APART & TOGETHER RESPONDING TO THE PANDEMIC

INSIDE SALK COVID-19 EDITION CONTENTS PRESIDENT’S LETTER INSIDE SALK INSIDE

Dear Friends,

COVID-19 FEATURE DISCOVERIES Jonas Salk notably said, “our greatest responsibility is to be good ancestors.” Living 02 20 now, in these extraordinary times, we as individuals and an Institute recognize that we must respond with clarity and morality. Analysis : A closer look at COVID-19 EDITION 30 IN THE NEWS At the time of this magazine’s printing in late June, it remains hard to overstate the the novel coronavirus impact of the novel coronavirus infection, COVID-19. The pandemic has impeded world economies and education, and halted personal freedoms often taken for 36 RESOLUTION granted, including the simplicity of an in-person interaction. As the effort to slow the spread of COVID-19 continues, the world is reminded of how crucial basic scientific COVID-19 FEATURE research is to human health. 04 42 SPOTLIGHT It is also impossible to ignore the parallels between the fear and anxiety we are Apart but together: How experiencing today with the fears of a prior generation who faced the polio virus. At the Institute is responding 46 EVENTS its height, polio paralyzed or killed half a million people globally each year. Today, polio is 99 percent eradicated globally, thanks to the effective polio vaccine. to the pandemic “The Salk Institute has While the world works on treating and defeating COVID-19, it is an unprecedented period for global scientific collaborations. Indeed, the Salk Institute has tapped its tapped its experts in experts in virology, immunology and infectious disease on potential approaches COVID-19 FEATURE and put together a committee to identify and review COVID-19 research proposals. virology, immunology 12 Already, 11 new research proposals have received preliminary approval to proceed. and infectious disease A conversation with The Institute, like organizations across the world, is being impacted financially. Most Martin Hetzer of our revenue streams have dropped, and safety measures implemented to prevent on potential approaches transmission of the virus have required the cancellation of events, including our 25th anniversary Symphony at Salk fundraiser in August. One of the bright spots is and put together a that many of our Symphony at Salk sponsors continued their contributions to this committee to identify COVID-19 FEATURE event despite the cancellation. Because Symphony at Salk proceeds support our 14 unrestricted annual operations, their generosity provides essential funding to help us and review COVID-19 navigate this period. New COVID-19 research research proposals.” In the midst of the COVID-19 pandemic, the killing of George Floyd in Minnesota projects in May sparked protests across the world. The abhorrent racial discrimination and violence against Black people are devastating reminders of the vital importance of how our mission to better humanity must extend beyond science. Just as “every cure has a starting point” is championed as our mantra in research toward eliminating disease and other issues threatening human health, it so too must be our mindset OBSERVATIONS in doing our part to eradicate systemic racism and injustice. For each, the essential 32 starting point is an absolute commitment to being constructive forces for progress and agents of meaningful change. We stand with our Black community, and our Eiman Azim– commitment is unwavering. Decoding dexterity In this issue, you will learn more about how the Institute improves global well-being on multiple fronts and continues to be a faithful steward of Jonas Salk’s vision. I trust the updates contained in these pages—ranging from new coronavirus research to profiles of our innovative scientists—inspire your hope in our shared future. Know 38 INSIGHTS that all of us at the Salk Institute look forward to the day when we can safely come together again. Until then, please stay safe and healthy.

Nasun Hah— Sincerely, Next gen sequencing

40 NEXT GEN ON THE COVER: Fred H. Gage Molly Matty— As COVID-19 spreads across the world, President organizations like the Salk Institute are What worms can teach us mobilizing to respond.

1 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 1 INSIDE SALK INSIDE ENVELOPE (E) PROTEIN This small structural protein (purple) is involved ANALYSIS with the virus’ life cycle, including the assembly of other proteins and development of the Much remains to be understood COVID-19 disease. COVID-19 EDITION about SARS-CoV-2, the newly LIPID MEMBRANE emergent virus causing the This membrane (gray) is composed of a double COVID-19 pandemic infection. layer of polarized fat molecules. Similar to how Here is some of what scientists dish soap washes away oily grease, soap breaks down this fat membrane, destroying the virus. know about its structure, to date. This is why handwashing is recommended to prevent the spread of coronavirus.

ENVELOPE (E) PROTEIN MEMBRANE (M) PROTEIN This is the most abundant structural protein (yellow) in the virus. It defines the shape of the LIPID MEMBRANE lipid membrane, which surrounds the virus, and may help it evade the immune system.

SPIKE (S) PROTEIN This structural protein (red) is what gives the MEMBRANE (M) PROTEIN coronavirus its name, as the proteins, seen through an electron microscope, cause the virus to appear to have a corona or crown of spikes. These spikey proteins hook onto human cells SPIKE (S) PROTEIN and pull the virus inside, where the virus can co-opt cellular machinery and begin churning out copies of itself. Because of its essential role in transmission, the S protein is now a key target for vaccines and therapeutic antibodies.

Learn more about Salk research and COVID-19

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2 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 3 INSIDE SALK INSIDE Pandemics, past and present

In 1960, when Jonas Salk founded his eponymous Institute, he was arguably the COVID-19 EDITION most famous scientist in the world for having developed the first safe and effective vaccine for a terrifyingly contagious viral disease called polio. At its peak, polio paralyzed or killed hundreds of thousands of people (primarily children) annually worldwide.

In 2020, humanity is facing another highly infectious viral disease, COVID-19, whose long- term effects are not yet known. Although polio and COVID-19 are caused by different viral species that affect different systems in the body, there is a chilling superficial similarity in the way both diseases can cause difficulty breathing. Indeed, it is easy to think of today’s ventilator as yesterday’s iron lung.

Polio, which is transmitted via fecal-oral routes, is, paradoxically, thought to have become a public health threat due to improvements in public sanitation in the early 20th century. Before sanitation improved, and polio was more widespread, most people encountered polio as babies, while they still had their mothers’ immune antibodies as protection against the virus. Once public sanitation cleaned up water and waste, children didn’t encounter the virus until they were older and no longer had their mothers’ protective antibodies. Older children (and some adults) whose immune systems had never previously encountered polio were immunologically vulnerable.

Like polio, COVID-19 exploits a vulnerability in the immune system’s armor: because the SARS-CoV-2 virus—the novel coronavirus that causes COVID-19—appeared in humans recently, our immune systems have no experience with the virus—and sometimes have difficulty fighting it.

“Long-term immunity, also called ‘immune memory,’ is a process by which we develop the ability to have protective immune responses later on that are targeted to pathogens that we have encountered before,” says Professor Susan Kaech,

4 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 5 NOMIS Chair and director of Salk’s NOMIS Center and will also help teach researchers which vaccines “While some things like writing manuscripts and SALK INSIDE for Immunobiology and Microbial Pathogenesis. “So may be the most protective. Scientists around the globe analyzing data can be achieved remotely,” says our immune system learns from the first exposure, have been racing to find solutions in a monumentally Professor Gerald Shadel, the Audrey Geisel Chair and the memory of the pathogen is then imprinted in collaborative effort, while also maintaining social/ in Biomedical Science and a member of the CMT, our immune system in specialized cells, aptly named physical distancing—a challenge for work that often “most science requires hands-on experiments and memory T and B cells. Those memory cells can persist needs to be conducted in close quarters in a lab. collaborations that cannot be achieved remotely.

