leading SALK SCIENCE Into the FUTURE AN INTERVIEW WITH RUSTY GAGE, SALK PRESIDENT CONTENTS EXECUTIVE LETTER

Dear Friends,

I hope this message finds you and your family safe and well during this unparalleled period in our history. FRONTIERS 02 IN THE NEWS 12 In ways large and small, the COVID-19 pandemic has changed our world and given us all an appreciation for many things we took for granted. This time last year, few of us could have Leading Salk science 04 DISCOVERIES imagined that a trip to the grocery store, a simple hug from a friend or a handshake would into the future become a risk to our health. RESOLUTION This pandemic has also given us a renewed appreciation for the critical role scientific 26 research plays in protecting our health and our way of life. As we anxiously await the OBSERVATIONS distribution of effective vaccines, I take comfort knowing that the Institute’s founder, Jonas 20 Salk, faced a similar challenge with polio. Using basic science, he developed the first safe 30 IN MEMORIAM and effective vaccine, which helped halt polio epidemics. Science will once again prevail, Julie Law— this time over the novel coronavirus. Revealing RNA 34 SPOTLIGHT As 2020 comes to a close, I am filled with gratitude for the extraordinary efforts made by our faculty and administrative staff over the past year, which helped the Institute successfully “As 2020 comes to a navigate this pandemic. Under the leadership of President Rusty Gage, the Institute 44 EVENTS responded rapidly in March as the virus spread. A multidisciplinary team from across the close, I am filled with Institute implemented strategies to protect our researchers and staff and allow for the safe gratitude for the INSIGHTS pursuit of scientific research. And through this shared goal, stronger relations and new 24 48 DISCOVER SALK collaborations have been established among Salk staff, faculty, donors and trustees. extraordinary efforts Salk is fortunate to have Rusty Gage as its leader. It is well known that Rusty is a brilliant made by our faculty Gerald Pao— neuroscientist whose work continues to be at the forefront of scientific discovery. But it is Pushing the limits in his generosity of spirit, humility and focus on the future that also make him such a strong and administrative leader for Salk. He is known for his ability to bring people together and collaborate to science and in life advance both the scientific and administrative goals of the Institute. It is this unique set of staff over the past skills and experience that will help us build on Salk’s 60 years of bold research and position the Institute for even greater success into the future. A look at how that future is poised to year, which helped the unfold at Salk is the focus of this issue. Institute successfully NEXT GEN In this edition of Inside Salk you will also find the 2020 Salk Donor Honor Roll, our annual navigate this 28 acknowledgment and appreciation of those who have supported our work in the last fiscal year. Along with a summary report of the Institute’s fiscal health, we acknowledge the more pandemic.” Austin Coley— than 1,200 individuals, families, organizations and businesses who have supported Salk in the 2020 fiscal year (July 1, 2019 through June 30, 2020). Shaping academia for You will also discover how Salk scientists are pursuing their research and what makes them future scientists tick. Associate Professor Julie Law discusses how a chance event led her to devote her career to understanding the process of turning genes on or off. Staff Scientist Gerald Pao is at the forefront of scientific advancement, from studying the novel coronavirus to uploading brains to computers. And Postdoctoral Fellow Austin Coley not only conducts innovative brain research but also has a passion for advancing opportunities for greater diversity within the world of science.

The Institute’s future is bright because of its dedicated supporters, leadership and the ON THE COVER: faculty and staff who embody the spirit of Jonas Salk’s challenge to turn dreams into reality. On behalf of the Board of Trustees of the Salk Institute, I extend my deep appreciation for Together with Salk’s world-renowned researchers, your support of Salk science. You have truly made a difference. Salk President Rusty Gage is leading the Institute in bold efforts to tackle climate change, cancer, Sincerely, Alzheimer’s and much more.

Daniel C. Lewis Salk Board of Trustees Chair

WWW.SALK.EDU INSIDE SALK WINTER 2020 1 2 INSIDE SALK IN THE NEWS WINTER 2020 Project in 2019. funded through donations to The Audacious project focused on model plants that was This support bolsters the ongoing HPI store carbon and mitigate climate change. efforts to optimize plants’ natural ability to New grants are supporting the Institute’s SUPPORT WIDESPREAD GARNERS PLANTS INITIATIVE (HPI) HARNESSING SALK’S WWW.SALK.EDU WWW.SALK.EDU STORAGE RESEARCH STORAGE AND CAPTURE CARBON PLANT-BASED ADVANCE TO PROJECT ANNOUNCE ENERGY SEMPRA AND SALK of carbon amount the increase will that crops develop global diversity—to ofpower plant the use biochemistry—and and genomics, genetics, plant work in advance to scientists Salk enable will grant Fund Earth Bezos The crops. in sequestration carbon enhance to genes those utilizing then and plants model in sequestration carbon for genes increased on identifying focused project HPI It ongoing complements an capacity. carbon-storage plants’ the increasing of goal the with crop species prevalent most world’s of the six in mechanisms sequestration carbon- explore work will This soil. the in roots their via carbon atmospheric store and capture to soybeans, and corn as such of crop plants, ability the increase to efforts advance to Fund Earth Bezos the from million $30 received (HPI) Initiative Plants Harnessing Salk’s RESEARCH CHANGE CLIMATE INNOVATIVE INSTITUTE FOR SALK TO MILLION $30 DONATES FUND EARTH BEZOS Harnessing Plants Initiative.Harnessing Institute’s of the part project, Sorghum” Adapted Climate Through Carbon “Sequestering the of sponsor lead the be will Sempra donation, million $2 its With crisis. climate the address help to implementation and education research, sequestration and capture carbon based plant- advance project anew to announced SRE) (NYSE: Energy Sempra and Salk Michael and Joseph Noel. and Michael Chory, Joseph Law, Ecker, ToddJoanne Julie Busch, Wolfgang faculty Salk include team leadership HPI of the Members soil. earth’s the in it deep store and atmosphere the from removed Ecker, Julie Law, Todd Michael andJoseph Noel. From topleft: Wolfgang Busch, Joanne Chory, Joseph INSIDE SALK WINTER 2020 3 DISCOVERIES

The immune system is a finely tuned machine. It must IMMUNITY balance the release of its cellular army to deal with 07/2020 pathogens, such as the coronavirus, while reining in that army to stop the onslaught from attacking the body A histology image showing inflammation in colon epithelium. Weakening of regulatory T cell function induces infiltration of immune cells (small itself, which occurs in autoimmune diseases. Now, Salk blue dots) into colon epithelium (blue layer) and causes colitis. researchers have made two new scientific discoveries about how the immune system functions to keep the body healthy.

Salk Professor Susan Kaech examined the immune cells in the lungs, a significant site of damage during the COVID-19 infection. When we are first exposed to From left: Ye Zheng, Eric Chin-San Loo, bacteria or viruses, immune cells called Jovylyn Gatchalian and Diana Hargreaves. killer T cells destroy the infected cells to prevent the spread of the disease. In the second advance, Associate Killer T cells effectively provide long- Professor Ye Zheng, Assistant term protective immunity against the Professor Diana Hargreaves, co- invader, a fundamental concept behind first authors Jovylyn Gatchalian and vaccination. Kaech’s team, including first Eric Chin-San Loo, and colleagues author and then-graduate student Jun discovered a way to control regulatory JOURNAL OF Siong Low, found that the cells responsible T cells, immune cells that act as a EXPERIMENTAL for long-term immunity in the lungs can cease-fire signal, telling the immune MEDICINE be activated more easily than previously system when to stand down. Being 06/2020 thought. The insight could aid in the able to increase or decrease regulatory development of universal vaccines for T cell activity could one day help influenza and the novel coronavirus. treat numerous diseases including From left: Susan Kaech and Jun Siong Low. rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, lupus and WATCH www.salk.edu/kaech202012 even some cancers.

