratify patients according to which treatments are most likely to work for them. In particular, sodium channel blocking drugs appear to work much better in patients with variant channels predisposing them to pain.
Where does it hurt?
The meeting’s first regular session focused on efforts to dissect the central pain circuits in the nervous system. For Sarah Ross, the dissection is literal: she carefully removes a piece of a mouse spinal cord, along with the sensory nerves connected to a patch of skin from the animal’s hind paw, keeping all of the neuronal connections intact. Using luminescent probes, her team can then watch the activation of specific neurons in response to stimuli.
“We can see some neurons respond to heat, other neurons will respond to cool, other neurons will respond to mechanical stimuli,” said Ross.
Many neurons also respond to multiple stimuli, and mapping these responses reveals that distinct classes of neurons function as amplifiers, tuners, and integrators of pain signals.
Jing Wang studies what happens to pain signals in the cerebral cortex of the brain. Using optogenetics, which allows him to stimulate specific neurons in the brains of mice with light, he has identified subsets of neurons in the anterior cingulate cortex and prefrontal cortex that respond to pain.
In mice with experimentally induced chronic pain, low-intensity stimulation of the prefrontal cortex restores normal pain control. Wang’s lab is now studying ways to achieve similar responses with less invasive methods, including the drug ketamine and brain-machine interfaces.
“The cortex processes and regulates pain, but its normal endogenous function can be impaired by chronic pain, and [restoring cortical regulation] has the potential to transform pain treatment,” said Wang.
Part 2
Speakers
Aarno Palotie, MD, PhD Institute for Molecular Medicine, Finland
Luda Diatchenko, MD, PhD McGill University
Irene Tracey, MA (Oxon), DPhil, FRCA, FMedSci University of Oxford
Alban Latremoliere, MSc, PhD Johns Hopkins University
The pains of the father
Aarno Palotie began the meeting’s session on the genetics of pain by discussing his results from large-scale studies on migraine. With the exception of some rare, strictly inherited forms of the condition, these sporadic, debilitating headaches usually stem from variations in numerous common genes. To identify those genes, Palotie and a large team of collaborators scrutinized genetic and medical data from hundreds of thousands of migraine sufferers.
The effort revealed over 100 gene loci linked to migraine, mostly in regulatory regions associated with genes expressed in cardiovascular tissue and the central nervous system. Tracking those variants in another large data set revealed a cumulative effect.
“We can see that those with a high polygenic risk score, meaning a high load of common variants, they seem to have an earlier onset of migraine,” said Palotie.
Using data from the 500,000 participants in the UK Biobank, Luda Diatchenko and her colleagues have performed a similar analysis to identify genetic variants linked to chronic pain. The investigators subdivided chronic pain patients based on the type of pain they experienced, such as back pain, hip pain, knee pain, and multi-site pain.
Analyzing gene sequences for these sub-groups showed that multi-site pain had the highest correlation with specific gene variants. The gene most strongly linked to multi-site pain encodes a receptor protein involved in guiding nerve axons in development.
“This is one example of how [genome-wide association studies] can show us a new mechanism which contributes to human chronic pain conditions,” said Diatchenko.
On a scale of one to ten
The meeting’s third session focused on one of the biggest challenges in studying pain: measuring it. Clinical studies attempt to quantify pain severity with patient questionnaires, while animal experiments rely on behavioral responses, but both methods are notoriously unreliable.
Ilene Tracey hopes to solve that problem with neuroimaging, linking specific patterns of neuronal activation to painful stimuli.
“We’ve got now quite a good array of tools that are reasonably well developed and robust, that allow you to look at … ways that patients will experience their pain,” said Tracey.
By combining functional magnetic resonance imaging with electroencephalography, video analysis, and other sensing methods, this approach could allow researchers to quantify patient responses to pain treatment more reliably than current, fundamentally qualitative methods. Using machine learning, Tracey’s team can now measure pain and also distinguish different categories of it, such as physical versus emotional pain.
Sleep disturbances might also provide a pain gauge.
“The vast majority of patients with chronic pain suffer from poor sleep quality,” said Alban Latremoliere, who has been studying this connection as a potential pain biomarker.
By tracking electroencephalography and other measurements in sleeping mice, he and his colleagues have found that nerve injury, which causes chronic neuropathic pain, also changes the animals’ sleep architecture. Compared to uninjured animals, those with injured nerves suffer multiple brief interruptions in the non-REM phase of their sleep. When the injury heals, the normal sleep architecture returns; Latremoliere now hopes to use these patterns to quantify neuropathic pain severity and treatment efficacy in humans.
Part 3
Speakers
Greg Scherrer, PhD University of North Carolina
Venetia Zachariou, PhD, MBBS, MMed, MS Icahn School of Medicine at Mount Sinai
Rajesh Khanna, PhD New York University
David J. Julius, PhD University of California, San Francisco (UCSF)
The hurt blocker
As Greg Scherrer pointed out in the meeting’s fourth session, the real problem with pain isn’t that it exists, but that it’s unpleasant.
“If we were to understand how our brain collects this information from sensory neurons and the spinal cord to make pain unpleasant … maybe we’ll discover new ways to treat pain,” said Scherrer.
Indeed, a patient whose basolateral amygdala was removed to treat epilepsy could still sense painful stimuli, but didn’t label them as painful; the unpleasantness was gone. Examining mice with various alterations to the same brain region, Scherrer and his colleagues believe they have identified the amygdala cells responsible for connecting pain to unpleasantness. The investigators are now trying to identify receptors on those cells that would be good drug targets for new pain treatments.