for many years, sometimes an entire lifetime, and allow Secondly, there are many moving parts to a world- COVID-19 EDITION us to respond swiftly and robustly to clear out that During this public health crisis, the Salk Institute’s class scientific institute like Salk, in addition to same pathogen if encountered later on.” leadership and scientists have faced a conundrum: the labs: scientific core facilities, animal resources, how to rapidly shut down all non-essential research development, communications, safety, human Because SARS-CoV-2 is thought to be more infectious, as effectively as possible while minimizing loss of resources, IT, security, facilities—the list goes and deadlier, than seasonal influenza, many people data and doing everything possible to assist with the on and on. Each decision has a butterfly effect unfolding public health crisis. around the world are becoming critically ill and on most, if not all, operations, making the task of reducing operations at the Institute as a whole very straining medical systems, which are not designed to “Even though it was a difficult “We realized early on we needed to take swift action to challenging.” handle so many additional patients simultaneously. minimize opportunities for viral transmission through decision [to potentially lose many the community, help that community stay connected, In addition to the gravitational pull of Salk’s research Thus, COVID-19 represents a perfect storm of hours of experimental research], and safeguard valuable research materials and projects and daily operations, the Institute’s historically threats, one that requires an unprecedented response. helping to ‘flatten the curve’ of for the future,” says Professor Martin Hetzer, Salk’s VP/ significant architecture typically draws 150 visitors Immunologists are focused on several areas related CSO. “Thanks to the flexibility and innovation of the to campus every day, many of them international infections and hospitalizations to COVID-19, such as developing a protective vaccine entire Institute, staff and scientists alike, we were able tourists who come to witness one of the finest or anti-viral drugs; understanding the difference in was of the utmost importance.” to move quickly to protect the Salk community in the examples of modernist architecture in the world. immune response between those who have severe face of this growing pandemic.” But, as early indications of COVID-19’s rapid spread MARTIN HETZER illness versus mild illness; determining what is driving VP/CSO suggested that the public health crisis was likely to lung damage and death seen in some patients; and get much worse, the Institute closed the campus to figuring out which types of memory cells generated visitors on March 4. against the virus are the most protective. This latter An iconic campus “I’m grateful that we were ahead of the curve and information could help generate immuno-therapies Next, the team started to plan for what would happen responded fairly quickly,” Hetzer says. “At the time our for severely infected patients until there is a vaccine, goes into “maintenance if the Institute had to close down. Time was of the taskforce convened, the situation was still evolving mode” essence; as each day passed, news of COVID-19 very rapidly, but we felt it was important to act with became grimmer and the possibility of shutting down an abundance of caution to protect both visitors to the campus—and its experiments—looked more Salk as well as the Salk community. Even though it and more likely, even before official state shutdown was a difficult decision, helping to ‘flatten the curve’ Enacting a partial shutdown of a research institution orders. of infections and hospitalizations was of the utmost is different from shutting down many other kinds of importance.” organizations. Many experiments that involve biological By the time California Governor Gavin Newsom samples or plant and animal studies cannot simply be issued a stay-at-home order to residents on One of the greatest challenges in shutting down paused. The Institute’s 52 labs and approximately 1,200 Thursday, March 19—the first state in the nation was evaluating which experiments could continue scientists, students and staff sustain research projects to do so in response to the COVID-19 pandemic— and which would have to be paused or terminated. that result in the publication of upwards of 300 papers Salk, for several weeks, had already been preparing Salk’s maintenance mode entailed operating at a per year in leading academic journals. Salk has critical its temporary closure. The week of March 9, the cell lines, plants and animals that need a physical Institute finalized processes for working from minimal level to conserve resources, both in terms human presence to ensure their survival. home; determined which staff would be considered of personnel and of materials that could be affected essential for continued work on campus; and by supply-chain disruptions. In some cases, cells can On Monday, March 2, 2020, Hetzer began meetings with decided how to wind down laboratory research for be frozen and later thawed to resume work, but in the Institute’s Crisis Management Team (CMT)—a the campus-wide “maintenance mode” of limited other cases, projects that are too costly in terms of combination of faculty and administrators—to evaluate activity until more information around the threat resources must be discontinued. Due to a rigorous the emerging public health crisis and to make plans for of the pandemic—and how best to mitigate risk— one-week evaluation process, the Institute was able how the Institute would respond. became available. to establish how resources could be channeled toward

6 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 7 INSIDE SALK INSIDE experiments that could not be paused without losing processes to not only minimize any real risks but also months or even years of work. alleviate fears.” Science continued

“Labs and administrative departments moved A vital part of ensuring safety is providing sufficient very quickly, within the short span of a few days, to personal protective equipment to staff, despite shortages. Finding ways to transition from working at a completely reconfigure their labs and experiments,” Nicole Lack, senior director of Procurement Services, lab bench to working remotely is a significant

says Salk President and Professor Rusty Gage. “And feels this issue keenly: “This situation has definitely had challenge for many researchers. But Salk COVID-19 EDITION scientists have risen to the occasion with not only that, but many people at Salk wanted to donate an impact on our supply chain for essential components creativity and resolve. blood to the San Diego Blood Bank and extra personal like personal protective equipment and CO2, an element protective equipment to local hospitals. The way the Salk needed for many lab functions. We’ve had to respond Just as a few examples, Professor Geoffrey community pulled together was extraordinary.” quickly to uncertain supplies—looking for new suppliers Wahl’s lab used time away from the lab to revise or finding ways to ration items, for example—to help and submit paper revisions, write grants and Mark Bouchard, director of Environmental Health & the Institute maximize safety while continuing critical hold virtual happy hours as well as a journal club to stay connected. Assistant Professor Safety (EH&S), worked quickly to ensure new safety experiments.” Dmitry Lyumkis’ lab implemented a “back-to- measures for the Institute as well as manage fear around In addition to adapting to the new reality on campus, school” virtual program consisting of biweekly contagion. “Due to the COVID-19 epidemic, we had to the Institute established tools and protocols for remote presentations on a research topic, journal rapidly instill enhanced infection control procedures club meetings, and a guest lecture on Fridays. work using collaboration platforms, such as Slack, and such as maintaining a social distance of 6 feet, wearing Many labs have also focused on computational videoconferencing technologies, like GoToMeeting and additional personal protective equipment (PPE), and projects that can be done remotely, carrying out Zoom. performing decontamination procedures at an increased bioinformatics, image processing and algorithm design. frequency,” he says. “Something as simple as a cough “Obviously, working from home is a completely different in the lab can cause anxiety, so we also aim to provide a experience than working in an office or lab,” says “While some things like writing Professor Jan Karlseder, the Donald and Darlene quick response and good communications around safety Rebecca Newman, VP of External Relations. “It presents manuscripts and analyzing Shiley Chair, says that many lab members continue to feel anxious about how the change a number of challenges that can take some adjustment. data can be achieved remotely, in work space will impact their careers and their While everyone misses the physical energy of being most science requires futures. “We’re trying to solve that by staying on the campus, I am amazed at how quickly the Salk on top of everyone’s experiments. We’re talking community has adapted to the use of all the technologies hands-on experiments and about them; we’re discussing many papers as that can keep us connected and highly productive. There collaborations that cannot be journal clubs, and we’re trying to plan out what is a new appreciation and understanding of colleagues’ we will do when research fully resumes,” he says. roles across the Institute and a positive attitude that we achieved remotely.” To help early career researchers navigate the are moving through this crisis together.” GERALD SHADEL challenges of having their work disrupted, often AUDREY GEISEL CHAIR IN BIOMEDICAL SCIENCE AND A while needing to take care of young children all MEMBER OF THE SALK’S CRISIS MANAGEMENT TEAM day at home, Salk formed a Career Development Committee, led by Associate Professor “Many Salk scientists were Sreekanth (Shrek) Chalasani and Vice President for Equity and Inclusion Mallory Zaslav, to already conducting research identify professional opportunities that can be that is highly relevant to conducted remotely. (See sidebar on the postdoc experience on page 11.) COVID-19.” During maintenance mode, the Institute planned JANELLE AYRES for stages of ramp up in accordance with federal, PROFESSOR AND CHAIR OF THE state and local guidelines and in consultation COVID-19 RESEARCH COMMITTEE with local and peer institutes across the country. In late May, Salk published a guidebook detailing operations for phased returns and in June, the Institute shifted from its maintenance mode to Phase 1 in conjunction with an ease of the Above: The Wahl Lab collaborates virtually through a Zoom statewide shutdown. Phase 1 entailed adding meeting work space during the COVID-19 pandemic.

8 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 9 INSIDE SALK INSIDE temperature checks to the Institute’s entry points; “Polio is a great and highly relevant example. Once there has expressed appreciation for the way people have reconfiguring work spaces; and implementing shift is a COVID-19 vaccine, it will be a phenomenal tool to pulled together to continue groundbreaking research work so that more research could safely continue, control this new threat, and hopefully that will re-instill a as well as pursue ways to tackle the coronavirus. Once while still requiring staff to work remotely whenever widespread commitment to vaccination compliance.” it is safe to do so, the Institute will also bring back possible. its highly anticipated scientific and public events, “I hope this will remind us even Kaech adds, “I hope this will remind us even more how including the annual Symphony at Salk. Despite a gradual resumption of activities on campus, important vaccines really are, and the essential role they

there is no return to “normal” anytime soon. All tasks more how important vaccines play in public health. We have to look at vaccines at the “We look forward to the day when scientists, staff COVID-19 EDITION that can be done off-site—such as writing papers or really are, and the essential role population level, not the individual level, and realize they and visitors can all return to our iconic campus,” says providing administrative support—will continue to save lives. Sadly, I think some people have forgotten this Gage. “We are confident that scientific endeavors be remote for the immediate future. Large gatherings they play in public health. We because we haven’t had anything threaten our society across the world will help mitigate this public health and events have been moved to virtual platforms have to look at vaccines at the globally, quite like this, in the past 40 or so years, like crisis and prevent further tragedies.” or postponed. Day-to-day lives, and research, have polio and smallpox once did.” population level, not the individual LISTEN www.salk.edu/podcast/COVID19 fundamentally changed for the time being, but Salk’s Despite the challenges of the pandemic, everyone at Salk scientists continue to adapt and rise to the challenge. level, and realize they save lives.”