4 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 5 DISCOVERIES

NEUROSCIENCE AGING

METHOD TO DERIVE BLOOD VESSEL CELLS FROM SKIN CELLS SUGGESTS WAYS TO SLOW AGING

During a traditional lineup, eyewitnesses are either shown six photographs of individuals at the same time (simultaneous Professor and VP/ lineup) or presented one picture at a time (sequential lineup). eLIFE The paired comparison (PAR) method asks the eyewitness to CSO Martin Hetzer, 09/2020 choose the picture that is more similar to the culprit when shown co-first authors two photographs at the same time. A technique called signal detection analysis is then used to reveal the structure of the Simone Bersini and witness’s recognition memory and eliminate unconscious bias. Roberta Schulte, and colleagues have used skin cells called fibroblasts from People wrongfully accused of a crime often young and old patients to successfully KEEPING INNOCENT create blood vessel cells that retain NATURE wait years—if ever—to be exonerated. Many PEOPLE OUT OF JAIL COMMUNICATIONS of these wrongfully accused cases stem their molecular markers of age. The 07/2020 USING THE SCIENCE OF from unreliable eyewitness testimony. Now, team’s approach revealed clues as Professor Thomas Albright, Staff Scientist to why blood vessels tend to become PERCEPTION Sergei Gepshtein and colleagues have identified a new way of leaky and hardened with age, and lets presenting a lineup to an eyewitness that could improve the researchers identify new molecular WATCH www.salk.edu/albright202012 likelihood that the correct suspect is identified and reduce the targets to potentially slow aging in number of innocent people sentenced to jail. vascular cells. Skin fibroblasts were successfully reprogrammed into the smooth muscle cells (red) and endothelial cells (white) that surround blood vessels. The cells’ nuclei are shown in blue. Credit: Bersini, Schulte et al. CC by 4.0 TRAVELING BRAIN WAVES HELP DETECT HARD-TO-SEE NEW MOLECULE OBJECTS A drug candidate developed REVERSES REDOX by Senior Staff Scientist Professor John Reynolds, Professor Terrence BIOLOGY Pamela Maher and first Sejnowski, co-first authors Zac Davis and ALZHEIMER’S-LIKE 07/2020 NATURE author Gamze Ates of 10/2020 Lyle Muller, and colleagues have uncovered MEMORY DECLINE the Schubert lab, and details about the neural mechanisms previously shown to slow aging in brain cells, underlying the perception of objects. They successfully reversed memory loss in a mouse found that patterns of neural signals, called traveling brain model of inherited Alzheimer’s disease. The waves, exist in the visual system of the awake brain and are new research also revealed that the drug, organized to allow the brain to perceive objects that are faint CMS121, works by changing how brain cells or otherwise difficult to see. metabolize fatty molecules known as lipids. Pamela Maher

6 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 7 DISCOVERIES

COMPUTATIONAL BIOLOGY METABOLISM

GIANT LEAP IN DIAGNOSING FIRST IMMUNE-EVADING CELLS LIVER DISEASE CREATED TO TREAT TYPE 1 DIABETES Professor Ronald Evans, first author and former Chronic liver disease NATURE staff scientist Eiji Yoshihara, and colleagues have CELL represents a major 08/2020 made a major advance in the pursuit of a safe and METABOLISM global public health 06/2020 effective treatment for type 1 diabetes. Using stem-cell problem affecting technology, they generated the first human insulin- an estimated 844 producing pancreatic cell clusters able to evade the immune system. million people. A collaborative team These “immune shielded” cell clusters controlled blood glucose without of scientists, co-led by Salk Professor immunosuppressive drugs in mice, once transplanted in the body. Ronald Evans and including first

author Tae Gyu Oh and Senior Staff Schematic showing how the microbiome signature from stool WATCH www.salk.edu/evans202012 Scientist Michael Downes, have samples can be used to test for cirrhosis. created a novel diagnostic tool based on the microbiome—a complex collection of microbes that inhabit the gut. The non-invasive method quickly and inexpensively identifies liver Shown here, human islet-like organoids express fibrosis and cirrhosis over 90 percent insulin, which is indicated by the green color. of the time and could lead to improved patient care and treatment outcomes. From left: Michael Downes, Tae Gyu Oh and Ronald Evans.

COMMON DIABETES DRUG REVERSES INFLAMMATION IN THE LIVER CANCER The diabetes drug metformin has been GENES & prescribed to hundreds of millions DEVELOPMENT 09/2020 of people worldwide as the frontline THE Many cancer medications fail to effectively treatment for type 2 diabetes. Now, LOCATION, LOCATION, PROCEEDINGS OF THE NATIONAL target the most commonly mutated cancer Professor Reuben Shaw, first author ACADEMY OF Jeanine Van Nostrand and colleagues have shown SCIENCES genes in humans, called RAS. Now, Salk LOCATION: THE CELL the importance of specific enzymes in the body for 05/2020 Professor Geoffrey Wahl, first author Yao- metformin’s function. In addition, the new work MEMBRANE FACILITATES Cheng (Leo) Li and a team of scientists have uncovered details showed that the same proteins, regulated by metformin, RAS PROTEIN of how normal RAS interacts with mutated RAS and other controlled aspects of inflammation in mice, something proteins in living cells for the first time. The findings could aid the drug has not typically been prescribed for. Apart INTERACTIONS in the development of better RAS-targeted cancer therapeutics. From left: Reuben Shaw and Jeanine Van Nostrand. from clarifying how metformin works, the research has relevance for many other inflammatory diseases.

8 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 9 DISCOVERIES

GENETICS PROTEIN INTERACTIONS

HOW CELLS SOLVE THEIR IDENTITY CRISIS

Cancer is often the result of

GENES & DNA mutations or problems DEVELOPMENT with how cells divide, which 06/2020 can lead to cells “forgetting” what type of cell they are or how to function properly. Professor and VP/ CSO Martin Hetzer, first author Hyeseon Kang, Assistant Professor Jesse Dixon and colleagues have now provided clarity into how new cells A cell dividing into two cells during the process of mitosis. The remember their identity after cell division. microtubules (green) are shown pulling the chromosomes (red) to the These memory mechanisms could explicate opposite sides of the cell. problems that occur when cell identity is not IMAGING METHOD maintained, such as cancer. HIGHLIGHTS NEW ROLE FOR CELLULAR “SKELETON” PROTEIN

While your skeleton helps NATURE your body to move, fine METHODS skeleton-like filaments NEW MAPS OF CHEMICAL 08/2020 within your cells likewise MARKS ON DNA PINPOINT help cellular structures REGIONS RELEVANT TO MANY to move. Now, Staff Scientist Uri Manor and co-first authors Cara Schiavon and DEVELOPMENTAL DISEASES Tong Zhang have developed a new imaging method that lets them monitor a small In research that aims to illuminate the subset of these filaments, called actin. They observed how actin mediates an important NATURE causes of human developmental disorders, function: helping the cellular “power 07/2020 Professor Joseph Ecker, first author Yupeng stations” known as mitochondria divide He and colleagues have generated 168 new in two. The work could provide a better maps of chemical marks on strands of DNA— understanding of mitochondrial dysfunction, called methylation—in developing mice. The data can help which has been linked to cancer, aging and narrow down regions of the human genome that play roles in neurodegenerative diseases. diseases such as schizophrenia and Rett syndrome.

WATCH www.salk.edu/ecker202012

10 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 11 Two decades into the 21st century, the way science is conducted is changing dramatically. The Salk Institute, built with the implicit understanding that science is ever-evolving and institutions must adapt, is changing too. leading

FRONTIERS SALKSALK SSCIENCE CIEN into the To understand the future of Salk science, one only needs to look to its leader, current President and longtime faculty member Rusty Gage. From managing the COVID-19 crisis that threw the world into disarray, to advancing efforts in support of FUTURE equity and inclusion, Gage has been agile and collaborative, responsive and engaged. Even as he leads Salk’s response during these difficult and uncertain times, he balances a robust scientific research portfolio. From his lab to the President’s office, Gage has his eyes on the future of science at Salk, and on the significant shifts poised to transform the world of basic scientific research. His success lies largely in his approach: he pairs a disciplined and astute habit of observation with Inside Salk a deeply collaborative nature, where he seeks to sat down with lift diverse voices across the Institute to inform Rusty Gage to learn more about his background, his daily decisions while working strategically approach to managing a to advance scientific initiatives; recruit a new world-renowned Institute, generation of brilliant Salk scientists; and build and vision for Salk the financial and scientific resources necessary to science over the next move Salk into future. decade.