Venetia Zachariou is also dissecting cellular signaling pathways to target in pain treatment, and her lab has uncovered several promising leads in recent years. When the COVID-19 pandemic derailed that work, though, the scientists quickly pivoted to apply their skills and techniques to study the new disease’s neuronal pathogenesis.
In a hamster model, they found that SARS-CoV-2, the virus that causes COVID-19, can acutely infect nerves in the dorsal root ganglia, which are also involved in pain sensing. Looking more closely at both the hamster model and a mouse model of SARS-CoV-2 infection, Zachariou has identified distinct changes in neurons’ gene expression patterns after virus infection, including a signature similar to that seen in models of neuropathic pain.
One of the most popular targets for researchers trying to develop new pain therapies is the sodium channel Nav1.7, a “pain amplifier” that several speakers at the meeting discussed. Rajesh Khanna is also interested in Nav1.7, but instead of targeting the protein directly, his team is trying to identify proteins that interact with it. That work led them to focus on collapsin response mediator protein 2 (Crmp2), which regulates Nav1.7 signaling.
Mice lacking Crmp2 are resistant to chronic pain, suggesting that drugs inhibiting its action would be good pain therapy candidates. After conducting extensive mechanistic studies, Khanna started a company to identify such inhibitors. So far, the company has optimized a lead compound that appears to stop chronic pain in animal models, without causing detectable side effects or tolerance.
You feel it in your gut
The meeting’s first day concluded with a keynote presentation by David Julius, who discussed his work on chronic visceral pain. This subtype of chronic pain, which can be caused by gut infection or non-infectious conditions such as inflammatory bowel disease, affects about 15% of the population. It’s three times more common in women than men, but nobody knows why.
“We’re interested in a particular aspect of visceral pain signaling, and that involves the interaction of sensory nerve fibers with the gut epithelium,” said Julius.
A subset of gut epithelial cells, called enterochromaffin cells, plays an outsize role in that interaction. Comprising only a fraction of a percentage of all gut epithelial cells, enterochromaffin cells make about 90% of the body’s serotonin, a potent neurotransmitter protein. They also fire electrical signals that could propagate to nearby neurons.
Julius wanted to analyze that process in live mice, but wasn’t happy with the standard mouse system for those types of experiments. That model involves putting irritants into a mouse’s gut to trigger a major inflammatory response, after which the animal remains hypersensitive to physical stimuli such as colon distention.
“Do we need to … put the mouse through all that, or can you have a model that’s simpler [and] does not require all the sequellae of an inflammatory episode?” asked Julius.
Instead, he and his colleagues first tried studying enterochromaffin cells in the context of cultured enteroids, pieces of intestinal epithelium that can mimic many aspects of gut biology in a petri dish. That system revealed that enterochromaffin cells respond to numerous compounds that fall into three general classes: ingested irritants, metabolites of common gut microbes, and endogenous regulatory hormones.
“So, we want to know how these cells integrate all this information, and what role this plays in maladaptive situations like [inflammatory bowel disease],” said Julius.
Based on those results, the researchers moved to a more complex system, an explanted piece of a mouse colon with its connecting nerves. Monitoring the electrical signals in the connected nerves reveals sensory signals from the explanted gut. In this setup, bathing the colon section with isovalerate, a bacterial metabolite that triggered a response from enterochromaffin cells in the enteroid experiment, makes it hypersensitive to subsequent physical or biochemical stimuli. This system also revealed different response patterns in guts from male and female mice.
Having demonstrated that isovalerate could induce gut hypersensitivity without the inflammatory response of harsher irritants, Julius’s team next tried looking at its effect in live mice. They used a small balloon in the colon, similar to an endoscope, as a stimulus, and monitored abdominal muscle contraction, a behavioral response to pain. Treating the mice with isovalerate increased the magnitude of subsequent pain responses potently in male mice, but less so in females, consistent with the explant results.
Subsequent experiments showed that enterochromaffin cells mediate these responses in live mice, apparently through both serotonin secretion and direct electrical signaling to neurons, and that these cells seem to respond differently in male and female mice.
Part 4
Speakers
Isaac Chiu, PhD Harvard Medical School
Camila Svensson, MS, PhD Karolinska Institutet
Alexander J. Davies, PhD Nuffield Department of Clinical Neurosciences
Dana Orange, MD Rockefeller University
Shrinivasan Raghuraman, PhD University of Utah
Jeffrey S. Mogil, PhD McGill University
Frank Porreca, PhD University of Arizona
Roger Fillingim, PhD University of Florida
Is antibody hurt?
Infections commonly cause pain, which researchers had long assumed was just a byproduct of the body’s inflammatory response. However, as Isaac Chiu explained in the meeting’s session on neuroimmune and autoimmune mechanisms in pain, infecting pathogens can also interact directly with nociceptors, or pain-sensing neurons. In one set of mouse experiments, for example, Chiu’s team found that nociceptors in the intestine can detect infection with Salmonella enterica, triggering a response that decreases the number of M cells, the specialized intestinal epithelial cells S. enterica preferentially infects.
“These neurons actually regulate cell numbers, [which] not only shuts down the number of gates for pathogen entry, it also helps a protective microbe … attach better on the surface of the epithelium,” said Chiu.
Camila Svensson discussed a pain condition that has baffled researchers and clinicians for decades: fibromyalgia. Characterized by pain hypersensitivity in soft tissues, sometimes coupled with neuropathic pain, the condition has long eluded efforts to uncover its etiology and underlying mechanisms.
After serendipitously discovering evidence for autoantibodies in fibromyalgia patients, Svensson has now developed human tissue and mouse models to characterize these antibodies in more detail. Transferring antibodies from fibromyalgia patients into mice causes pain hypersensitivity in the animals, and patients with higher levels of antibodies that react with human dorsal root ganglia cells have more severe disease.