SUSAN KAECH NOMIS CHAIR AND DIRECTOR OF SALK’S NOMIS CENTER Tackling the novel FOR IMMUNOBIOLOGY AND MICROBIAL PATHOGENESIS PERSPECTIVE FROM A POSTDOC: coronavirus Ayres says the committee is especially looking for CORINNE LEE-KUBLI innovative proposals for science to address the pandemic that isn’t necessarily going to be done someplace else. Salk has roughly 200 postdoctoral fellows whose science Like scientists all over the world, Salk researchers “Researchers within the Salk Institute became really is being impacted by the COVID-19-induced maintenance are eager to contribute to efforts to put an end to this ignited by the pandemic; they want to make a difference, mode. While some scientific models, such as the tiny pandemic and prevent future ones. On March 24, the they want to contribute to the response, so they are worm C. elegans, can be easily frozen for months at a faculty COVID-19 Research Committee was created, developing diagnostics and performing fundamental time, experiments involving other model systems, such as organoids—tiny three-dimensional organs in a dish—cannot chaired by Professor Janelle Ayres and composed of research that is necessary for identifying candidate be so easily paused. experts in immunology, infectious disease and virology, to therapeutic targets,” she says. For details about new Lee-Kubli in center (fourth from right) with Chalasani lab (July 2019). identify and shape Salk’s research approach to COVID-19. research projects approved by Salk’s COVID-19 Research Thus, some essential experiments have continued in order to Committee, see pages 14-15. not disrupt critical projects. Corinne Lee-Kubli, a postdoctoral the children. “My husband built the kids a playhouse in “Many Salk scientists were already conducting research researcher in the Chalasani lab, just finished the last part of the backyard, so that’s helped our family spend more time that is highly relevant to COVID-19,” says Ayres, who A vaccine against the virus that causes COVID-19 is likely her project testing a new technology, called sonogenetics, outside.” Soaking up some San Diego sun helps her family holds the Helen McLoraine Developmental Chair. many months away, but the disease is a powerful reminder which activates neurons non-invasively using ultrasound. stay positive, despite challenging times. of the importance of fundamental biological research, She is thankful that she was almost finished with her project Salk faculty whose research has direct relevance to which seeks to understand at a basic level how living things when the maintenance mode went into effect. Now, she is “I am also grateful to have a supportive and flexible mentor,” COVID-19 include Ayres, who was already studying function. looking forward to reviewing the scientific literature, writing says Lee-Kubli. “Dr. Chalasani has kept our weekly lab pneumonia and acute respiratory distress syndrome up her results and submitting her manuscript to an academic meetings as well as our individual meetings, to help us The research that goes on at Salk every day—bringing about journal. (ARDS, which occurs in COVID-19 patients); Kaech, who develop obtainable goals during the closure.” studies immunity to infections, including via vaccines; new understandings in infectious disease, cancer, aging, “Reviewers may suddenly have a lot more time to read new Greg Lemke, who studies receptors that regulate the metabolism, neuroscience, plant biology and more—is a The Career Development Committee is also working on research articles, and I imagine they’ll be more conscientious kind of insurance policy against future health threats, both immune response and prevent the “cytokine storms” that about what they request in terms of follow-up experiments, initiating a virtual seminar series, where postdocs can known and unknown. Jonas Salk did not develop the polio develop in COVID-19; Satchin Panda, who is studying since most labs are closed,” says Lee-Kubli. “Theoretically, present their work and practice job talks. Other faculty long-term gene activity in COVID-19 patients; Marga vaccine out of the blue in 1955; for many years before he we could see a surge in scientific publications, which would members, such as Associate Professor Julie Law, are Behrens, who is studying the effects of virus-induced developed his vaccine, Salk had been studying the influenza be very exciting!” hosting virtual happy hours for trainees to socialize and maternal immune activity on brain development of virus. It was the critical insights he gained by developing release stress. The committee is also suggesting that faculty a vaccine for influenza that later allowed him to conquer In addition to her research project, Lee-Kubli plans to use her offspring; Tony Hunter, whose discovery of molecular members discuss individual development plans with each polio: by 1979, polio had been eradicated in the United time away from the lab to start writing a draft of a research switches called tyrosine kinases led to anti-cancer drugs trainee to set career goals and next steps. States. grant and prepare her applications for her first faculty called tyrosine kinase inhibitors, several of which are position. “I think one of the most helpful things I’ve found for “I appreciate how the coronavirus and the associated risks in clinical trials for their ability to block activation of maintaining productivity is sticking to a schedule.” “Vaccines have proven to be one of the very best approaches were taken seriously by Salk,” says Lee-Kubli. “Knowing that immune cells and potentially reduce ARDS; Dmitry to save lives and improve human health. They have been A dedicated schedule has also helped Lee-Kubli and her I could trust the decisions of Salk’s coronavirus Task Force Lyumkis, who investigates protein molecules made by so effective that the threats they prevent no longer feel like husband juggle two young children at home. Every day the helped alleviate stress and take pressure off the situation. viruses and how the insights inform the design of novel threats,” says Assistant Professor Edward Stites, who in parents take turns, with one working while the other watches Now, I can focus on my work.” vaccines and antivirals; and others. addition to being a cancer researcher is also a physician.

10 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 11 “The Institute’s approach cells help or hinder immunity; and finding which SALK INSIDE cellular targets may be best for therapies or vaccines. since its founding has been Some of the labs are recalibrating their already- to understand fundamental relevant research to focus on the novel coronavirus, biological processes, in order while others are beginning exciting new lines of work. to make discoveries that can COVID-19 EDITION inform treatments and cures.” Q: In the beginning of June, you developed a plan to move the Institute to a phase of MARTIN HETZER limited shift work for researchers, with plans for VP/CSO additional phases following local and federal guidance. What do you see as the next steps for resuming scientific research at the Institute? to figure out how to bring activity—and therefore lab population density—down to a minimum so that MH: For now, we are adapting to new guidelines as anyone who had to go to work to carry out essential they are released by public health authorities, which functions (caring for animals, for example) could do entail moving the Institute to new phases in a very so in a safe manner, following CDC guidelines. These thoughtful, staggered process to maintain the social distancing requirements needed to keep everyone were not easy decisions. Many research projects safe. Each individual lab has developed plans for how unfold over not just days or weeks but over months or they can safely expand research activities as well as even years, so we wanted to avoid an undue burden A Conversation with move quickly on the new COVID-19 areas of research. in terms of loss of valuable experimental material We have also determined appropriate steps as to how and insights. The labs, including my own, had to we can bring back the different administrative units grapple with these difficult questions over a very few who support reopening, in an effective way. MARTIN days. Remarkably, based on an impressive level of Very early on in the face of the COVID-19 cooperation, researchers were able to wind down In addition, we are continuing to recruit new faculty, pandemic, you set up a COVID-19 Task Force activities significantly in that short period of time, because we are not merely focused on getting and other committees to handle the rapidly while also thinking of ways to bring unique scientific through the next few months under the pandemic, HETZER changing day-to-day circumstances for the approaches to better understanding the novel but are also looking ahead to the best ways to tackle Salk Vice President and Chief Science Officer thousand-plus employees at the Institute. At coronavirus. other major health problems that the world faces, the same time, you and other faculty began such as climate change, Alzheimer’s, cancer and evaluating ways that Salk’s unique research diabetes to name a few. In the last few months, Salk Vice strengths could help tackle COVID-19. What Q: Could you talk a bit more about that, and Salk’s efforts to help stem COVID-19? President and Chief Science Officer did it take to so swiftly change course for Q: Any parting thoughts? such a prolific and productive Institute? MH: The Institute’s approach since its founding Martin Hetzer spearheaded the has been to understand fundamental biological MH: Very much in the spirit of Jonas Salk, I believe MH: We took several big steps early on when the processes, in order to make discoveries that can that foundational basic research plays a central role pandemic was first coming to light. At that time, Institute’s efforts to respond to the inform treatments and cures. So we wanted to take in mitigating the impact of a crisis such as COVID-19, in early March, it was still a very rapidly evolving a similar approach to the novel coronavirus and and also to prevent such crises in the future. So, if pandemic from both an administrative situation, and we chose to act with an abundance ask where we could make the biggest impact. Salk anything, this pandemic has only strengthened my of caution. In that sense, we were able to stay as well as a scientific perspective. scientists are highly collaborative and have expertise conviction of the power and importance of basic ahead of the curve and respond to events fairly in a broad range of research areas, many of which research to meet the greatest challenges of our time. quickly, well before California Governor Newsom’s are highly relevant for infectious diseases such as Inside Salk spoke with Hetzer on how As for Salk specifically, our strength lies in our people: stay-at-home order. This approach helped us to COVID-19. Several of our faculty are world experts the dedicated researchers and staff who, day in and he led the charge to shift research in not only pause or quickly end experiments where in using viruses to fight diseases or in understanding day out, strive to make the Institute a place “Where we could, but also, unfortunately, terminate other resistance and tolerance strategies that allow the face of continuing uncertainty, as cures begin.” I cannot predict when we will all be back experiments, as efficiently as possible. organisms to survive infections. Others work on well as what makes him hopeful about understanding the body’s immune response from on our beautiful campus again, doing critical research, Together with our Crisis Management Team, the various angles, which includes using metabolism to holding public events and enjoying one another’s Salk’s—and the world’s—future. faculty leadership as well as each lab worked hard slow infections; understanding how various immune company, but I am greatly looking forward to it.