12 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 13 to find better ways to understand and treat As President of Salk, Gage brings a scientific conditions of the brain, such as Alzheimer’s, approach to leading: much like gathering data to depression, autism, bipolar disorder and test a hypothesis, he seeks input from a diverse schizophrenia. group of stakeholders and synthesizes it into a coherent picture to help guide the Institute. Raised in a military family stationed abroad, Gage—who arrived at Salk while founder and Gage went to high school in Italy before polio vaccine developer Jonas Salk was still attending college at the University of Florida and graduate school at Johns Hopkins University. He married his high school sweetheart and the couple moved to Sweden, where Gage completed a Fulbright fellowship and held a faculty position at Lund University. He joined the faculty at UC San Diego in 1985, and the family settled in San Diego, where his mother was raised and went to college. A dedicated mentor, he delights in the Gage lab reunions held every few years for alumni who travel back to Salk from around the world to share their research with their former colleagues and their former advisor. Gage worked alongside notables, such as Jonas Salk (pictured above). Leading with vision and collaboration When Rusty Gage, the Vi and John Adler Chair “In this new paradigm, RESEARCH AREAS for Research on Age-Related Neurodegenerative Disease, assumed the presidency of Salk in 2018, you not only read the he had decades of pioneering neuroscience literature, but you Technology Immunobiology papers to his credit. Since then, he has balanced aggregate data sets MARTIN HETZER SUSAN KAECH two equally demanding full-time jobs: president Vice President and Chief Science Officer NOMIS Chair of an elite, world-renowned institution that from all over the world Jesse and Caryl Philips Foundation Chair Professor and Director, NOMIS Center conducts innovative science, and leader of a Professor, Molecular and Cell Biology for Immunobiology and Microbial and build a theoretical Laboratory Pathogenesis distinguished neuroscience laboratory. model of the concepts “Salk’s future successes and breakthroughs, like “The future of immunobiology, both at Salk and Gage is one of the world’s preeminent you’re interested in, so our deep history of scientific discovery, will be the beyond, holds a great deal of promise. Not only are neuroscientists, known for overturning result of the teamwork of postdoctoral researchers, we learning more every day about the fundamentals longstanding scientific dogma that the brain you can decide what students, staff scientists and exceptional faculty—all of immunity, but we are also discovering how to does not make new neurons, with a 1998 study scientific questions to critically supported by the research centers, shared harness the immense power of the immune and revealing that “neurogenesis” does, in fact, occur core facilities and animal research department. cooperative defense systems and the microbiome to in select areas of the brain. pursue.” Bold and collaborative science is the hallmark of the target cancer, autoimmune diseases and infections, Institute, and the CSO office intends to bring that to help people live longer, healthier lives.” Since 2014, he has consistently been named spirit to all future endeavors, both at Salk and with Salk’s NOMIS Center for Immunobiology and Microbial RUSTY GAGE local and international partnerships.” one of science’s most highly cited researchers Pathogenesis is working to delineate the mechanisms that cause by Clarivate, indicating that his work has been The Office of the Chief Science Officer provides leadership in infectious diseases, understand the body’s response to injury or repeatedly judged by his peers to be notable for developing and implementing Salk’s overall scientific strategy, as infection, and explore why inflammatory processes spin out of well as overseeing research operations in support of this strategy. control under some circumstances. its significance and usefulness. And his lab, one of Salk’s largest, routinely delivers cutting-edge methodologies and ground-breaking discoveries

14 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 15 present—brings a deep respect for the Salk Salk’s collaborative Aging ethos of fostering collaboration between JAN KARLSEDER disciplines to encourage new discoveries. ethos means scientists Donald & Darlene Shiley Chair Professor, Molecular and Cell Biology Thus, with the concurrence in 2020 of in different areas are Laboratory Gage’s 25th year at Salk with the Institute’s accustomed to working Director, Paul F. Glenn Center for 60th anniversary and the heightened Aging Research interest in scientific research catalyzed across disciplines, not just “Understanding the complexity of the aging process by the COVID-19 pandemic, we felt it was and extending the human health span have become top within the Institute, but priorities of the Salk Institute, and will remain so in a fitting time to take a deeper look at his the future. Neurobiology, cell and molecular biology, vision for the future of science at Salk. also across the world. systems biology and computational biology will synergize (Inside Salk’s summer issue covered how to clarify complex age-associated pathologies such as the Institute is responding to the pandemic, Alzheimer’s disease, hearing loss, cardiovascular disease, including launching almost two dozen diabetes and cancer. The collaborative nature of Salk new research projects devoted to tackling will allow a uniquely cooperative approach through our “We are beginning to see a new biology that incorporates Optimizing Aging Initiative, which takes advantage of the COVID-19.) computation, mathematics and engineering,” says widespread expertise of Salk faculty.” Gage. “In this new paradigm, you aggregate data sets from all over the world and build a theoretical GERALD SHADEL Audrey Geisel Chair in Biomedical Science Looking Ahead model of the concepts you’re interested in, so you can Professor, Molecular and Cell Biology “The way science is done is changing,” Gage decide what scientific questions to pursue. Here, the Laboratory Director, San Diego Nathan Shock Center says. “The traditional way scientists conducted model is helping guide you to where the really critical life-science research was to base their questions are, and answering those questions is not “Aging is a complex process and not everyone ages the scientific inquiries around what skill sets they dependent entirely on your personal experience, skills same way, so researchers have to study its basic biology had. So, scientists formulated experiments or equipment. It may involve building a new instrument, from many different angles and in many different types of cells. The San Diego Nathan Shock Center will provide that they could address in their labs. Then they for example, so engineering becomes a big part of it. It critical infrastructure to help researchers with their looked at whatever results they got and, again, may point you in a therapeutic direction, so translation studies into aging, as well as pilot grants for experiments tried to solve the next question in terms of may be a part. Additional computation and refining of and support and encouragement for new researchers to their own experience.” theoretical models may also be necessary.” enter the field of aging research.” Aging is the greatest risk factor for many diseases. Salk Now, Gage explains, biological research is This new way of doing biological research plays to researchers seek to discover the fundamental causes of aging, so that everyone can live longer, healthier lives. undergoing a fundamental shift. The latter many of Salk’s strengths. The Institute’s emphasis on part of the 20th century saw the dawn of collaboration is exemplified by the research cores— the information age, and by the turn of the shared facilities that give Salk scientists access to CANCER millennium, computing power coincided cutting-edge technologies and staff with expertise with the generation of massive amounts of that individual labs may not have. Salk has 13 of these REUBEN SHAW William R. Brody Chair biological data; the era of big data has been cores, including biophotonics (advanced imaging), Professor, Molecular and Cell Biology launched, when vast quantities of information next generation sequencing and stem cells, to name Laboratory too unwieldy for human calculation can be just a few. Salk’s collaborative ethos means scientists

RESEARCH AREAS Director, Salk Cancer Center manipulated and analyzed for meaningful in different areas are accustomed to working across “Cancer is a complex and ever evolving foe, which is why patterns using computer algorithms (see Inside disciplines, not just within the Institute, but also across Salk researchers are joining forces to attack it from many Salk Winter 2019). The charge for the 21st the world. Many Salk faculty already have national different angles—metabolic therapies, immunotherapies, century, then, is to make sense of these massive and international collaborations in progress. Locally, targeted therapies, epigenetics and more. Working across scientific fields, we have continued to discover new and quantities of biological data scientists are now Salk’s faculty works closely with the UC San Diego unexpected therapeutic lines of attack to conquer cancer.” able to collect. And this, Gage contends, means Supercomputer Center, School of Engineering, School The Salk Cancer Center, one of seven National Cancer Institute conducting life-science research in a whole of Medicine and Moores Cancer Center and other (NCI)-designated basic research cancer centers, recently launched new way. organizations. the Conquering Cancer Initiative to harness new strategies against five deadly cancers: pancreatic, ovarian, lung, brain (glioblastoma) and triple negative breast.