“This suggests that there is an autoimmunity in subpopulations of fibromyalgia patients,” said Svensson, adding that besides suggesting a mechanism for the disease, autoantibody levels could help stratify patients in clinical trials.
The body’s own immune response is also a key contributor to chronic neuropathic pain, especially through neuroinflammation. Alexander Davies presented his work on another component of neuropathic pain: the cytotoxic cellular response.
Cytotoxic cells normally detect cancerous or virally-infected cells and target them for destruction, but they can also target injured neurons. Dissecting this response in an extensive series of experiments in mice, Davies and his colleagues have found that a specific receptor on cytotoxic cells allows them to target nociceptors after nerve injury, leading to degeneration of the damaged axons and resolution of pain hypersensitivity.
“So, our data suggest that intact sensory networks are a source of ongoing neuropathic hypersensitivity, and that by targeting those, we can help to resolve that,” said Davies.
Short, sharp shocks
Dana Orange gave the first of two short “data blitz” presentations, providing an overview of her group’s work on rheumatoid arthritis pain. Though inflammation of joints is a hallmark of this form of arthritis, Orange noticed an odd discrepancy.
“Patients who really don’t have a lot of inflammation were reporting a lot of pain,” she said.
Through a combination of human gene expression and mouse studies, she’s found that nerve development may play a bigger role than inflammation in driving rheumatoid arthritis pain.
Shrinivasan Raghuraman described his approach to characterizing chronic pain mechanisms, using a rat model. By collecting thousands of data points from individual rat neurons under different conditions, his lab has identified 19 different subsets of neurons with distinct responses to nerve injury. Raghuraman hopes that correlating the cells’ electrical responses with their gene transcription profiles will identify the underlying mechanisms driving chronic pain, and how different candidate drugs can influence it.
Sex and race
In the session on sex and ethnic differences in pain, Jeffrey Mogil began by pointing out a critical flaw in traditional pain research methods. Despite ample evidence that women experience more pain than men, “80 percent of preclinical studies use male rats or male mice only,” said Mogil.
That skew overlooks important differences in the biology of pain in males and females, though. In a mouse model of chronic neuropathic pain, for example, Mogil’s lab has linked chronic pain to premature shortening of chromosome ends, or telomeres – but only in male mice. Besides studying both sexes instead of just one, Mogil argued that researchers need to extend their animal studies to monitor chronic pain for longer time periods, to account for age-related phenomena such as telomere shortening.
Frank Porreca also looks at sex differences in pain, but focuses on the role of stress. Clinical data clearly show that stress exacerbates functional pain syndromes such as inflammatory bowel disease, migraine, and fibromyalgia, all of which are more prevalent in women than men.
To study such syndromes, Porreca’s team developed a mouse model in which they restrain the animals for a short time to induce stress, then treat them with a compound that causes headaches. These stress-primed mice develop allodynia, interpreting normally non-painful stimuli as painful, while controls that only got the headache-inducing compound didn’t.
While both male and female mice exhibited the same response, Porreca found that it operates through different biochemical mechanisms in the two sexes, underscoring the importance of studying both in preclinical research.
Unlike sex, race and ethnicity lack clear biological definitions.
“It’s important to keep in mind that race and ethnicity are not causal factors, but rather proxies for these many psychosocial and biopsychosocial factors, largely driven by systemic societal and environmental exposures,” said Roger Fillingim.
At the same time, the groups that suffer disproportionately from racial and ethnic health disparities are often the least-studied. That’s certainly the case in pain research and treatment. Indeed, experiments suggest that Black patients may experience more pain than white ones, but health data show they’re less likely to be treated for pain in hospitals and clinics.
Summarizing a large body of additional evidence for similar skews in various minoritized groups, Fillingim advocated more holistic approaches to pain research across and within sub-populations.
Part 5
Speakers
Alexander Chesler, PhD National Center for Complementary and Integrative Health (NCCIH), NIH
Patrik Ernfors, PhD Karolinska Institutet
Clifford Woolf, MD, PhD Harvard Medical School
Bryan Roth, MD, PhD University of North Carolina
Kelly Knopp, PhD Eli Lilly
Get the sensation
The meeting’s penultimate session focused on how sensory signals such as pain propagate toward the central nervous system. Alexander Chesler started the session with a discussion of his work on peripheral sensory neurons.
To study these cells, Chesler and his colleagues initially developed an elegant system that allowed them to probe the responses of individual mouse cells in the trigenimal ganglion, a nerve cluster that receives sensory signals. That revealed a specific subset of neurons that responded only to a painful stimulus, while other subsets responded to gentle touches. By extending the system with gene expression profiling, and correlating responses in the mouse with those in a human patient who lacks a receptor critical for mechanical sensation, the scientists are now tracing pain-sensing pathways in unprecedented detail.
Neurons aren’t the only cells carrying pain signals, though, as Patrik Ernfors has discovered. In tracing sensory circuits, he and his colleagues discovered that Schwann cells, support cells closely associated with peripheral neurons, are also stem cells that form a sensory organ under the skin.
Using genetically modified mouse models that allowed them to selectively activate these Schwann cells, Ernfors and his colleagues discovered that both the Schwann cells and their associated neurons can initiate acute pain sensations. Further work revealed that the Schwann cells also appear to become sensitized during the development of arthritis.
“We believe that we have found the mechanosensory skin organ that is associated with [mechanical pain sensation],” said Ernfors, adding that these cells could contribute to allodynia in arthritis.