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SUSAN KAECH

NEW COVID-19 RESEARCH COVID-19 EDITION In addition to Salk’s ongoing research areas relevant to COVID-19, several new 01 Professor Susan Kaech, who studies how we coronavirus-specific projects have recently launched. These innovative projects range from develop immunity to severe viral infections, such as understanding the structure of the virus to mobilizing the body’s immune reaction. influenza and now COVID-19, will collaborate with The Scripps Research Institute and La Jolla Institute to study the types of memory T and B cells that form in the lung following SARS-CoV-2 infection as a way to understand if and how long-term immunity can be established. This work will be critical to understanding the types of memory TONY HUNTER GERALD PAO T cells that COVID-19 vaccines will need to re-create in vaccinated individuals to establish benchmarks for 01 In severe COVID-19 cases, immune cells in the infected windpipe and lungs can release high levels of damaging generating protective immunity. 03 In a separate study, in collaboration with pulmonary inflammatory proteins called cytokines, colloquially known as physicians at UC San Diego and the VA hospital, Kaech a “cytokine storm.” American Cancer Society Professor Tony 02 Creating a protective coronavirus vaccine is will examine changes in the levels and composition of Hunter previously showed that the cytokine LIF (leukemia currently one of the world’s greatest challenges. Kaech surfactant in COVID-19 patients. Surfactant is a substance inhibitory factor) plays a role in pancreatic cancer. He will believes that immune cells called memory B and T cells in the lungs that allows us to breathe. The study will test whether cytokines, like LIF, play a role in the immune are likely critical for controlling the infection, and could compare surfactant levels with the health outcomes of overreaction seen in some COVID-19 patients. therefore be excellent targets for vaccines to enable long- COVID-19 patients to determine if a drop in surfactants is term immunity. Her lab, in collaboration with The Scripps associated with more severe disease. Her lab will also test Gerald Pao, a staff scientist in the Hunter lab, will work 02 Research Institute, will examine the role of memory T cells if genetic alterations in pathways that control surfactant with the Sanford Burnham Prebys Medical Discovery Institute inside the lungs during a COVID-19 infection. levels in the lungs alter the course of the disease. to generate a virus system that expresses a spike protein that mimics the ones on the coronavirus. The team will then examine the immune response to these spike proteins.

03 In collaboration with UC San Diego, USC and Sanford 04 Pao will also engineer CAR-T cells, cells that can Burnham Prebys Medical Discovery Institute, Pao will develop target specific proteins, to aid in the development of a a test to detect the presence of COVID-19 genomes in human coronavirus vaccine. These cells are repurposed from cancer nose and throat samples. He has designed this test, which will immunotherapy to provide immune surveillance and kill combine CRISPR with an imaging technology, so that it will only coronavirus-infected lung cells that have a spike protein on take a few minutes. their surface, early in the infection.

CLODAGH O’SHEA ALAN SAGHATELIAN JOSEPH NOEL

It will take a virus to kill a virus. Professors Clodagh O’Shea, Alan Saghatelian and Joseph Noel are exploiting the atomic structures of the SARS-CoV-2 virus, together with proprietary DMITRY LYUMKIS JUAN CARLOS IZPISUA BELMONTE synthetic virology and chemical biology platforms, to create transformative vaccines and gene therapies. Their pipeline 01 Assistant Professor Dmitry Lyumkis will examine the Professor Juan Carlos Izpisua Belmonte is collaborating with will target i) SARS-CoV-2 prevention by creating synthetic molecular mechanisms by which the non-structural protein a San Diego biotechnology company to develop COVID-19 live viral vaccines that induce broad and long-lasting NSP1 halts host protein production. This process ultimately treatments using nanoparticles. The researchers will use immunity and ii) SARS-CoV-2 treatment through viral gene helps the virus in promoting the production of its own viral RNA-targeting CRISPR-Cas technology to destroy the therapies that express synthetic nanoparticles that seek, proteins and the development of COVID-19. SARS-CoV-2 virus’ RNA. This treatment will prevent the virus neutralize and destroy SARS-CoV-2 and prevent pathology. from replicating in the body, thereby reducing the severity This research will uncover underlying principles and 02 The Lyumkis lab will also explore how the non- of an individual’s COVID-19 infection and limiting the virus’ overcome intractable clinical challenges, not just of SARS- structural protein NSP2 affects host cells during the chances of spreading. If successful, this approach could be CoV-2 today, but of SARS-CoV-3 tomorrow. development of COVID-19. extended to treat other RNA viruses in the future.

14 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 15 THANKTHANK YOUYOUZENITH ($100,000) Haeyoung Tang STAR ($5,000) While Symphony at Salk, our annual Ann Tsukamoto-Weissman and Joan and Irwin Jacobs Roberta and Stanley Bogen concert under the stars, will not take place Irv Weissman Corinne Mentzelopoulos, Sandrine Belanger and John Henry Felix this summer, the singular event will return Château Margaux AURORA ($15,000) Susanna and Michael Flaster August 21, 2021. It is guaranteed to be a Conrad Prebys Foundation BioMed Realty Eileen and Leonard Herman celebration of the power of Salk science Celgene Jenny Price and Tony Hunter GOLDEN SUN ($75,000) Cassandra and Fred Dotzler with our many valued supporters. Nancy McTigue and Jerry Joyce Karen and Don Cohn Debbie and Alan Gold Diana and Mark Knickrehm a concert under the stars Here is a list of 2020 Symphony at Salk Tina Simner Anne Daigle and Rich Heyman Evelyn and Ernest Rady sponsors and donors whom we would Fiona Mackin-Jha and Sanjay Jha Jane and Eric Sagerman SUPERNOVA ($50,000) UNDERWRITING GIFTS especially like to thank for their generosity Peggy and Ben Schapiro and support of Salk. The individuals and Martina and Dan Lewis Carl Hahn Shelley and Dave Odelson organizations recognized here have chosen Frederik Paulsen COMET ($10,000) SAVE THE DATE Ruth Warburg Cooley LLP to continue with their donations despite Suhaila White GALAXY ($25,000) AUGUST 21, 2021 this year’s cancellation. Natasha and David Dolby Jay and Sarah Flatley Karen Lane and Walter Eckhart Liz Keadle Karen and Michael Stone Family Foundation Carol and George Lattimer The Institute extends a special note of gratitude to Board Chair Dan Lewis for his Larry Jennings/Katherine Jennings Tori and Terry Rosen inspirational challenge to fellow sponsors to maintain their sponsorship of Symphony at Salk Family Office For more information, visit Mary Jane Salk despite its cancellation. Thermo Fisher Scientific www.salk.edu/symphony Darlene Marcos Shiley Marna and Tom Whittington or call (858) 967-4888 Science Continued Even as the Salk Institute shifts to tackling COVID-19 both institutionally and scientifically, it continues its groundbreaking research on other global problems facing humanity. In the following pages you will read about breakthrough discoveries that happened before and during the COVID-19 pandemic, and learn more about scientists who are pushing the boundaries in aging, cancer, plant science, neuroscience and many other areas.

18 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 19 A road map for ovarian health and aging Izpisua Belmonte’s lab published additional work uncovering how ovaries age in nonhuman primates in unprecedented detail. This road

Pictured are blastocyst-like map reveals several genes that could be used as structures (blastoids) biomarkers and could point to therapeutic targets from cultured cells for diagnosing and treating female infertility and

DISCOVERIES immunofluorescently stained UNLOCKING for the trophectoderm age-associated ovarian diseases, such as ovarian marker CDX2 (green) and the cancer, in humans. CELL SCIENCE inner cell mass marker SOX2 (red). The trophoectoderm 10/2019 10/2019 makes up the outer cells of THE BLACK BOX the blastoid.

OF EMBRYONIC Understanding early cell development After an egg is fertilized, cells begin to divide and form a blastocyst, a two-layered cluster of cells. The DEVELOPMENT way a blastocyst develops has implications for whether a pregnancy is successful, how organs form, and potentially CELL Little is known about the molecular even for diseases later in life, but studying blastocysts has 01/2020 been a challenge. Professor Juan Carlos Izpisua Belmonte and cellular events that occur during and colleagues created mouse blastocyst-like structures, early development of organs such dubbed “blastoids,” that had the same structure as natural Immunofluorescence analysis blastocysts, and offering a powerful new tool to advance of classic markers for smooth as the uterus, ovary and brain. Now, muscle cells in the ovary, research by circumventing the need for natural embryos. including muscle filaments research published by Salk labs (green), smooth muscle proteins (red) and nuclear DNA (blue). illuminates significant developmental The Izpisua Belmonte lab also wanted to study a critical processes for the first time, and milestone in development after the formation of the blastocyst: gastrulation. This stage occurs when an provides new methods to inform issues embryo transforms into a three-layered structure, from around pregnancy, infertility, and which all future tissues and organs will be derived. Izpisua Belmonte led an international team to uncover new insights View the full news reports developmental disorders such as autism READ and more discoveries online at into gastrulation by creating a method enabling primate spectrum disorder (ASD). www.salk.edu/news embryos to grow in the laboratory longer than ever before. The research, while done in nonhuman primate cells, could

Day 17 of a cultured primate embryo; the potentially inform approaches to regenerative medicines. various colors indicate markers of cellular differentiation (specialization).