16 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 17 19 RESEARCH AREAS WINTER 2020 INSIDE SALK TERRENCE SEJNOWSKI Francis Crick Chair Professor and Laboratory Head, Computational Neurobiology Laboratory Crick-Jacobs Center for Director, Theoretical and Computational Biology JOANNE CHORY Maryam R. Newman Howard H. and Biology Chair in Plant Plant Molecular Professor and Director, Biology Laboratory and Cellular Harnessing Plants Initiative Co-Director, WOLFGANG BUSCH Plant Molecular and Cellular Professor, Biology Biology Laboratory & Integrative Laboratory Harnessing Plants Initiative Co-Director, omputational omputational in single cells and it is now possible to record record to and it is now possible cells in single neurons of thousands of tens from simultaneously as such tools Computational in behavior. engaged approaches and new engineering learning machine and developing data these analyzing for essential are and cells of functions complex the for new theories take to Center will expand The Crick-Jacobs brains. decade.” next over the challenges on these planet. Society can no longer conduct business as business conduct longer no can Society planet. have a unique biologists plant usual, Salk’s and will be 10 years make. The next to contribution time that and within change, climate for critical have Initiative to Plants Harnessing the we expect the to enhance effort in an inroads made significant to help down CO2 to draw to plants of ability natural balance.” natural restore “It has become routine to sequence all the genes genes the all sequence to routine “It has become together life scientists, Crick Jacobs Center brings Salk’s computational scientists and engineers to develop the instrumentation and analytical tools that will be needed to tackle some of the biggest questions in science. PlantS a warming due to is at a crossroads “Humanity plant program recently launched highly ranked The Salk Institute’s approach to drawing the Harnessing Plants Initiative, a plant-based storing it stably in down carbon dioxide from the atmosphere and the roots of crops. C Biology

WWW.SALK.EDU Part of the Institute’s mission is training mission is training the Institute’s of Part and Gage scientists, of generation the next early more to adding forward is looking Salk’s of to the ranks researchers career who faculty, junior outstanding current as their and driven brilliant just as are questions in asking bold predecessors metabolism, genetics, about cancer, Of biology and the immune system. plant to Gageparticular importance is building and diversity of respect, culture on Salk’s that the inclusion. Gage firmly believes and skills necessary for bold creativity researchers require discovery scientific of ideas and experiences. with a diversity in 2018 acts as president One of his first an Office of Equity to establish was to and Inclusion, and Gage continues this champion efforts that advance goal. strategic think of this Salk might what Jonas Asked vision, Gage pauses for a long moment two “I think there’s responding. before Jonas parts of this vision for the future is the cooperation One appreciate. would backgrounds aspect, people of different He together on big questions. working should be serving had an idea that we but with a knowledge, deep scientific The other is humanistic perspective. the idea that science is changing all the time, and the building space has to fit the both embrace science. I think he would ideas.” ago 60 years Salk, who over Jonas Like would the world had a vision for how to an institution devoted benefit from Gage has a research, basic scientific of science— vision in which the future as bit as exciting be every Salk style—will its past. WWW.SALK.EDU “...the idea that science science that “...the idea time, the all changing is space building the and science.” to fithas the RUSTY GAGE A Glimpse of the Future A Glimpse the Institute Gage imagines that, in the near future, hubs for bioengineering, computation new will have an additional He envisions research and translation. to the iconic original in close proximity facility, specializing to house incoming researchers campus, will complement their work directions; in these new for which areas to established research and contribute Research (see Sidebars: known the Institute is already The original plans for the Institute envisioned Areas). Salk’s with Jonas in keeping buildings, such future that science changes understanding and the needs accomplish these ambitious of science change. To Salk will and recruitment, centers goals for facilities, year. next a campaign undertake WINTER 2020 Above and below: Renderings of the new facility facility of the new Renderings and below: Above that will be built on the original campus. It will bioengineering,include hubs for computation and translation. INSIDE SALK 18 OBSERVATIONS Revealing RNA Although Associate Professor Julie Law began college thinking she was going to become a physician, a summer job in a lab introduced her to the rewards of scientific research. She earned a bachelor’s degree in biochemistry and biophysics, as well as a doctoral degree in biochemistry (studying parasites), and she conducted postdoctoral research into the chemical tags on DNA that are known as methylation. As a member of the plant biology faculty at Salk, Law studies gene regulation.

Inside Salk sat down with Law to find out about the common themes underlying her research and to discuss what motivates her both in and out of the lab.

20 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 21 What is the “big picture” description of your “Plants have Are there any other scientists in your family? research? a very short life JL: Yes, on both sides. My mother is a microbiologist and worked in a hospital lab until she retired recently, and her work JL: In biology, there’s what’s known as the central dogma span, which allows us was my first exposure to science. My father and two of his three about the flow of genetic information. All the information is brothers are in STEM as well. My dad is an electrical engineer, hardwired in the DNA code, and then it has to be translated to look at things over and my two uncles are chemical engineers, so it’s safe to say I into other languages for the cellular machinery to understand. multiple generations and had a lot of exposure to science growing up. And RNA is one of those intermediary translation steps. But collect a large amount over several decades of research, it’s been realized that RNA How did you end up at Salk? plays a really fundamental role in a diverse set of processes of information over a JL: Salk is a really special place on many levels. For me, outside of that initial translation of information. So, since short time.” the huge drawing points were the strength of both the plant my graduate school days, my research interests have been biology program and the program studying gene regulation JULIE LAW grounded in trying to understand the different roles that and epigenetics. A lot of places independently study those RNAs—short copies of DNA segments—play in connection to processes, but very few bring them together across a diverse gene regulation, which, essentially, is the process of turning set of species and organisms. So it was a unique opportunity genes on and off. to join a world-renowned plant biology institute but also be Speaking of plants, at Salk one of the things surrounded by people studying the role of epigenetics in cancer you’re working on is the Harnessing Plants and the roles of genome structure in genome stability. We hear a lot about DNA and genes, but we Initiative, which seeks to mitigate global Not coming from a plant biology background, I was drawn to don’t really hear much about gene regulation. warming by using plants’ natural ability to the idea that studying processes from different angles and in What is it, and why is it important? capture and store carbon. How does your work different organisms can give you a great perspective on science. JL: Every cell within an organism has nearly identical genetic fit into the initiative? And having a place that values that kind of diversity was really information, yet not all cells look or act the same. In mammals, attractive to me. JL: The Harnessing Plants Initiative involves all of the plant a heart cell isn’t the same as an immune cell, for example, even biology faculty at Salk. We’ve banded together to use our though they share the same genetic blueprint. The way you Right now, due to the COVID-19 pandemic, collective expertise to address a globally important problem, get cellular diversity is by controlling which genes are turned you’re not able to work much in the lab. Are which, of course, is climate change. We want to identify or on and which ones are turned off, which is dictated by various there things you miss? generate plants that can shuttle more carbon—from CO in the types of chemical modifications. These modifications [also 2 JL: Definitely. Before all the working from home, it was quite atmosphere—into very long-lasting carbon-storage molecules exciting to get in, in the morning, seeing what people were called the epigenome] can include chemical tags that attach to in plant roots and the soil. But we don’t want to have to recreate doing and seeing what the day was going to bring. You never DNA, or the proteins that bundle DNA into a package that fits the wheel; engineering every step in the process, from taking quite knew what new experiments you were going to get to do. in the cell. And just as mistakes in the DNA code of a gene can result in disease, problems with gene regulation can also cause in the CO2 to generating these carbon-rich molecules, would be very difficult. So we want to understand how the plant The pandemic is probably also affecting what disease. you can do outside of the lab, but under normal normally turns on the machinery necessary to do that process circumstances, what do you like to do for fun? and then turn it up. My work involves identifying the gene You referred to mammalian cells, but you work JL: I grew up in Oregon, camping, doing a bunch of sports, regulatory machinery that will allow us to do that turning up. with plants. Can you explain why? riding a motorcycle. I don’t do as many of those things anymore, but I still like hiking and being outdoors. JL: I would say the strengths of studying gene regulation in plants are twofold: First, you can get viable genetic mutants, Were you always interested in science? You rode a motorcycle? That sounds pretty which allows you to manipulate the processes. You can figure JL: I was always interested in science and math. When I was adventurous! out, for example, if you tweak this gene, what goes wrong in my second year in college, I had the opportunity to do a JL: I guess I just grew up doing it, so I didn’t think about it as in the context of a living organism. In mammalian systems, summer internship in a lab. That opened my mind to all kinds being so adventurous, but—yeah. I ran into a tree once, with a these kinds of tweaks can be lethal, making it very hard to of different possibilities, and it’s what convinced me to switch lot of people watching, so that was pretty embarrassing at the understand the causes or consequences of particular changes. from premed to the biochemistry/biophysics degree. I was time. But it’s a good memory now. And second, plants have a very short life span, which allows us addicted to the lab from the start, and I had this realization that to look at things over multiple generations and collect a large you could work in a research lab, making new discoveries, and amount of information over a short time. get paid for it!