Something for the pain
Clifford Woolf began the meeting’s final session, on finding new ways to treat pain, with a summary of his team’s novel approach to drug discovery. Currently, most pharmaceutical companies focus on finding compounds that can target specific cellular molecules known to be involved in pain, then trying to develop them into drugs.
In 2010, Woolf advocated an alternative strategy, screening drugs to find those that inhibit stem cell-derived pain-sensing neurons, without worrying about their mechanisms of action.
“However, the question was how to execute on this,” he said.
After extensive effort, his team can now derive the correct neuron types from patients’ cells. Screening libraries of compounds against these cells has yielded several promising hits, which inhibit pain signaling in nociceptors without affecting other cell types.
Others hope to broaden the scope of target-based drug screening, which has focused on a large and diverse class of cell surface proteins called G-protein coupled receptors, or GPCRs.
“But … when we mapped the drugs onto the phylogeny of all the [GPCRs] in the genome, only a few targets actually came out as being targets of approved drugs,” said Bryan Roth, adding that “there are many, many other potential targets for treating pain and other serious conditions.”
To test those targets, Roth’s team developed an assay that allows them to test drugs against a library encompassing 90% of GPCRs encoded in the human genome. That has revealed several new targets, which the researchers are now testing with more specific screens, ultimately hoping to develop safer opioids.
Kelly Knopp began the meeting’s final talk with the grim statistics of chronic pain: affecting about one fourth of the global population, the direct and indirect costs of this condition add up to more than a trillion dollars.
“[Meanwhile,] the probability of technical success for pain [drugs] is worse than any other therapeutic area,” said Knopp.
To address that, she and her colleagues have focused on establishing standardized protocols for phase 2 proof-of-concept trials of pain treatments. Their approach uses sophisticated statistical techniques and uniform trial designs to enable testing of many more drug candidates, without exceeding available funding and medical trial capacity.
After the presentations, a panel of speakers from the meeting discussed several of the field’s biggest challenges. Chief among them are the immense burden of opioid addiction, and the difficulty of shifting real-world clinical treatment toward less addictive but possibly less effective therapies for chronic pain. Despite the difficulties, many researchers in the field remain optimistic.
As Ilene Tracey said in her presentation, “We’re often quite doom and gloom in the pain field, [but] we’ve actually got a lot of different tools at our disposal, [and] we should be more confident about where the field has got to and where it can go quite rapidly.”
The Blavatnik Awards for Young Scientists in the United Kingdom are the largest unrestricted prize available to early career scientists in the Life Sciences, Physical Sciences & Engineering, and Chemistry in the UK. The three 2021 Laureates each received £100,000, and two Finalists in each category received £30,000 per person. The honorees are recognized for their research, which pushes the boundaries of our current technology and understanding of the world. In this event, held at the historic Banqueting House in London, the UK Laureates and Finalists had a chance to explain their work and its ramifications to the public.
Victoria Gill, a Science and Environment Correspondent for the BBC, introduced and moderated the event. She noted that “Science has saved the world and will continue to do so,” and stressed how important it is for scientists to engage the public and share their discoveries at events like this. This theme arose over and over again over the course of the day.
Symposium Highlights
Single-cell analyses can reveal how multicellular animals develop and how our immune systems deal with different pathogens we encounter over the course of our lives.
Viruses that attack bacteria—bacteriophages—may help us fight antibiotic resistant bacterial pathogens.
Fossils offer us a glimpse into what life on Earth was like for the millennia in which it thrived before mammals took over.
Stacking layers of single-atom-thick sheets can make new materials with desired, customizable properties.
Memristors are electronic components that can remember a variety of memory states, and can be used to build quicker and more versatile computer chips than currently used.
The detection of the Higgs boson, which had been posited for decades by mathematical theory but was very difficult to detect, confirmed the Standard Model of Physics.
Single molecule magnets can be utilized for high density data storage—if they can retain their magnetism at high enough temperatures.
When examining how life first arose on Earth, we must consider all of its requisite components and reactions in aggregate rather than assigning primacy to any one of them.
Speakers
Stephen L. Brusatte The University of Edinburgh
Sinéad Farrington The University of Edinburgh
John Marioni European Bioinformatics Institute and University of Cambridge
David P. Mills The University of Manchester
Artem Mishchenko The University of Manchester
Matthew Powner University College London
Themis Prodromakis University of Southampton
Edze Westra University of Exeter
Innovating in Life Sciences
Speakers
John Marioni, PhD European Bioinformatics Institute and University of Cambridge, 2021 Blavatnik Awards UK Life Sciences Finalist
Edze Westra, PhD University of Exeter, 2021 Blavatnik Awards UK Life Sciences Finalist
Stephen Brusatte, PhD The University of Edinburgh, 2021 Blavatnik Awards UK Life Sciences Laureate
How to Build an Animal
John Marioni, PhD, European Bioinformatics Institute and University of Cambridge, 2021 Blavatnik Awards UK Life Sciences Finalist
Animals grow from one single cell: a fertilized egg. During development, that cell splits into two, and then into four, and so on, creating an embryo that grows into the billions of cells comprising a whole animal. Along the way, the cells must differentiate into all of the different cell types necessary to create every aspect of that animal.
Each cell follows its own path to arrive at its eventual fate. Traditionally, the decisions each cell has to make along that path have been studied using large groups of cells or tissues; this is because scientific lab techniques have typically required a substantial amount of starting material to perform analyses. But now, thanks in large part to the discoveries of John Marioni and his lab group, we have the technology to track individual cells as they mature into different cell types.