20 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 21 DISCOVERIES

INFECTIOUS DISEASE

CELL STEM CELL 01/2020 “In previous structures, we learned about intasome biology, but here, we’ve really started to gain insight into the therapeutic angle of how drugs can target these important viral assemblies.”

DMITRY LYUMKIS

This illustration depicts the molecular structure of an HIV drug (at center) bound to an active site of the HIV intasome (surrounding structure), the viral machine that allows HIV to infect human immune Cells that will eventually become neurons (neural cells. By filling the binding pocket, the drug blocks the normal function of the machine, thereby progenitor cells) derived from individuals with preventing the virus from establishing an infection autism spectrum disorder (right panel) exhibit Team links rapid brain growth in the target cell. increased DNA damage (indicated by the red stain) compared to those derived from healthy in autism to DNA damage individuals (left panel). Research into the developing brain, led by Professor and Salk President Rusty Gage, first author Meiyan Wang and ADVANCES IN IMAGING TECHNIQUE AND PROGRESS IN colleagues, revealed a unique pattern of DNA damage SCIENCE BIOPHYSICS AND that arises in brain cells derived from individuals with a NEW INSIGHT INTO HOW HIV DRUGS 01/2020 MOLECULAR BIOLOGY macrocephalic form of autism spectrum disorder (ASD). WORK AT ATOMIC LEVEL 09/2019 They found that cells from people with this type of ASD not only proliferate more, but also naturally experience more Assistant Professor Dmitry Lyumkis’ team uses and optimizes an advanced replication stress, spurring DNA damage. The observation imaging technique called cryo-electron microscopy (cryo-EM) to visualize helps explain what might go awry in the brain during cell large protein complexes within cells and to uncover how these structures division and development to cause the disorder. work. In the fall, Lyumkis and Philip Baldwin co-authored a study that provides a foundation for quantitatively determining how differences in viewing angles affect the resulting 3D structures of proteins. Then, in January, Lyumkis, Salk co-first author Dario Passos and colleagues reported on how a powerful class of HIV drugs binds to a key piece of HIV machinery. By resolving this complex in 3D for the first time while different drugs were

attached, the researchers discovered structural reasons for why these From left: Dario Oliveira Passos, therapies are so potent. Dmitry Lyumkis and Ilona K. Jó´zwik

22 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 23 DISCOVERIES

NEUROSCIENCE + NEUROSCIENCE METABOLISM

ALTERED POTASSIUM LEVELS BIOLOGICAL PSYCHIATRY CIRCADIAN CYCLES CAN IN NEURONS MAY CAUSE MOOD 10/2019 & BENEFIT OUR HEALTH SWINGS IN BIPOLAR DISORDER 02/2020 Professor Satchin Panda studies circadian People with bipolar disorder experience dramatic shifts in mood, clocks, the internal programs that mediate our oscillating between often debilitating periods of mania and depression. daily biological rhythms and affect our health. Now, a sweeping new set of findings by Professor and Salk President Rusty In two recent papers, Panda and his team Gage, first author Shani Stern and colleagues has revealed previously examined how the body sets these clocks, while unknown details about why some neurons in bipolar patients swing a third paper reveals what these rhythms can between being over- or underexcited. In two recent papers, the team mean for our well-being. used experimental and computational techniques to describe variations in potassium and sodium levels in brain cells derived from people with In the first paper, Panda and colleagues reported Healthy CA3 pyramidal neurons bipolar disorder, which may help to further explain why one-third of stained to show the cell body (blue) a novel technique for determining how neurons patients respond to lithium and the rest do not. and axons (green). communicate, which was employed in mice to uncover details about how the brain responds to light signals received by the retina. In the second study, Panda, Salk first author Ludovic Mure and colleagues reported the discovery of three cell NEW INSIGHTS BRAIN BIOMARKER PREDICTS types in the eye that detect light and align the INTO HOW COMPULSIVE DRINKING brain’s circadian rhythm to ambient light. ELIFE GENES CONTROL 04/2020 In the third paper, Panda, Salk first author SCIENCE 11/2019 Emily Manoogian and colleagues described COURTSHIP AND their clinical study of eating schedules based AGGRESSION on circadian rhythms. They found that a 10- Fruit flies, like many animals, engage in a variety Nuclei (blue) of the hour time-restricted eating intervention, when medial prefrontal cortex combined with traditional medications, resulted of courtship and fighting behaviors. Assistant neurons projecting their Professor Kenta Asahina and co-first authors axons (green) to the in a variety of health benefits for participants periaqueductal gray area. with metabolic syndrome, including weight loss, Kenichi Ishii and Margot Wohl have uncovered reduced abdominal fat, lower blood pressure the molecular mechanisms by which two sex- determining genes affect fruit fly behavior. The and cholesterol, and more stable blood sugar and Although alcohol use is ubiquitous in modern male flies’ courtship and aggression behaviors, insulin levels. This pilot study could lead to a society, only a portion of individuals develop alcohol they showed, are mediated by two distinct genetic new treatment option for patients who are at risk use disorders or addiction. Yet, scientists have not programs. The findings, both published ineLife , for developing life-altering and costly medical understood why some individuals are prone to developing demonstrate the complexity of the link between conditions such as diabetes. From left: Satchin Panda, Emily Manoogian and Ludovic Mure. drinking problems, while others are not. Professor Kay sex and behavior. Tye and colleagues have discovered a brain circuit that controls alcohol drinking behavior in mice. The findings suggest a biomarker for predicting the development of CELL CELL SCIENCE www.salk.edu/panda202005 compulsive drinking and may pave the way for a better REPORTS METABOLISM 12/2019 WATCH 10/2019 12/2019 understanding of human binge drinking and addiction.

Researchers studied how sex-determining genes affect neurons known to control courtship (shown in orange on the left) and WATCH www.salk.edu/tye202005 aggression (shown in blue on the right) in fly brains.

24 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 25 DISCOVERIES

METABOLISM CANCER

EAT LESS, LIVE LONGER MITOCHONDRIA ARE THE “CANARY IN THE If you want to reduce levels of inflammation throughout CELL COAL MINE” FOR 02/2020 your body, delay the onset of age-related diseases CELLULAR STRESS and live longer—eat less Mitochondria, tiny structures present in most food. That’s the conclusion of a new study cells, are known for their energy-generating led by a collaborative group of scientists, machinery. Professor Gerald Shadel, first author including Salk Professor Juan Carlos Zheng Wu and colleagues have discovered a new Izpisua Belmonte, that provides the most function of mitochondria: they set off molecular detailed report to date of the cellular effects The illustration represents the ways in which caloric restriction affects various alarms when cells are exposed to stress or of a calorie-restricted diet in rats. While aspects of cellular function, with the overall result of reducing inflammation and to chemicals that can damage DNA, such as the benefits of caloric restriction have long the activity of many aging-related genes. been known, the new results show how this chemotherapy. The results could lead to new restriction can protect against aging in cancer treatments that prevent tumors from WATCH www.salk.edu/belmonte202005 cellular pathways. becoming resistant to chemotherapy. Pictured are mitochondria (red), cell nuclei NATURE (blue) and mtDNA (white dots). METABOLISM 12/2019

PROTEIN INTERACTIONS

MYSTERIOUS TUFT CELLS FOUND FRONTIERS Roughly 25,000 genes code for to mitigating cell stress. In the IN PHYSIOLOGY 04/2020 biologically relevant proteins, most second study, published in December, TO PLAY ROLE IN PANCREATITIS MICROPROTEINS of which are large chains of 300 Saghatelian and first author Thomas HAVE MAJOR or more linked amino acids. But, Martinez identified over 2,000 The function of tuft cells—cells sensitive to chemical changes—in increasingly, “microproteins,” with new, small genes that may encode the pancreas has largely remained a mystery. Now, Professor IMPLICATIONS FOR fewer than 100 amino acids, are for microproteins—expanding Geoffrey Wahl, co-first authors Kathleen DelGiorno and Razia HUMAN DISEASE being found to have important roles the number of human genes by 10 Naeem, and colleagues have uncovered how tuft cells form in health and disease. percent. Both publications provide during pancreatic inflammation as well as their surprising role in a better understanding of human immunity, using mouse models of pancreatitis. The findings could In a study published in October, biology that may eventually have NATURE lead to the development of new biomarkers to test for pancreatitis NATURE CHEMICAL Professor Alan Saghatelian, implications for diseases ranging COMMUNICATIONS BIOLOGY co-corresponding author Uri from cancer to diabetes. and pancreatic cancer. 10/2019 12/2019 Manor, first author Qian Chu

and colleagues showed that the WATCH www.salk.edu/saghatelian202005 microprotein PIGBOS contributes Pancreatitis tuft cells (red, microvilli and actin rootlets) in the injured pancreas (green); nuclei (blue) The “microproteins” encoded by smORFs have been linked to immune function, cell stress and From left: Geoffrey Wahl, Kathleen many other cellular processes, DelGiorno and Razia Naeem which suggests that detecting smORFs could lead scientists to new biomarkers and drug targets for human diseases.