22 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 23 Although the pandemic has made his squid

PATH TO SALK project more difficult to pursue, Pao has Pao grew up in Spain, Germany and the United numerous other scientific endeavors to keep States. He had a keen interest in science from him busy, including his research involving the INSIGHTS an early age, and when he was in middle school, novel coronavirus. he asked his biology teacher to teach him about gene expression and the genetic code. The teacher refused, telling Pao that he was too COVID-19 RESEARCH young, so Pao begged his father to help him At Salk, Pao and colleagues have engineered a find a mentor in molecular biology. fake virus that has the exterior of the coronavirus, allowing them to study a mutation in the spike His father obliged, and at the age of 12, From studying the novel coronavirus to protein; the protein is what enables the virus to Pao began spending time at the Center for pull itself inside the host cell. “We’re interested downloading brains to computers, Staff Molecular Biology at the Universidad Autónoma in a mutation in the spike protein that makes the Scientist Gerald Pao is at the forefront de Madrid, where he learned about gene virus possibly more infectious,” says Pao. “When expression in the model system Drosophila we introduced the mutated virus into human cells of scientific advancement. For Pao, melanogaster, a fly. A few years later, at the in the lab, we observed that the cells became being a staff scientist gives him the urging of Professor Gines Morata, Pao decided infected five times more efficiently than with the to attend the University of California San Diego nonmutated virus.” Although these findings are freedom to explore a broad range of (UC San Diego) due to the strength of molecular preliminary and were conducted using a virus biology programs both there and at the Salk risky scientific endeavors that could that mimics the novel coronavirus, they could Institute, across the street. help guide vaccine design for specific coronavirus yield pioneering results. For his undergraduate degree in molecular strains. biology, Pao explored the evolution of Pao is also working on creating fluorescent fake “A staff scientist can be an tyrosine kinases—enzymes that serve as on/ viruses that light up, which will allow scientists off switches—and the complex nature of to determine whether viruses stick to surfaces, incredibly enabling position, protein interactions. In his sophomore year, such as face masks, or how the viruses move in Pao connected with Salk Professor Tony air-conditioning systems. where I can pursue a greater Hunter, whose seminal discovery of tyrosine variety of topics that are difficult phosphorylation (the mechanism behind the LEISURE TIME on/off switches) led to the development of an In his free time, Pao likes to play volleyball and to approach in more traditional entire class of anticancer drugs called tyrosine surf. He also enjoys rock climbing and has been positions—and I have a lot of inhibitors, one of which is the leukemia drug known to sneak up to Yosemite for a weekend of Gleevec. interests!” says Pao. big wall climbing on El Capitan. “Tony has an amazing, encyclopedic breadth of knowledge and excitement for science,” says FUN FACTS Pao. “He is like the wise man on the mountain Pao paid for college by working as a professional that you can consult about any scientific query.” model in Europe. He modeled in commercials Pao completed his PhD in molecular biology for athletic brands and walked the runway for Gerald Pao jointly at UC San Diego and Salk, and he now fashion brands, such as Benetton. Pao also speaks works as a staff scientist in Hunter’s lab. German, English, Mandarin, Cantonese and Pushing the limits in Spanish fluently. DAY-TO-DAY science and in life Prior to the COVID-19 pandemic, Pao spent FUTURE PROJECTS many months of every year in Japan, taking Pao and colleagues are working on a new skin samples from ocean-dwelling bigfin reef project that allows neural data from the brain to squid for his research. Squid have special be downloaded to a computer. The researchers proteins, called reflectins, that allow them to are taking the data from fly and fish brains and camouflage themselves by tuning the amount converting it into a computer model to create a of light reflected by their skin—manipulating program that behaves like a real fly or fish. what scientists call the optical density. Pao is “Essentially, we are downloading a fly brain onto trying to hack these reflectins so that scientists the computer,” explains Pao. “It’s not just science can more easily view internal processes, such fiction. We want to create artificial intelligence that as the activity of the brain. is based on real biology.”

24 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SPRING 2020 25 26 INSIDE SALK RESOLUTION WINTER 2020 (red). (See Discoveries to learn more.) (red). (SeeDiscoveriestolearn more.) cells immune lung other by surrounded T (blue), killer cells called cells, immune specialized by (green) tissue lung in mounted is defense This COVID-19. or finding that could help address infections thought—a like influenza previously than activated researchers easily more be lab, Kaech the demonstrated from that long-term immunity in the lungs can work recent In WWW.SALK.EDU greatest “Our ancestors.” tois begood responsibility Salk Institute legacy at the Discover your JONAS SALK JONAS

You, too, can have a transformative atransformative have You, can world. too, the changed Salk Jonas Whether you would like to put your donation to work today or work donation to put today your to like you would Whether Plan your future. We can help you get started. started. get We you help can future. your Plan Gifts of any size can help accelerate innovation, support the next next the support innovation, help accelerate can size of any Gifts Leaving a gift to the Salk Institute in your will or by beneficiary or beneficiary by will your in Institute Salk the to agift Leaving Making a lasting impact through a planned gift can be simple. simple. be can gift aplanned through impact alasting Making manage cancer, fight climate change, treat Alzheimer’s, and more. Alzheimer’s, treat change, climate fight cancer, manage impact on the future of humanity. future on the impact lets you provide for your family and support the Salk Institute. Salk the support and for family you provide your lets designation will support foundational research that could help could that research foundational support will designation generation of scientists and enable life-changing discoveries. life-changing enable and generation of scientists benefit us after your lifetime, you can find a charitable plan that that plan charitable find a can you lifetime, your after us benefit Contact Cheryl H. Dean, Esq., at at Esq., Dean, H. Cheryl Contact [email protected] or 858.500.4884 [email protected] help finding the right gift plan. plan. gift right the help finding

for for “Exposure is the best thing to change Shaping attitudes. People need to see that academia there are successful Black scientists for in academia.” future Austin Coley, though only at Salk since 2019, condition in my family, as there is a stigma around mental has already taken an active role in everything health in the Black community,” says Coley. “I want to uncover scientists the neural mechanisms of schizophrenia to improve our from conducting innovative research around understanding of the disease, mental health awareness the brain to spearheading a wide variety of and outcomes.” outreach activities. In his third year in graduate school, Coley came to San Diego Raised by a single mother, Coley grew up in multiple towns in to attend the Society for Neuroscience annual conference, New Jersey as his family moved to seek better opportunities where he learned about a new award to fund minority

NEXT GEN and avoid troubled neighborhoods. He was a star football researchers on their path to full-time faculty positions: player in high school, but the summer after his senior year he the NIH Blueprint Diversity Specialized Predoctoral to experienced a life-altering injury. Postdoctoral Advancement in Neuroscience Award. Coley was the perfect fit. “My first love was football,” says Coley. “But I wrecked my hamstring, so I could no longer play. My entire life changed.” Winning the award jump-started Coley’s career, as it funded the last two years of his PhD and provided funding for his Outside of football, Coley had always enjoyed biology and entire postdoctoral studies. With independent funding, Coley anatomy classes. “Understanding how the body worked could choose nearly any scientist in the country to work and how diseases affected the body fascinated me,” he says.

Coley with for his postdoc, and he chose renowned neuroscientist So, he started exploring university biology programs. and Salk Professor Kay Tye. The historically Black college and university (HBCU) “Kay offered to support not only my scientific interests, North Carolina Central University caught his attention, as it but also my social justice activities outside of her lab. It was offered a brand-new science complex and enthusiastic faculty. clear that she believed in me,” says Coley. Once there, despite his excitement for biology, Coley struggled with his first exams. In the Tye lab, Coley is now studying the populations of neurons that are affected in anhedonia, the inability “I had come to college to study science, yet I failed my first to experience pleasure, which is a core symptom of round of biology and chemistry exams. I was scared,” he schizophrenia and depression. He is using calcium imaging Austin shares. “I decided that I would learn how to study and really techniques to examine the neurons in the frontal lobe of apply myself for the next exams. This would be my last shot. the brain, called the prefrontal cortex. His goal is to see if If I failed again, I would drop out of the major.” manipulating certain neurons in the prefrontal cortex helps Coley threw himself into his academics. He spent his days in alleviate symptoms of schizophrenia and depression. the library, deciphering chemical equations and memorizing Outside of the lab, Coley is also an active member of Salk’s biological definitions. He aced his next exams. community. Currently, he is co-chairing the newly formed After undergrad, Coley went on to complete his master’s Black Association at Salk (BAS), which aims to unite and degree in cell physiology at Case Western Reserve University support Black employees through social hours, speakers and but was disappointed with the lack of support, encouragement professional development opportunities. He is also working and representation of Black scientists in his program. with Salk’s Diversity and Inclusion Task Force to invite more When he applied for his PhD in neurobiology at Drexel Black speakers to the weekly seminar series. University College of Medicine, Coley knew he wanted “Exposure is the best thing to change attitudes. People need to be in a lab that championed minorities in science. to see that there are successful Black scientists in academia,” Professor Wen‑Jun Gao welcomed Coley into his lab to work says Coley. “I would love to be a quiet scientist, focus on my on the molecular components involved in schizophrenia. work and go home, but right now I need to do everything I can “When I was growing up, my uncle was diagnosed with to improve the scientific ecosystem for the next generation schizophrenia, but I had no idea. We didn’t talk about his of Black scientists.”