Marioni has created analytical methods capable of observing patterns in all of the genes expressed by individual cells. Importantly, these computational and statistical methods can be used to analyze the enormous amounts of data generated from the gene expression patterns of many individual cells simultaneously. In addition to furthering our understanding of cell fate decisions in embryonic development, this area of research—single cell genomics—can also be applied to many other processes in the body.
One relevant application is to the immune system: single cell genomics can detect immune cell types that are activated by exposure to a particular pathogen. To illustrate this, Marioni showed many gorgeous, colorized images of individual cells, highlighting their unique morphology and function. Included in these images was histology showing profiles of different types of T cells elicited by infection with SARS-CoV-2 (the virus that causes COVID-19).
The cells were computationally grouped by genetic profile and graphed to show how the different cell types correlated with disease severity. There are many other clinical applications of his research into genomics. For instance, he said, if we know exactly which cell types in the body express the targets of specific drugs, we will be better able to predict that drug’s effects (and side effects).
In addition to his lab work, Marioni is involved in the Human Cell Atlas initiative, a global collaborative project whose goal it is to genetically map all of the cell types in healthy human adults. When a cell uses a particular gene, it is said to “transcribe” that gene to make a particular protein—thus, the catalog of all of the genes one cell uses is called its “transcriptome.” The Human Cell Atlas is using these single cell transcriptomes to create the whole genetic map.
This research is currently completely redefining how we think of cell types by transforming our definition of a “cell” from the way it looks to the genetic profile.
Bacteria and Their Viruses: A Microbial Arms Race
Edze Westra, PhD University of Exeter, 2021 Blavatnik Awards UK Life Sciences Finalist
All organisms have viruses that target them for infection; bacteria are no exception. The viruses that infect bacteria are called bacteriophages, or phages.
Edze Westra’s lab studies how bacteria evolve to defend themselves against infection by phage and, specifically, how elements of their environment drive the evolution of their immune systems. Like humans, bacteria have two main types of immune systems: an innate immune system and an adaptive immune system. The innate immune system works similarly in both bacteria and humans by modifying molecules on the cell surface so that the phage can’t gain entry to the cell.
In humans, the adaptive immune system is what creates antibodies. In bacteria, the adaptive immune system works a little bit differently—a gene editing system, called CRISPR-Cas, cuts out pieces of the phage’s genome and uses it as a template to identify all other phages of the same type. Using this method, the bacterial cell can quickly discover and neutralize any infectious phage by destroying the phage’s genetic material. In recent years, scientists have harnessed the CRISPR-Cas system for use in gene editing technology.
Westra wanted to know under what conditions do bacteria use their innate immune system versus their adaptive immune system: How do they decide?
In studies using the bacterial pathogen Pseudomonas aeruginosa, his lab found that the decision to use adaptive vs. innate immunity is controlled almost exclusively by nutrient levels in the surrounding environment. When nutrient levels are low, the bacteria use the adaptive immune system, CRISPR-Cas; when nutrient levels are high, the bacteria rely on their innate immune system. He recognized that this means we can artificially guide the evolution of bacterial defense by controlling elements in their environment.
When we need to attack pathogenic bacteria for medical purposes, such as in a sick or infected patient, we turn to antibiotics. However, many strains of bacteria have developed resistance to antibiotics, leaving humans vulnerable to infection.
Additionally, our antibiotics tend to kill broad classes of microbes, often damaging the beneficial species we harbor in our bodies along with the pathogenic ones we are trying to eliminate. Phage therapy—a medical treatment where phages are administered to a patient with a severe bacterial infection—might be a good way to circumvent antibiotic resistance while also attacking bacteria in a more targeted manner, harming only those that harm us and leaving the others be.
Although it is difficult to manipulate bacterial nutrients within the context of a patient’s body, we can use antibiotics to direct this behavior. Antibiotics that are shown to limit bacterial growth will induce the bacteria to use the CRISPR-Cas strategy, mimicking the effects of a low-nutrient environment; antibiotics that work by killing bacteria will induce them to use their innate defenses. In this way, it may be possible to direct the evolution of bacterial defense systems in order to reveal their weaknesses and target them with phage therapy.
The Rise and Fall of the Dinosaurs
Stephen Brusatte, PhD The University of Edinburgh, 2021 Blavatnik Awards UK Life Sciences Laureate|
Stephen Brusatte is a paleontologist, “and paleontologists”, he says, “are really historians”. Just as historians study recorded history to learn about the past, paleontologists study prehistory for the same reasons.
The Earth is four and a half billion years old, and humans have only been around for the last three hundred and fifty thousand of those years. Dinosaurs were the largest living creatures to ever walk the earth; they started out around the size of house cats, and over eighty million years they evolved into the giant T. rexes, Stegosauruses, and Brontosauruses in our picture books.
They reigned until a six-mile-wide asteroid struck the Earth sixty-six million years ago at the end of the Cretaceous period, extinguishing them along with seventy-five percent of the other species on the planet. Brusatte called this day “the worst day in Earth’s history.” However, the demise of dinosaurs paved the way for mammals to take over.
Fossils can tell us a lot about how life on this planet used to be, how the earth and its occupants respond to climate and environmental changes, and how evolution works over long timescales. Particularly, fossils show how entirely new species and body plans emerge.
Each fossil can yield new knowledge and new discoveries about a lost world, he said. It can teach us how bodies change and, ultimately, how evolution works. It is from fossils that we know that today’s birds evolved from dinosaurs.
Life Sciences Panel Discussion
Victoria Gill started the life sciences panel discussion by asking all three of the awardees if, and how, the COVID-19 pandemic changed their professional lives: did it alter their scientific approach or were they asking different questions?