26 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 27 DISCOVERIES

PLANT BIOLOGY AGING

HOW PLANTS SOUND NATURE PLANTS ALZHEIMER’S DRUG THE ALARM ABOUT 03/2020 CANDIDATES REVERSE eLIFE DANGER 12/2019 BROADER AGING,

One role of plant hormones is to perceive trouble—whether STUDY SHOWS an insect attack, drought or intense heat or cold—and then Scientists from the lab of Professor David Schubert, signal to the rest of the plant to respond. Now, Professor including first author Antonio Currais and co- Joseph Ecker, Salk co-first author Mark Zander and corresponding author Pamela Maher, have shown how the collaborators report new details about how plants respond Alzheimer’s drug candidates CMS121 and J147 can slow The top left image shows a knee joint in a healthy rat. (Red [surrounding white] indicates cartilage.) Bottom left image to a hormone called jasmonic acid, or jasmonate. The aging in healthy older mice, blocking the damage to brain shows a joint with grade 2 untreated osteoarthritis. Top right findings reveal a complex communication network and cells that normally occurs during aging and restoring image shows a joint with osteoarthritis that has worsened from grade 2 to grade 4 after six weeks of placebo therapy. could help members of Salk’s Harnessing Plants Initiative the levels of specific molecules to those seen in younger The bottom right image shows a joint with osteoarthritis that develop crops that are hardier and more able to withstand brains. The research points out a new pathway that links improved from grade 2 to grade 1 (mild) after six weeks of combination therapy with alphaKlotho and sTGFbR2. rapid climate change. Arabidopsis thaliana, a small flowering plant normal aging to Alzheimer’s disease. in the mustard family.

DIABETES DRUG HAS

GENETICS UNEXPECTED, BROAD IMPLICATIONS FOR HEALTHY AGING Metformin is the most commonly prescribed type 2 From left: Juan Carlos Izpisua Belmonte, Paloma Martinez- Redondo, Isabel Guillen-Guillen and Pradeep Reddy. diabetes drug, yet scientists still do not fully know how EXPERIMENTAL DRUG it works to control blood sugar levels. Professor Reuben JOURNAL OF BOOSTS LEVELS OF BIOLOGICAL Shaw, director of Salk’s NCI-designated Cancer Center, CHEMISTRY and collaborators have used a novel technology to DRUG COMBO 05/2020 PROTEIN GOOD FATS investigate why it functions so well. The findings, which REVERSES & CELL identified a surprising number of biochemical “switches” 01/2020 Professor Alan Saghatelian, first author Meriç for various cellular processes, could also explain why ARTHRITIS IN RATS Erikci Ertunc and a collaborative team of scientists metformin has been shown in recent studies to extend People with osteoarthritis, or “wear and have identified two genes that can regulate levels health span and life span. tear” arthritis, have limited treatment of healthy fats called FAHFAs, in mice. Because From left: Justin Wang, Alan Saghatelian and Meriç Erikci Ertunc. options: pain relievers or joint replacement FAHFAs decrease inflammation and increase insulin surgery. Research co-led by Professor Juan sensitivity, a better understanding of the activity of Carlos Izpisua Belmonte and Salk co-first their regulatory genes may eventually lead to therapies authors Paloma Martinez-Redondo and for people with diabetes and inflammation. They CELL Isabel Guillen-Guillen, has discovered that a found that the loss of the genes led to higher-than- REPORTS 12/2019 powerful combination of two experimental normal levels of the beneficial FAHFAs, while blocking drugs reverses the cellular and molecular signs the genes’ activity with an experimental drug also Computational analysis revealing of osteoarthritis in rats as well as in isolated increased FAHFA levels. targets of metformin. human cartilage cells.

28 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 29 30 INSIDE SALK IN THE NEWS SUMMER 2020 DIVERSITY infections); andmuchmore. (thus puttingtheirresidentsatgreaterriskforpooroutcomesfrom considered essential;whichcommunitieshavegreaterairpollution society. Theseincludewhohasaccesstohealthcare;whoseworkis life, andlayingbaremanyofthedeep,structuralinequitiesour The COVID-19pandemicisaffectingeverydimensionofAmerican AND UPDATE ON INITIATIVES TO SUPPORT Salk’s missiontobetterhumanityextendsbeyondscience. The InstitutestandswithBIPoCatSalkandeverywhere, Adding tothecollectivetraumaisracismandracial not onlyinthespiritofsolidarity, butalsowithactions injustice beingexperiencedbycommunitiesofBlack, humanity andleadtomeaningfulchange.Repugnant

that willcontinuetocontributethebetterment of people aredevastatingremindersthatindividuals, institutions andcommunitiesmusturgently racial discriminationandviolenceagainstBlack Indigenous andotherpeopleofcolor(BIPoC). BIPOC continually assessandenhanceefforts WWW.SALK.EDU to change.

WWW.SALK.EDU • • • • working onseveralinitiativestothisend: Salk’s leadershipandtheInstitute’s OfficeofEquityandInclusionhavebeen CAMPUS CLIMATE SURVEY MISSION STATEMENT ANDCOREVALUES MANDATORY EDUCATION ANDTRAINING DIVERSITY &INCLUSIONTASK FORCE resources forall;anddetermineswhetherthecampus backgrounds andperspectives;providesaccess all membersoftheInstitute;seeksdiversityinindividual environment thatwelcomesandenablesparticipationby survey thatwillassesstheextenttowhichSalkprovidesan Committee, theInstituteisdevelopingacampus-wide At therecommendationofCampusCultureAdvisory Salk does. guide ourprogress,theymustbeembodiedineverything of diversityandinclusion.Forthosevaluestoendure adamant initsoppositiontoracismandstalwartsupport the inspiringlegacyoffounderJonasSalk,Instituteis articulated corevalueswillbedocumented.Asstewardsof Salk’s missionstatementwillberefinedandasetofclearly and empoweredtoassistothersinneed. The trainingalsoprovidestoolstohelppeoplebeproactive implicit bias,privilege,andbystander-to-upstander guidance. training thatwillrolloutinJuly2020,focusingonexplicitand In late2019,theInstitutebegandevelopingmandatory racism andinjustice. of identifyingwaysinwhichtheInstitutecanfightsystemic and inclusionofBIPoCatSalk,withanimmediatecharge staff, theTask Forcewillfocusonincreasingthediversity and parityinscience.Working inconcertwithfacultyand been activethroughouttheircareersinpromotingdiversity Dannielle EngleandProfessorKayTye, bothofwhomhave established. Itisbeingco-chairedbyAssistantProfessor and InclusionTask Force,whichhasnowbeenformally in 2019,theInstitutecommittedtocreatingaDiversity When theCampusCultureAdvisoryCommitteewasformed

• • INCREASED COMMUNICATIONS DISCUSSION SESSIONS fronts. awareness onissuesofequityandinclusionmultiple communications tohelpbolstereducationandraise The Institutewillprovideexpandedandenhanced offer theopportunitytoengageinconstructivedialogue. community. Theseeffortsaimtoamplifydiversevoicesand called “CollectiveVoices forCommunityHealing,”theSalk pertaining toequityandinclusionaswelldiscussionsessions, OEI launchedaquarterlydiscussionclubaboutissues a diverseandinclusiveenvironment. can beimplementedtofurtherSalk’s commitmenttopromote campus culture.Theresultswillhelpinformmeasuresthat is experiencingthevaluesweespousewhenarticulating has avoice,atSalkandbeyond. and research,ensurethateveryone support diversityinourpeople,ideas racism andinjustice,continuetoactively we mustbevigilantinhelpingtoend in thesechallengingtimes,thismeans “the humandimension.”Particularly side ofnature—whathereferredtoas merely withnature,butthehuman institution thatwouldbeconcernednot ancestors.”He soughttofoundan greatest responsibilityistobegood Jonas Salknotablysaid,“our

INSIDE SALK SUMMER 2020 31 32 INSIDE SALK OBSERVATIONS SUMMER 2020 WWW.SALK.EDU AZIM EIMAN WWW.SALK.EDU Humans can move bodies their to can Humans DECODING DEXTERITY DECODING the nervous system is able is orchestrate to nervous system the yet scientists still tasks, dexterous these contraction the of coordinate dozensto rest ofrest even us, movements everyday such acts of astonishing complexity. of astonishing acts We need are email an or typing ashirt buttoning as do incredible things. Some can play Somedo incredible can things. do not have a clear understanding of howdo not understanding have aclear concertos orconcertos hit but home for runs, the of muscles precision with accomplish to such complex behaviors. thoughts onthoughts what’s neuroscience, in next how all chatted with Azim to learn about his learn to Azim with chatted Salk Inside scientists are philosophersscientists what are he learned and about movement newborn. his from observing Laboratory and the William William the and Laboratory professor assistant Azim, Eiman fingers. By using sophisticated sophisticated using By fingers. Scandling Developmental Chair, Chair, Developmental Scandling create movement, and how the how the and movement, create in the Molecular Neurobiology Neurobiology Molecular the in affected by neurodegenerative neurodegenerative by affected the in how circuits uncovering is dexterous control cord spinal and disease and injury. injury. and disease function of these pathways is is pathways of these function nervous system work together to to work together system nervous lab his tools, genetic molecular and hands arms, movement of the seeks to uncover how the brain brain how the uncover to seeks INSIDE SALK