28 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 29 his BA in chemistry from Indiana University in establishment of the first medicinal chemistry 1965. He first came to Salk later that year as a lab at Salk, where he worked to make derivatives graduate student in the lab of late Salk professor of neuroprotective natural products that have and immunologist Melvin Cohn, while working much-improved medicinal, chemical and on his PhD in cell biology at the University of pharmacological properties over the parent California San Diego. Schubert then moved to the compounds. For example, the lab found that Pasteur Institute, in Paris, for his postdoctoral fisetin, which naturally occurs in strawberries, fellowship under the direction of Nobel Laureate prevents memory and learning deficits in François Jacob before returning to Salk in 1970 mouse models of Parkinson’s and Alzheimer’s as a member of the faculty. He established the diseases. A synthetic derivative of fisetin is now first neurobiology undergoing the laboratory at studies necessary for the Institute. In moving into clinical that capacity, he trials. Additionally, developed and they found that a characterized a synthetic derivative large number of of the curry spice nerve, glial and curcumin, called muscle cell lines J147, improves that have served behavioral and

IN MEMORIAM as the basis for pathological numerous important symptoms discoveries by labs associated with around the world. Alzheimer’s, Schubert served as traumatic brain “We are deeply saddened by Dave’s a professor and the “THE WORLD, NOW injury and stroke. LONGTIME SALK passing. He was one of the earliest head of the Cellular This compound is graduate students at Salk and spent Neurobiology MORE THAN EVER, currently in a phase PROFESSOR DAVID close to 55 years of his scientific Laboratory until his 1 clinical trial for career here,” says Salk President passing. IS IN DESPERATE the treatment of SCHUBERT PASSES Rusty Gage. “Dave will be greatly Alzheimer’s. missed and we are forever thankful Schubert’s diverse NEED OF PEOPLE AT THE AGE OF 77 for his contributions to our research body of work LIKE DAV E .” Schubert also community.” includes research believed in giving on various factors back to the local San Renowned cell biologist and Salk Professor JAN LEWERENZ Jan Lewerenz, a senior physician at influencing SENIOR PHYSICIAN, ULM UNIVERSITY HOSPITAL Diego community David Schubert passed away on August 6, Ulm University Hospital, in Germany, the health and and served as a and one of Schubert’s former development of member of the 2020, at the age of 77 in La Jolla, California. postdoctoral researchers, adds, “I will nerve and muscle County of San Diego He was known for the development of novel remember Dave as one of the best cells, on a type of cancer called neuroblastoma, Scientific Advisory Board as well as the National human beings I had the privilege to and on genetically modified crops. Water Reuse Panel for San Diego County. screening techniques that allowed his team know. Without him my life would to identify naturally occurring chemicals that have been different … The world, now In recent years at Salk, Schubert and his wife, Between his graduate work and faculty more than ever, is in desperate need of Salk Senior Staff Scientist Pamela Maher, appointments, Schubert spent close to 55 can slow or prevent the neurological damage people like Dave.” developed a novel screening technique to test combined years at the Salk Institute. He passed that occurs in neurodegenerative disorders, for naturally occurring chemicals that can away due to B cell lymphoma and is survived by Schubert was born in 1943 in prevent the type of nerve cell death found in his wife, Pamela Maher, his son, Bruno Schubert, such as Alzheimer’s disease. Indianapolis, Indiana, and earned neurodegenerative diseases. This led to the and his three grandchildren.

30 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 31 IN MEMORIAM SALK MOURNS TWO LONGTIME DONORS Glenn and Simner will be deeply missed. Their partnerships enabled the type of scientific discoveries that change the world for the better and the Institute’s science is stronger today because of them.

PAUL F. GLENN TINA SIMNER

Longtime Salk donor Paul F. Glenn Due to his generous financial support, Committed Salk donor Tina Chef Jeffrey Strauss for the event, an passed away on September 29, Paul F. Glenn Centers for the Biology of Simner passed away on October accomplishment she took great pride in. Aging Research were established not only 2020, at his home in Montecito, In recent years, Simner turned her at the Salk Institute, but also at Harvard, 4 at her home in La Jolla. Her focus to supporting the Salk Women & California. He was an attorney Stanford, MIT, the Mayo Clinic, Princeton, support and leadership over Science program, generously donating Einstein College of Medicine, University of by education, and had a fruitful the years, especially of the Salk to the program and lending her skills to Michigan and the Buck Institute. The Glenn fundraising events. She also provided her career as a commodities trader. Foundation has funded more than $100 Women & Science program, fashion industry expertise, chairing the Glenn founded the Glenn million in basic research since its inception. cannot be overstated. Design and Discovery Fashion Showcase Foundation for Medical Research Salk’s Glenn Center was established in in 2017 along with Salk Professor Janelle January 2009 with a $5 million award from Simner moved to the San Diego area from Ayres. in 1965. His philanthropic the Glenn Foundation and the award has New York, where she’d run a fashion Simner had a love for life, was an focus was ahead of its time: to been extended three times since then. accessories business with her late husband accomplished artist, a devoted friend and fund research that would lead The Salk Institute extends its heartfelt for 25 years. She began her support of Salk generous to those less fortunate than herself. by way of Symphony at Salk, the Institute’s condolences to the Glenn family and the The Institute extends its deepest to treatments and therapies to main fundraising event, held every summer. Glenn Foundation. condolences to the Simner family. extend the quality of a person’s In addition to her generous giving, Simner health during their lifetime. played an instrumental role in recruiting

32 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 33 34 INSIDE SALK SPOTLIGHT WINTER 2020 AND BIOPHYSICS AND IN CANCER BIOLOGY SCIENTISTS TOP WELCOMES SALK here at Salk.” stem from their research endeavors see what innovations and collaborations the Salk Institute, and we are excited to and Pallav represent the bright future of says Salk President Rusty Gage. “Daniel accomplished early-career scientists,” “We are elated to bring on highly two disease. treatments for, breast cancer and heart understanding of, and find new fresh perspectives to advance an Hollern and Pallav Kosuri will bring biophysics, respectively. Daniel in the fields of cancer biology and hired new two assistant professors Over the summer, the Salk Institute

WWW.SALK.EDU WWW.SALK.EDU Pallav Kosuri Daniel Hollern Research ServiceAwards (NRSA)andtheAitch Foundation Award. S. Pagano Award, consecutive NIHRuthL.Kirschstein National State University andholdsnumerous awards includingtheJoseph Hollern earnedhisPhDincellandmolecularbiology from Michigan biology to studytheanti-tumor immuneresponse. patients, hewillleverage functional genomics andexperimental tumor growth. Inorder to improve treatment strategies for cancer therapies, immunecelldynamics andthemechanismscontrolling takes amulti-disciplinary approach to investigate responses to cancer where management ofadvanced disease isvery challenging.Hollern cancers being researched inSalk’s Conquering Cancer Initiative), lab willfocus ontriple-negative breast cancer (oneofthe five deadly that can improve thetreatment ofcancer patients. Inparticular, his as itsrenowned NCI-designated Cancer Center to pursue research NOMIS Center for Immunobiology andMicrobial Pathogenesis aswell postdoctoral fellow inthelabofCharlesPerou. Hollern joinsSalk’s University ofNorth Carolina at ChapelHill,where hewas a Assistant Professor DanielHollerncomesto Salkfrom the a Fulbright Scholarship. the Columbia University distinctionaward for doctoral defense and including theTitus M.Coan Prize for Excellence inBasicResearch, two patents for histechnologies, alongwithnumerous accolades and molecularbiophysics at Columbia University. He currently holds Originally from Sweden, Kosuri completed hisPhDinbiochemistry the way to innovative new treatments. understand why theheartexperiences mechanical failure andto point will applythisknowledge to examine heartdisease inorder to better of how mechanical movement gives rise to biological function.He their organization intissues, inorder to create anintegrated theory visualize andmeasure themovements ofsinglemoleculesandmap and editingDNA.Specifically, heisdeveloping technologies to biological machines—from muscles contracting, to enzymesreading Laboratory. Hiswork aimsto better understand thephysics of Zhuang. At Salk,hewilljointhefaculty oftheIntegrative Biology University, where hewas apostdoctoral fellow inthelabofXiaowei Assistant Professor Pallav Kosuri joinsSalkfrom Harvard INSIDE SALK WINTER 2020 35 SPOTLIGHT

Aging is the most significant risk factor for human CONSORTIUM LED BY disease. Human cells and tissues age at different rates SALK TO RECEIVE depending on their intrinsic properties, where they are in the body and environmental exposures. Yet, EXPECTED $5 MILLION scientists do not fully understand this variability and how it contributes to overall human aging, risk for FOR NEW CENTER disease or therapeutic responses.