Westra replied that the lab shutdown forced different, non-experimental approaches, notably bioinformatics on old sequence data. He said that they found mobile genetic elements, and the models of how they moved through a population reminded him of epidemiological models of COVID spread.
Marioni shared that he was inspired by how the international scientific community came together to solve the problem posed by the pandemic. Everyone shared samples and worked as a team, instead of working in isolation as they usually do. Brusatte agreed that enhanced collaboration accelerated discoveries and should be maintained.
Questions from the audience, both in person and online, covered a similarly broad of a range of topics. An audience member asked about where new cell types come from; Marioni explained that if we computationally look at gene transcription changes in single cells over time, we can make phylogenetic trees showing how cells with different expression patterns arise.
A digital attendee asked Brusatte why birds survived the asteroid impact when other dinosaurs didn’t. Brusatte replied that the answer is not clear, but it is probably due to a number of factors: they have beaks so they can eat seeds, they can fly, and they grow fast. Plus, he said, most birds actually did not survive beyond the asteroid impact.
Another audience member asked Brusatte if the theory that the asteroid killed the dinosaurs was widely accepted. He replied that it is widely accepted that the impact ended the Cretaceous period, but some scientists still argue that other factors, like volcanic eruptions in India, were the prime mover behind the dinosaurs’ demise.
Another viewer asked Westra why the environment impacts a bacterium’s immune strategy. He answered that in the presence of antibiotics that slow growth, infection and metabolism are likewise slowed so the bacteria simply have more time to respond. He added that the level of diversity in the attacking phage may also play a role, as innate immunity is better able to deal with multiple variants.
To wrap up the session, Victoria Gill asked about the importance of diversity and representation and wondered how to make awards programs like this more inclusive. All three scientists agreed that it is hugely important, that the lack of diversity is a problem across all fields of research, that all voices must be heard, and that the only way to change it is by having hard metrics to rank universities and departments on the demographics of their faculty.
Innovating in Physical Sciences & Engineering
Speakers
Artem Mishchenko, PhD The University of Manchester, 2021 Blavatnik Awards UK Physical Sciences & Engineering Finalist
Themis Prodromakis, PhD University of Southampton, 2021 Blavatnik Awards UK Physical Sciences & Engineering Finalist
Sinead Farrington, PhD The University of Edinburgh, 2021 Blavatnik Awards UK Physical Sciences & Engineering Laureate
Programmable van der Waals Materials
Artem Mishchenko, PhD The University of Manchester, 2021 Blavatnik Awards UK Physical Sciences & Engineering Finalist
Materials science is vital because materials define what we can do, and thus define us. That’s why the different eras in prehistory are named for the materials used: the Stone Age, the Bronze Age, the Iron Age, the Copper Age. The properties of the materials available dictated the technologies that could be developed then, and the properties of the materials available still dictate the technologies that can be developed now.
Van der Waals materials are materials that are only one or a few atoms thick. The most well-known is probably graphene, which was discovered in 2004 and is made of carbon. But now hundreds of these two-dimensional materials are available, representing almost the whole periodic table, and each has different properties. They are the cutting edge of materials innovation.
Mishchenko studies how van der Waals materials can be made and manipulated into materials with customizable, programmable properties. He does this by stacking the materials and rotating the layers relative to each other. Rotating the layers used to be painstaking, time-consuming work, requiring a new rig to make each new angle of rotation. But his lab developed a single device that can twist the layers by any amount he wants. He can thus much more easily make and assess the properties of each different material generated when he rotates a layer by a given angle, since he can then just reset his device to turn the layer more or less to devise a new material. Every degree of rotation confers new properties.
His lab has found that rotating the layers can tune the conductivity of the materials and that the right combination of angle and current can make a transistor that can generate radio waves suitable for high frequency telecommunications. With infinite combinations of layers available to make new materials, this new field of “twistronics” may generate an entirely new physics, with quantum properties and exciting possibilities for biomedicine and sustainability.
Memristive Technologies: From Nano Devices to AI on a Chip
Themis Prodromakis, PhD University of Southampton, 2021 Blavatnik Awards UK Physical Sciences & Engineering Finalist
Transistors are key elements in our electronic devices. They process and store information by switching between on and off states. Traditionally, in order to increase the speed and efficiency of a device one increased the number of transistors it contained. This usually entailed making them smaller. Smartphones contain seven billion transistors! But now it has become more and more difficult to further shrink the size of transistors.
Themis Prodromakis and his team have been instrumental in developing a new electronic component: the memristor, or memory resistor. Memristors are a new kind of switch; they can store hundreds of memory states, beyond on and off states, on a single, nanometer-scale device. Sending a voltage pulse across a device allows to tune the resistance of the memristor at distinct levels, and the device remembers them all.
One benefit of memristors is that they allow for more computational capacity while using much less energy from conventional circuit components. Systems made out of memristors allow us to embed intelligence everywhere by processing and storing big data locally, rather than in the cloud. And by removing the need to share data with the cloud, electronic devices made out of memristors can remain secure and private. Prodromakis has not only developed and tested memristors, he is also quite invested in realizing their practical applications and bringing them to market.
Another amazing application of memristors is linking neural networks to artificial ones. Prodromakis and his team have already successfully connected biological and artificial neurons together and enabled them to communicate over the internet using memristors as synapses. He speculates that such neuroprosthetic devices might one day be used to fix or even augment human capabilities, for example by replacing dysfunctional regions of the brain in Alzheimer’s patients. And if memristors can be embedded in a human body, they can be embedded in other environments previously inaccessible to electronics as well.
What Do We Know About the Higgs Boson?