SUMMER 2020 33

“Molecular genetics allows us to disentangle What big questions are you trying to answer in to control movement. The first is the chain of events that sends the brain with surgical science? commands from your brain down to your spinal cord, and ultimately out to your muscles to move. The second pathway EA: We’re trying to understand how the brain controls precision, so we can now behavior. Asking these types of questions is like trying to solve involves all of the feedback from your body (such as your skin finally uncover each a large puzzle where we have to figure out how all the pieces fit and your muscles) that gets sent back into your spinal cord together, often without even knowing what all the pieces are. and brain to report the consequences of the movement. These type of neuron’s role and And not just how they fit together in a static picture, but how command and sensory pathways are constantly interacting function in movement. ” they dynamically change with time as well. For example, as you in a dynamic way, and we are trying to define how these EIMAN AZIM reach down to tie your shoe, how does the communication of interactions take place and why they are needed for dexterity. different neural circuits change to coordinate behaviors? If you stumble, how do the circuits respond so you don’t fall? One of the specific projects in my lab right now is examining how to control the strength of the sensory feedback My lab tries to gain insight on how the brain processes transmitted to the brain. Our bodies are bombarded with What brought you to Salk and what keeps you Since you study how the nervous system signals to produce a desired outcome, and what goes wrong in stimuli that activate sensory receptors. Much of this sensory conditions that affect movement, such as Parkinson’s disease here? controls movement, are you excited to watch information is distracting or noisy, suggesting that we need and amyotrophic lateral sclerosis (ALS). I believe that if your son reach developmental milestones such a way to “turn down” some of these signals, while allowing EA: The Salk Institute is different than any other institution we want to develop better approaches to diagnose and treat as crawling and walking? the important signals to make it into the brain. We’ve been I was considering. It’s small by design and incredibly disease and injury, we need a much better understanding of identifying circuits in the brain that can adjust the strength of collaborative. There are no departments and very few barriers EA: Oh, absolutely. It’s been fascinating. When he rolled how the normal system fundamentally operates. tactile signals that come from our skin, a process that appears or boundaries between disciplines. When you’re walking for the first time, it was just amazing to watch. Babies are to be critical for effectively grasping and manipulating objects through the beautiful campus, you run into some of the best experimentalists; they try something and then it works or produces an outcome, and they do it again and again to Neuroscience is an established field. Why do to interact with the world. scientists in the world. For example, I might have coffee with confirm that it’s true. And if something fails, they’ll go and try scientists still know so little about how the a plant biologist one day and a cancer scientist the next. That something new. These are good lessons for the lab. brain controls movement? Growing up, did you always know you wanted doesn’t happen quite as easily at big universities. to become a neuroscientist? EA: The human brain contains nearly 100 billion neurons What do you think the future holds for with a huge variety of cell subtypes, all intermingled in What are some of your favorite things to do EA: I have always loved science, but it really wasn’t until understanding the neural basis of movement? incredibly complex networks. Trying to disentangle these college that I fell in love with neuroscience. When I was at outside of work? networks to decipher the function of each type of neuron is EA: We’re at a fascinating and fast-changing moment in Stanford University as an undergraduate, I was passionate EA: I play the guitar. I really enjoyed playing in a band difficult. Over the past few decades, there’s been a molecular neuroscience. The field of movement research is already about philosophy, specifically philosophy of mind. As I in college, and I recorded an album while I was doing my genetic revolution in neuroscience. What this means is that gaining insights that are telling us how our nervous system dove deeper into the subject, I became fascinated with the postdoctoral fellowship in New York. I have yet to find the time we can now take advantage of the fact that different types of might be working, and also showing us what might go wrong questions, which were grand, but a bit frustrated with our cells, including neurons, express different genes. These diverse or the bandmates here in San Diego, so it’s on the back burner in disease and injury. For example, the development of inability to come up with definitive answers. gene expression patterns allow us to differentiate between for now. One of the reasons time is scarce is that my wife and I prosthetics that receive signals from and send signals to the different types of neurons, and to use their genetic identities recently had our first child, which has been pretty incredible. brain is moving at an incredible pace, helping people that And so that’s when I decided to enter laboratory science to to access them selectively in our experiments. So, if we can have lost motor function. The way we can continue to develop perform experiments and collect data on accessible problems decipher these molecular codes, then we can look at how these What is it like having a baby while being a full- advanced technologies like these is by using the lessons we’ve in the brain that could eventually shine some light on these neurons connect to each other to form circuits. We can also time research scientist? learned in basic science laboratories, and for scientists to larger questions about the human condition. remove specific neurons from the circuit, or turn them on or off continue to learn lessons from the patients who can benefit. EA: I’m still figuring that out, but it’s a balancing act. Before at will, to investigate their function. Molecular genetics gives This two-way communication between experiments in the lab having my son, my friend gave me the following advice: “You us the tools to access the brain with precision, so we can ask Do you think your background in philosophy and patients in the clinic inspires me every day. targeted questions about each type of neuron’s contribution to informed your current career in research? basically have to get the same amount done in a lot less time.” And he was not wrong. So, I’ve tried to cut out a lot of the movement. EA: I do. I think philosophy teaches us how to think about a extraneous stuff in my life to better focus on the science when problem. We’re all philosophers; scientists gain their training I’m at work, and my son while I’m at home. LISTEN www.salk.edu/podcast/eiman-azim Do you have any exciting projects in your lab by earning a doctorate in philosophy. The life sciences have right now? long been a branch of philosophy, where we look at the world, EA: I find them all exciting! Big picture, we’re interested in are curious about a problem, and try to come up with rational Is sleep considered extraneous? learning more about how two major types of pathways interact and intelligent ways to address that problem. EA: Often.

34 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 35 36 Institute forBiologicalStudies Credit: LeoAndradeandUriManor, Salk in responsetosound. hair-like structuresthatvibratebackandforth and inner(yellow)haircells,namedfortheir of theinnerear, includingtheouter(green) sensory tissueinthecochlea,spiralcavity A scanningelectronmicroscopeimageof INSIDE SALK LISTEN RESOLUTION SUMMER 2020 www.salk.edu/podcast/uri-manor 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 NGS Core director. Now, Hah’s main goal is to

DAY-TO-DAY make the NGS Core accessible to the entire Salk Salk’s NGS Core houses state-of-the-art equipment community. to allow scientists to examine genetic codes. As INSIGHTS the director of the NGS Core, Hah collaborates with LEISURE TIME everyone from plant biologists to neuroscientists to provide support and information about sequencing Hah loves spending time outdoors and recently genes and entire genomes. On any given day, she went skydiving for the first time. “It was amazing From bacteria to humans, every living organism may explain differences in techniques, provide to jump from a plane and feel gravity pull me back has a unique genetic code in the form of DNA, a hands-on training and review experimental design. towards the earth,” she says. “The sun was setting over the ocean, and it was just so beautiful. I was sequence of four letters that spell out instructions uncontrollably laughing with happiness the entire

for the organism’s genes to follow. Using a technology PATH TO SALK time.” Hah was studying the humanities in high school called next-generation DNA sequencing, scientists She also has a passion for orchids and last year when she first read about the Human Genome trekked along the Inca Trail, in Peru, searching can get a readout of those instructions, allowing them Project, a $2.7 billion venture that represented for exotic blooms. She counted nearly 25 the first complete catalog of the human genome, to answer important biological questions about gene different species during her trip, including the the DNA sequences that make up our 23 pairs function in health and disease. mountain-growing Brachtia andina, with its vibrant, of chromosomes. The project armed scientists long-lasting, yellow-orange flowers. She looks with a genetic map that enabled them to start forward to exploring the renowned Orchid House at Staff Scientist Nasun Hah can vividly exploring related questions about topics such as the San Diego Zoo in the near future. remember using this technology for the first the function of each gene. Blown away by the time, during graduate school, to examine subtle biological differences that helped explain human complexity, Hah immediately signed INSPIRATION gene expression. It was expensive and up for her first biology class. “I was always so “So much of biology is hard to prove. It’s took more than a week to receive intimidated by science until I learned that it complicated and intricate, yet it somehow comes the results, but she was elated—and was logical and filled with patterns that I could together in the most sophisticated way,” says Hah. decipher,” says Hah. hooked. Hah is now the director of the “Uncovering these connections is fascinating and Hah studied biochemistry at Yonsei University, in reminds me of the importance of basic science.” Next Generation Sequencing (NGS) South Korea, and later attended graduate school Hah also finds inspiration in discussing ideas with Core at Salk, where an entire genome at Cornell University, where she examined how other scientists; even casual conversations at Salk’s estrogen could directly and immediately alter coffee cart can be a catalyst for an innovative containing over 20,000 protein-coding gene expression, and how genetic errors could research project. genes can be sequenced in a single day. result in breast cancer. She also investigated “The amount of data and knowledge transcription regulation, the process of creating FUN FACT an RNA copy from a DNA template, as well as Although Hah is originally from South Korea, she we can receive from sequencing nuclear receptors, which drew her to the work has spent large portions of her life living in the technology is immense,” says Hah, of Professor Ronald Evans at Salk. Evans’ lab Netherlands, Japan and the United States. Her discovered nuclear receptors, a large family then laughs. “And this technology father worked as an executive for an airline of molecules that respond to various steroid company, so his role required the family to relocate keeps getting better and better, so I hormones such as estrogen, which are now to countries with entirely different languages and primary targets in the treatment of cancers, can never leave the field!” cultures. Due to her diverse upbringing, Hah values osteoporosis and asthma. being open-minded and enjoys working with “Evans’ work came up a lot as I wrote my people from all backgrounds. dissertation; he was my scientific hero,” says Hah. “So, by the time I was finishing my PhD, I knew I wanted to work with him.” LONG VIEW Sequencing technologies have evolved over During her postdoctoral fellowship in Evans’ lab, time, zooming in from the entire genome and Hah researched how potent anti-inflammatory homing in on other categories of information, drugs suppressed inflammatory messengers such as variations of gene expression in each cell. Nasun Hah sent by genes. She was fascinated by a still “Sequencing technologies are improving all the unresolved scientific paradox: how can certain Director of the Next Generation Sequencing Core time,” says Hah. “In the future, I think we will see a receptors activate some genes yet repress shift towards single-cell sequencing and capturing others? She also examined the role of gene spatial information such as where genes are located expression in acute inflammation and used a in a given organ or tissue. This spatial information variety of genomic approaches to dissect the could aid scientists in defining detailed molecular inflammatory signaling. maps for each cell type in diverse tissues. Genomic Near the end of her fellowship, Hah decided sequencing is going to get more complicated, but she wanted to focus on cutting-edge, next- it’s also going to be more exciting.” generation sequencing and took on the role of