TO STUDY CELLULAR The Salk Institute will establish a world-class San AGING IN HUMANS Diego Nathan Shock Center (SD-NSC), a consortium with Sanford Burnham Prebys Medical Discovery Institute and the University of California San Diego to study cellular and tissue aging in humans. The Center will be funded by a grant from the National Institute on Aging of the National Institutes of Health and is expected to total $5 million over the next 5 years.

Salk Professor Gerald Shadel led the successful grant proposal and will be director of the center. Professors

Gerald Shadel Rusty Gage Rusty Gage, Martin Hetzer and Tatyana Sharpee will lead several of the key research and development core facilities. November 2019 The SD-NSC will be one of a network of eight Nathan Shock Centers nationwide, which are named after FIVE SALK Nathan Shock, Director of the Gerontology Research An all-time-high number of participants—nearly Center at National Institutes of Health for nearly RESEARCHERS 3,000—took part in the sixth-annual Pedal the Cause 35 years and regarded by many as the “father of event on November 16, 2019, which included multiple gerontology.” AWARDED 2020 Martin Hetzer Tatyana Sharpee cycling courses, a 5K, spin classes and kid-friendly PADRES PEDAL THE activities. Proceeds from the event support innovative CAUSE GRANTS cancer projects with a major emphasis on collaborative, translational research that offers a clear path to clinical A record $3.1 million was raised by last trials. The Salk Institute and BridgeBio SALK INSTITUTE AND year’s Padres Pedal the Cause event, Padres Pedal the Cause provides grants to cross- Pharma, Inc., BRIDGEBIO PHARMA funding cancer research at five San Diego institutional teams of scientists and physicians at the Salk announced a facilities, including the Salk Institute. Institute, Sanford Burnham Prebys Medical Discovery three-year collaboration to advance cutting-edge academic COLLABORATE TO Institute, Moores Cancer Center at UC San Diego Health discoveries in genetically driven diseases toward therapeutic and Rady Children’s Hospital. The annual event has raised applications. Under the partnership, BridgeBio will help fund ADVANCE THERAPIES Salk Professors Ronald Evans, Tony Hunter, Susan more than $13 million to fund 62 cancer research projects research programs from Salk’s world-renowned innovative Kaech and Reuben Shaw, and Assistant Professor FOR GENETICALLY since its inception. cancer research, with the eventual goal of developing new Dannielle Engle, were among the collaborative mix of therapeutics for patients in need. DRIVEN DISEASES researchers and medical professionals to receive This year’s Padres Pedal the Cause event, originally scheduled funding this year. for November 1, 2020, has been moved to spring 2021.

36 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 37 SPOTLIGHT

REWARDING COLLABORATION GRANTS ROSE HILLS GRANT These collaborative grants provide seed funding to DANNIELLE ENGLE OUT-OF-THE-BOX large, ambitious ideas involving three or more Salk Assistant Professor Dannielle Engle was named The Rose Hills investigators. Foundation’s 2020-2021 Innovator Grant Program awardee. The award provides $100,000 for Engle to investigate how the sugar IDEAS: THE 2020 CA19-9 makes pancreatic cancer more aggressive, increases metastatic spread, and interacts with metastatic sites. As most SALK INNOVATION pancreatic cancer patients are diagnosed with metastatic disease, blocking CA19-9 interactions may intercept metastatic spread. GRANT AWARDS

JOHN REYNOLDS 2020 INNOVATION GRANTS Every year, the Salk Innovation JUAN CARLOS IZPISUA BELMONTE RUSTY GAGE Grants Program awards fund out- SATCHIN PANDA of-the-box ideas from Salk labs that Professors John Reynolds, Juan Carlos Izpisua Belmonte and Rusty Gage will examine the hallmarks One of the holy grails of circadian biology research is to understand what determines hold significant promise but may not of aging in animal models to determine whether mobile whether an animal is active during the day (diurnal) or during the night (nocturnal). yet have the track record to attract DNA elements, called LINE1 retrotransposons, can To begin to answer this question, Professor Satchin Panda will measure changes attention from more traditional be manipulated to slow or reverse aging to create an in hormones and gene activity as two species of animals—the night monkey and innovative healthy aging intervention. mouse—switch between diurnal and nocturnal lifestyles. One potential outcome of funding sources. this work will be strategies for improving the health and life quality of shift workers, Awarded semi-annually by a a growing fraction of the worldwide workforce. competitive peer-review process, this program is critical to catalyze emerging science with the power to E D W A R D S U S A N K A E C H STITES redefine the future and has led to a Cancer cells are host of impactful discoveries since The RAS protein metabolically greedy, is frequently which often leads to its launch in 2006 by the forward- mutated in some of nutrient depletion within thinking minds of then-Board chair MARTYN GOULDING the most difficult- and around a tumor. Irwin Jacobs and his wife, Joan, who AXEL NIMMERJAHN to-treat cancers, Professor and Director SUNG HAN have supported the program every including lung of the NOMIS Center for Professor Martyn Goulding, Associate Professor Axel and colon. To better understand the contribution of Immunobiology and Microbial Pathogenesis Susan Kaech year since its existence. Nimmerjahn and Assistant Professor Sung Han will RAS to cancer, Assistant Professor Edward Stites hypothesizes that this lack of nutrients starves immune cells Congratulations to all of the investigate how sensory signals from the skin, the will activate a particularly deadly version of RAS that might otherwise recognize and eliminate the tumor. The biggest sensory organ, are processed as they travel in the microscopic worm C. elegans, a widely used team will map the nutrient landscape of different tumors, 2020 winners! to the brain. The project will potentially reveal new model organism. Subsequent genetic and chemical with the goal of identifying specific nutrients (metabolites) targets for sensory dysfunction, which can occur with screens will help to reveal new drugs and therapeutic that boost immune cell effectiveness. Results will help to chronic pain and autism spectrum disorders. strategies for treating RAS-associated cancers. improve current anti-cancer immunotherapies.

38 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 39 SPOTLIGHT

DANNIELLE JOANNE CHORY ENGLE WINS NEW RECEIVES INVESTIGATOR PEARL MEISTER AWARD GREENGARD AWARD

Howard Hughes Medical Institute Investigator and Professor Joanne Chory, who is the Howard H. and Maryam R. Newman Chair in Plant Biology and director of the Plant Molecular and Cellular Biology Laboratory at Salk, has been awarded the 2020 Pearl Meister Greengard Prize, a preeminent international award recognizing outstanding women scientists. The award recognizes Chory for fundamentally changing researchers’ understanding of plant growth and development, and for her groundbreaking efforts to combat climate change. The Pearl Meister Greengard Prize was founded by the late Nobel Prize-winning neuroscientist Paul Greengard, in Edward Stites honor of his mother. EDWARD STITES Joanne Chory RECEIVES NIH DIRECTOR’S NEW INNOVATOR AWARD

RONALD EVANS Professor Ronald Evans, director Assistant Professor Edward Stites has been named an NIH of Salk’s Gene Expression Director’s New Innovator for 2020 as part of the National Dannielle Engle RECEIVES NOMIS Laboratory and March of Institutes of Health’s High-Risk, High-Reward Research Dimes Chair in Molecular and Program. The award “supports unusually innovative research Assistant Professor Dannielle Engle has AWARD Developmental Biology, has from early career investigators,” according to the been awarded a New Investigator Award been awarded a 2020 NOMIS Distinguished Scientist and Scholar Award by the NIH and provides $1.5 million for a 5-year project. For his from the Tobacco-Related Disease Research NOMIS Foundation, a Swiss foundation that supports high-risk basic research. project, Stites will use mathematical and biological approaches Program (TRDRP) to examine how tobacco The award, which totals $2.5 million, recognizes scientists for their “outstanding to identify strategies to convert failed therapeutics into use promotes cellular changes that lead to contributions to the advancement of science and human progress through their effective agents. pancreatic cancer. Engle will receive more pioneering, innovative and collaborative research,” according to NOMIS. The than $1 million over 3 years to develop award will enable Evans to decode how different parts of the body, including the new models for examining how tobacco brain, endocrine glands, gut, liver, immune cells and the microbiome, cooperate to carcinogens (cancer-causing substances) maintain health. Ronald Evans lead to tumor development and metastasis.