Sinead Farrington, PhD The University of Edinburgh, 2021 Blavatnik Awards UK Physical Sciences & Engineering Laureate
In the Standard Model of particle physics, the bedrock of modern physics, fermions are the elementary particles comprising all of the stable matter in the universe, while bosons—the other collection of elementary particles—are the ones that transmit forces. The Higgs boson, whose existence was theoretically proposed in 1964, is a unique particle; it gives mass to the other particles by coupling with them.
Sinéad Farrington led the group at CERN that further elucidated the properties of the Higgs boson and thus bolstered the Standard Model. The Standard Model “effectively encapsulates a remarkably small set of particles that make up everything we know about and are able to create,” explained Farrington.
“The Higgs boson is needed to maintain the compelling self-consistency of the Standard Model. It was there in theory, but the experimental observation of it was a really big deal. Nature did not have to work out that way,” Farrington said.
Farrington and her 100-person international team at the Large Hadron Collider demonstrated that the Higgs boson spontaneously decays into two fermions called tau leptons. This was experimentally challenging because tau is unstable, so the group had to infer that it was there based on its own degradation products. She then went on to develop the analytical tools needed to further record and interpret the tau lepton data and was the first to use machine learning to trigger, record, and analyze the massive amounts of data generated by experiments at the LHC.
Now she is looking to discover other long-lived but as yet unknown particles beyond the Standard Model that also decay into tau leptons, and plans to make more measurements using the Large Hadron Collider to further confirm that the Higgs boson behaves the way the Standard Model posits it will.
In addition to the satisfaction of verifying that a particle predicted by mathematical theorists actually does exist, Farrington said that another consequence of knowing about the Higgs boson is that it may shed light on dark matter and dark energy, which are not part of the Standard Model. Perhaps the Higgs boson gives mass to dark matter as well.
Physical Sciences & Engineering Panel Discussion
Victoria Gill started this session by asking the participants what they plan to do next. Farrington said that she would love to get more precise determinations on known processes, reducing the error bars upon them. And she will also embark on an open search for new long-lived particles—i.e. those that don’t decay rapidly—beyond the Standard Model.
Prodromakis wants to expand the possibilities of memristive devices, since they can be deployed anywhere and don’t need a lot of power. He envisions machine-machine interactions like those already in play in the Internet of Things as well as machine-human interactions. He knows he must grapple with the ethical implications of this new technology, and mentioned that it will also require a shift in how electricity, electronics, and computational fabrics are taught in schools.
Mishchenko is both seeking new properties in extant materials and making novel materials and seeing what they’ll do. He’s also searching for useful applications for all of his materials.
A member of the audience asked Farrington if, given all of the new research in quantum physics, we have new data to resolve the Schrӧedinger’s cat conundrum? But she said no, the puzzle still stands. That is the essence of quantum physics: there is uncertainty in the (quantum) world, and both states exist simultaneously.
Another wondered why she chose to look for the tau lepton as evidence of the Higgs boson’s degradation and not any other particles, and she noted that tau was the simplest to see over the background even though it does not make up the largest share of the breakdown products.
An online questioner asked Prodromakis if memristors could be used to make supercomputers since they allow greater computational capacity. He answered that they could, in principle, and could be linked to our brains to augment our capabilities.
Someone then asked Mishchenko if his technology could be applied into biological systems. He said that in biological systems current comes in the form of ions, whereas in electronic systems current comes in the form of electrons, so there would need to be an interface that could translate the current between the two systems. Some of his materials can do that by using electrochemical reactions that convert electrons into ions. But the materials must also be nontoxic in order to be incorporated into human tissues, so he thinks this innovation is thirty to forty years away.
The last query regarded whether the participants viewed themselves as scientists or engineers. Farrington said she is decidedly a physicist and not an engineer, though she collaborates with civil and electrical engineers and relies on them heavily to build and maintain the colliders and detectors she needs for her work.
Prodromakis was trained as an engineer, but now works at understanding the physics of devices so he can design them to reliably do what he wants them to do. And Mishchenko summarized the difference between them by saying the engineering problems are quite specific, while scientists mostly work in darkness. At this point, he considers himself an entrepreneur.
Innovating in Chemistry
Speakers
David P. Mills, PhD The University of Manchester, 2021 Blavatnik Awards UK Chemistry Finalist
Matthew Powner, PhD University College London, 2021 Blavatnik Awards UK Chemistry Finalist
Building High Temperature Single-Molecule Magnets
David P. Mills, PhD The University of Manchester, 2021 Blavatnik Awards UK Chemistry Finalist
David Mills’ lab “makes molecules that have no right to exist.” He is specifically interested in the synthesis of small molecules with unusual shapes that contain metal ions, and using these as tiny molecular magnets to increase data storage capacity to support high-performance computing. Mills offers a bottom-up approach to this problem: he wants to make new molecules for high density data storage. This could ultimately make computers smaller and reduce the amount of energy they use.
Single-Molecule Magnets (SMMs) were discovered about thirty years ago. They differ from regular magnets, which derive their magnetic properties from interactions between atoms, but they still have two states: up and down. These can be used to store data in a manner similar to the bits of binary code that computers currently use. Initially, SMMs could only work at extremely cold temperatures, just above absolute zero. For many years, scientists were unable to create an SMM capable of operation above −259oC, only 10oC above the temperature of liquid helium, which makes them decidedly less than practical for everyday use.
Mills works with a class of elements called the lanthanides, sometimes known as the rare-earth metals, that are already used in smartphones and hybrid vehicles. One of his students utilized one such element, dysprosium, in the creation of an SMM that was dubbed, dysprosocenium. Dysprosocenium briefly held its magnetic properties even at a blistering −213oC, the warmest temperature at which any SMM had ever functioned. This temperature is starting to approach the temperature of liquid nitrogen, which has a boiling point of −195.8°C. If an SMM could function indefinitely at that temperature, it could potentially be used in real-world applications.
When developing dysprosocenium, the Mills group and their collaborators learned that controlling molecular vibrations is essential to allowing the single-molecule magnet to work at such high temperatures. So, his plan for the future is to learn how to control these vibrations and work toward depositing single-molecule magnets on surfaces.
The Chemical Origins of Life
Matthew Powner, PhD University College London, 2021 Blavatnik Awards UK Chemistry Finalist
The emergence of life is the most profound transition in the history of Earth, and yet we don’t know how it came about. Earth formed four-and-a-half billion years ago, and it is believed that the earliest life-forms appeared almost a billion years later. However, we don’t know what happened in the interim.
Life’s Last Universal Common Ancestor (LUCA) is believed to be much closer to modern life forms than to that primordial originator, so although we can learn about life’s common origins from LUCA, we can’t learn about the true Origin of Life. Where did life come from? How did the fundamental rules of chemistry give rise to life forms? Why did life organize itself the way that it did?
Matthew Powner thinks that to answer these vital existential questions, which lie at the nexus of chemistry and biology, we must simultaneously consider all of life’s components—nucleic acids, amino acids and peptides, metabolic reactions and pathways—and their interactions. We can’t just look at any one of them in isolation.
Since these events occurred in the distant past, we can’t discover it—we must reinvent it. To test how life came about, we must build it ourselves, from scratch, by generating and combining membranes, genomes, and catalysis, and eventually metabolism to generate energy.
In this presentation, Powner focused on his lab’s work with proteins. Our cells, which are highly organized and compartmentalized machines, use enzymes—proteins themselves—and other biological macromolecules to synthesize proteins. So how did the first proteins get made? Generally, the peptide bonds linking amino acids together to make proteins do not form at pH 7, the pH of water and therefore of most cells. But Powner’s lab showed that derivatives of amino acids could form peptide bonds at this pH in the presence of ultraviolet light from the sun, and sulfur and iron compounds, all of which were believed to have been present in the prebiotic Earth.
Chemistry Panel Discussion
Victoria Gill started this one off by asking the chemists how important it is to ask questions without a specific application in mind. Both agreed that curiosity defines and drives humanity, and that the most amazing discoveries arise just from trying to satisfy it. Powner says that science must fill all of the gaps in our understanding, and the new knowledge generated by this “blue sky research” (as Mills put it) will yield applications that will change the world but in unpredictable ways. Watson and Crick provide the perfect example; they didn’t set out to make PCR, but just to understand basic biological questions. Trying to drive technology forward may be essential, but it will never change the world the same way investigating fundamental phenomena for its own sake can.
One online viewer wanted to know if single-molecule magnets could be used to make levitating trains, but Mills said that they only work at the quantum scale; trains are much too big.
Other questions were about the origin of life. One wanted to know if life arose in hydrothermal vents, one was regarding the RNA hypothesis (which posits that RNA was the first biological molecule to arise since it can be both catalytic and self-replicating), and one wanted to know what Powner thought about synthetic biology. In terms of hydrothermal vents, Powner said that we know that metabolism is nothing if not adaptable—so it is difficult to put any constraints on the environment in which it arose.
He said that the RNA world is a useful framework in which to form research questions, but he no longer thinks it is a viable explanation for how life actually arose since any RNA reactions would need a membrane to contain them in order to be meaningful. And he said that synthetic biology—the venture of designing and generating cells from scratch, and even using non-canonical nucleic acids and amino acids beyond those typically used by life forms—is a complementary approach to the one his lab takes to investigate why biological systems are the way they are.
The Future of Research in the UK: How Will We Address the Biggest Challenges Facing Our Society?
Contributors
Stephen Brusatte, PhD The University of Edinburgh, 2021 Blavatnik Awards UK Life Sciences Laureate
Sinead Farrington, PhD The University of Edinburgh, 2021 Blavatnik Awards UK Physical Sciences & Engineering Laureate
Victoria Gill moderated this discussion with the Blavatnik laureates, Stephen Brusatte and Sinead Farrington. First, they discussed how COVID-19 affected their professional lives. Both of them spoke of how essential it was for them to support their students and postdocs throughout the pandemic. These people may live alone, or with multiple roommates, and they may be far from family and home, and both scientists said they spent a lot of time just talking to them and listening to them. This segued into a conversation about how the rampant misinformation on social media about COVID-19 highlighted the incredible need for science outreach, and how both laureates view it as a duty to communicate their work to the public by writing popular books and going into schools.
Next, they tackled the lack of diversity in STEM fields. Farrington said that she has quite a diverse research group—but that it took effort to achieve that. This led right back to public outreach and schooling. She said that one way to increase diversity would be to develop all children’s’ analytical thinking skills early on to yield “social leveling” and foment everyone’s interest in science. Brusatte agreed that increased outreach and engagement is an important way to reach larger audiences and counteract the deep-seated inequities in our society.
Lastly, they debated if science education in the UK is too specialized too early, and if it should be broader, given the interdisciplinary nature of so many breakthroughs today. Brusatte was educated under another system so didn’t really want to opine, but Farrington was loath to sacrifice depth for breadth. Deep expert knowledge is important.
Published since 2008, this series includes scholarly review articles in immunology and microbial-immunological interactions. The series was established and first edited by Noel Rose (Johns Hopkins). It is currently edited by Miriam Merad and Jerome Martin (Mount Sinai Ichan School of Medicine).