40 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 41 SPOTLIGHT

In just three months, the Institute’s summer fundraising campaign did better than we could laboratory practices, and were provided professional have ever dreamed, thanks to supporters who development opportunities. After completing the believe in the power of science. Though it was EDUCATION program, 93.4% of students said they were interested a difficult time for many, you still committed in pursuing a career in STEM (science, technology, to supporting life-saving science during this OUTREACH GOES engineering and math). challenging period. Every gift, big and small, VIRTUAL Additionally, the Institute’s popular Mobile Science makes a significant difference during this critical Lab was transformed into a virtual experience. It point in human history. When the COVID-19 pandemic closed brought volunteer scientists into distance-learning local schools this past year, Salk’s classrooms to conduct a combination of minds-on and With this support, our scientists will blaze ahead Education Outreach department had to hands-on biotechnology activities, including a DNA with their life-changing research into coronavirus, get creative to continue its mission of extraction, with middle school classrooms all over cancer, climate change and other major San Diego. The Virtual Mobile Science Lab is on pace teaching and inspiring students to pursue problems facing the world. Already, they are to reach more than 770 students from more than 20 forging innovative collaborations in bold areas of careers in science. They quickly adapted schools in nine different San Diego zip codes by the and rolled out virtual options for popular end of the calendar year. research, all in pursuit of what Institute founder programs, to great success. Jonas Salk laid the groundwork for: solving the Finally, both the Summer Scholars program and world’s seemingly most intractable problems for the Virtual Mobile Science lab took advantage of The Heithoff-Brody High School Summer Scholars the health and prosperity of humankind. SciChats, an additional EO program. The interactive program normally accepts 10 to 12 students each sessions allowed students to learn over Zoom from year to intern at Salk. Because the program had FROM EVERYONE AT SALK: THANK YOU! volunteer scientists about their research and what it’s to go virtual, it was modified to the Introduction like to be a scientist. By the end of 2020, 53 SciChats A special thanks to The Peggy and Robert to Research Science and Communication Virtual will have been held, compared to an average of six in Matthews Foundation and our Institute Council Program and accommodated 76 students from previous years. members for going above and beyond! 40 different schools, selected from a pool of over 400 applicants hailing from 10 states and two To learn more about Education Outreach, as well as additional countries (Mexico and India). Over access virtual tools for learning, visit four weeks, these high school students completed www.salk.edu/education virtual lab simulations, learned about common

42 INSIDE SALK WINTER 2020 WWW.SALK.EDU SALK LAUNCHES THE POWER OF SCIENCE ELLEN POTTER SYMPOSIUM VIRTUAL LECTURE SERIES GOES VIRTUAL In the spring, Salk introduced the On October 24, Education Outreach Power of Science Lecture series, held its annual Ellen Potter Symposium, a new format to allow faculty to featuring Uri Manor, director of Salk’s share recent research with donors Advanced Biophotonics Core. Each that occurred throughout the fall, teachers are invited to Salk to hear year. Faculty speakers included from Salk faculty and researchers in a Professors Janelle Ayres, Ronald seminar environment, then collaborate

EVENTS Evans, Martin Hetzer, Susan Kaech, with colleagues to apply what they have Satchin Panda, Reuben Shaw and learned to their lesson plans. Assistant Professor Dannielle Engle on topics ranging from collaborative cancer research; circadian biology; infectious disease; and aging. Find more information and view videos at www.salk.edu/powerofscience.

SALK JOINS VIRTUAL WELLBEING PANEL On October 28, Susan Kaech, Salk Professor and Director of the NOMIS Center for Immunology and Microbial Pathogenesis, joined a panel of speakers hosted by Union Bank entitled “Women, Wealth and Health: Connecting Well-Being and Philanthropy in the Age of COVID.” She joined Jennifer Alcorn, deputy director of Philanthropic Partnerships for the Bill and Melinda Gates Foundation; and Eric Verdin, president and CEO of the Buck Institute for Research on Aging, in discussing health and aging research, community involvement and health-related philanthropic efforts.

Susan Kaech

44 INSIDE SALK WINTER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK WINTER 2020 45 THE Groundbreaking Salk discoveries POWER on the go! Where Cures Begin is the official podcast of the Salk Institute for Biological Studies. In each episode, co-hosts Allie Akmal and Brittany Fair interview Salk researchers about their bold research efforts and learn about OF the scientists’ lives outside of the lab. Join us to hear how Salk researchers are making advances in the neuroscience of perception, developing cures for cancer, understanding the novel coronavirus and more.

The podcast is available on iTunes, Google SCIENCE Play and anywhere you listen to podcasts. COVID-19. CANCER. CLIMATE CHANGE. To learn more, visit www.salk.edu/podcast

The Salk Institute is tackling some of the most SEASONS 1 & 2 (AVAILABLE NOW) pressing problems of our time. SEASON 3 (COMING EARLY 2021): Like the scientific giants that preceded them, Salk’s internationally renowned and award-winning scientists are relentless in their pursuit Thomas Albright on using Satchin Panda on the neuroscience to make benefits of staying in sync of transformative discoveries in infectious disease, aging, plant eyewitness identification with your biological clock biology, cancer, brain disease and much more. Partner with us to more accurate Staff scientist perspective: learn about the Institute’s bold research, support the next generation Ronald Evans on Gerald Pao on examining of bright minds, and enjoy events that blend art and science in discovering the key to how hormones affect gene how the novel coronavirus unique ways. Together, we can continue our legacy of changing the activity spreads and exploring the world for the better. transparency of squids Julie Law on defining the epigenome and why it’s Postdoc profile: Sign up to be the first to know about our latest discoveries and important in health and Nikki Lytle on making disease be informed when our campus opens for architecture tours and scientific advances in public events: www.salk.edu/subscribe Dmitry Lyumkis on pancreatic cancer researching how coronavirus proteins are And more! assembled and bind to Molly Matty, postdoctoral fellow, in Season 2, Episode 12. promote viral infection Salk programs offer a range of ways to get involved. Learn about Salk science and support vital research.

Rusty Gage President

Rebecca Newman Vice President, External Relations

Steven Johnson Chief Communications Officer

Kristina Grifantini Director, Scientific Communications and Media Relations

Allie Akmal Media Relations Manager

Brittany Fair Science Writer

Curtis Ippolito Development Writer

Aaron Howard Video Communications Manager EDUCATION OUTREACH SALKEXCELLERATORS Salk offers a wide variety of Designed for young business Liz Hincks programs to inspire—and professionals and community Director of Digital and launch—the next generation members committed to support- Graphic Communications of scientists. The Education ing Salk scientific discovery, Outreach program includes a Salkexcellerators offers a unique John McDonagh Mobile Science Lab, Heithoff- opportunity to support cutting- Senior Web Developer Brody Scholars curriculum edge research while connecting and teacher training. with like-minded people. Stephanie Harada Web Designer SALK SCIENCE & MUSIC SERIES PRESIDENT’S CLUB Chris Keeney Four remarkable Sunday The President’s Club helps recruit Photographer afternoons bring together top-tier scientists, acquire cutting- virtuosos from the worlds edge technology and embark on SALK WOMEN & SCIENCE SYMPHONY AT SALK Oliver Yambao Showcasing the achievements This annual concert under of science and music. innovative research initiatives. Senior Graphic Designer of Salk’s women of science, the stars features the incredible PARTNERS IN RESEARCH this program welcomes comm- San Diego Symphony and a ARCHITECTURE TOURS Sara Jacobsen Partners in Research invest The Salk Institute has been unity and business leaders guest artist while supporting Graphic Designer in the future of cancer, aging, described as one of the most interested in inspiring women the Institute’s world-renowned Alzheimer’s disease and diabetes significant architectural sites to embrace scientific research research and award-winning Amy Cao research by incorporating their in the United States and has personally and philanthropically. education outreach programs. Science Illustrator philanthropic support for Salk garnered accolades for its in their estate plans. design and preservation. CHAIRMAN’S CIRCLE INSTITUTE COUNCIL Visionary donors in the Chairman’s This group of highly engaged Circle provide the vital resources individuals focuses on advancing Salk researchers need to pursue Salk scientific initiatives. breakthrough science. Visit the Salk Institute at www.salk.edu.

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