38 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SPRING 2020 39 A spotlight illuminates a young woman, “Science outreach is the thing that keeps me going,” Matty positioned center stage, wearing red-framed says. “When I can break science findings down into analogies glasses. She grips the microphone, readying and fun vignettes for people to understand, that’s when I get inspired to go back into the lab and do the work.” herself for the next cue. The judge declares that the subject is…SCIENCE. Recently, Matty visited a kindergarten class at a local elementary school, where she guided the students through “Whenever I see my worms wiggle across the plate, I know I the examination of worms under a microscope. She asked the should study their movement—it’s a ‘sine’!” says the performer, students what they thought they had in common with a worm. Molly Matty. The audience laughs, appreciative of her pun Many students pointed out that “both worms and people alluding to the serpentine motion of worms as sine waves. poop.” Amused, Matty explained that another similarity is that Pun competitions draw sold-out crowds. The rules are simple: nematodes have neurons that make up a series of connections following the given theme, make a pun within 10 seconds similar to those of a human brain. That makes them ideal or you’re out. Only one person will remain to become the models in the study of neural circuitry related to emotion and Pun Master. other factors. “Every kid should know that being a scientist is a career they NEXT GEN Outside of punning, Matty spends her time as a postdoctoral researcher, studying the nematode Caenorhabditis elegans can have. Scientists can look, talk and be like them,” Matty in the lab of Associate Professor Shrek Chalasani. Punsters says. “Many of us deal with imposter syndrome as adults. I like may appreciate that the name is pronounced “see elegance.” to remind people: just remember, you belong here.’” Indeed, although these tiny worms are only half an eyelash She also likes to share science through what she calls “Uber in length, their transparent bodies allow scientists to outreach.” Every time she takes a ride-hailing service, such view the worms’ inner workings, making them an elegant as Uber, she model organism for research. In fact, Matty’s research incorporates involves observing the worms as they consume their science into the favorite food: bacteria. “Science outreach conversation. Similar to the human gut, the C. elegans gut is in regular On one trip, she is the thing that communication with the rest of its body, including its nervous shared with her system. Matty wants to know how ingested bacteria integrate driver that she keeps me going.” into the worm’s gut microbiome to affect this communication. studies how the microbiome affects “If different bacteria can alter the gut microbiome, then could behavior. He happened to be studying nutrition at a local they also affect behavior through this chain of signaling to the college and was immediately intrigued. The car ride turned What Worms brain?” Matty asks. into an open forum of questions.

Can Teach Us Understanding how bacteria affect the brain and behavior “I enjoy doing ‘Uber outreach’ because it breaks down barriers. could provide insights into human conditions such as anxiety It allows members of my community to feel empowered to ask and depression. These disorders may be affected, and possibly a question that they’ve always been afraid to ask,” Matty says. improved, by ingesting certain bacteria. In fact, the gut- “And it gives me a chance to practice explaining things that behavior field is growing as more and more studies suggest a I’ve maybe never had to explain before.” MOLLY connection between food and mood. Outside of her science and outreach efforts, Matty enjoys Matty shares that C. elegans makes an ideal model for running. Every year, she runs her age in kilometers to MAT T Y studying this connection for a few reasons: the environment celebrate her birthday. Since moving to San Diego, Matty has (a petri dish) can be perfectly replicated, the worms self- embraced the Southern California lifestyle; she has learned fertilize to produce genetically similar offspring, and the to surf and regularly practices yoga at one of the local studios. microbes that they ingest are closely monitored. These factors She also practices her puns for competition. allow for exceptionally controlled experiments that would be impossible in most other species. “I hope talking about my microbiome project didn’t ‘bug’ you too much,” Matty says, laughing. Matty not only brings her humor and passion for science to the public through being punny but also by volunteering with www.salk.edu/podcast/molly-matty Salk’s Education Outreach Program.

40 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 41 42 INSIDE SALK SPOTLIGHT SUMMER 2020 deep orshallow inthesoil. discovered agene that determines whetheraroot grows plants thrive instressful environments. Priortohe that, Recently, Busch uncovered agene responsible for helping SALK PRESIDENT RUSTY GAGE broad and positive impact at Salk.” and computational skills are having a biology research, his general leadership In addition to his contributions to plant to address climate change using plants. an invaluable asset to the Institute’s effort functions and genetics of plant roots are “Wolfgang’s keen insights into the plant root growth. molecular, cellularandphysiological networks to shape interacts withtheenvironment andistranslated by mechanisms determine how aplant’s genetic information research seeks to understand whichgenes andmolecular for obtaining water andnutrients from thesoil. His Laboratory, studiesplants’ roots, whichare critical Biology Laboratory andtheIntegrative Biology Busch, amember ofthePlant Molecular andCellular Trustees. by President Rusty Gage andtheInstitute’s Board of by Salkfaculty andnonresident fellows, and approved biology. Thepromotion was based onrecommendations rank ofprofessor for hisnotablecontributions to plant The SalkInstitute haspromoted Wolfgang Busch to the PROFESSOR TO PROMOTED WOLFGANG BUSCH

functioning GSNORgene(right). gene (left) growbetter withhighironlevelsthanplants withoutthe and rootgrowth.Plants( for highirontoleranceinplants.Irontoxicity leadstoimpairedleaf Busch recentlydiscovered theGSNORgene. The geneisrequired Arabidopsis thaliana Arabidopsis WWW.SALK.EDU ) withthefunctional Wolfgang Busch WWW.SALK.EDU says Chory. success ofHPIprograms to fight climate change,” set ingenomes ofplants willcontribute enormouslyto the creative scientist ofthehighestintegrity. Hisuniqueskill “We are elated that we couldrecruit Todd, whoisa to thefaculty. was created bySalkin2018to attract andretain top talent Joanne Chory. Thenon-tenured research professor track research at Salkin2007 underthedirection ofProfessor Initiative (HPI).Michaelcompleted hispostdoctoral provide key expertise ingenomics to theHarnessing Plants where hewilloversee hisown research group aswell as in thePlant Molecular andCellular Biology Laboratory, Todd Michaelwillreturn to Salkasaresearch professor AS ARESEARCH PROFESSOR MICHAEL JOINS SALK FACULTY TODD GENETICIST PLANT Todd Michael Institute ofRutgers University. at Monsanto; andassistant professor at theWaksman Abbott Laboratories; headoftheGenomeAnalysis Center heheldpositionsincludingdirectorthat, ofGenomicsat Venter Institute, fewer thantwo milesfrom Salk.Priorto as professor anddirector ofInformatics at theJ. Craig from theUniversity ofVirginia. He previously served biology from DartmouthCollege andhisBAinbiology Michael received hisPhDinmolecularandcellular enables advanced breeding for next-generation crops. were conserved byevolution across higherplants, which They found that thetime-of-day gene-expression networks such asdailylight-dark cycles aswell asseasonal changes. enables plants to anticipate changes intheirenvironment to provide molecularevidence that thecircadian clock His group also used themodelplant Arabidopsis thaliana new sequencing technologies andgenome analysis tools. that can survive extreme drought,bypioneering theuse of plant genome ofOropetium thomaeum,atype ofgrass Michael previously publishedthefirst near-complete deeper rooting. genetic architecture controlling specifictraits, suchas ground. Inparticular, histeam willbeinvestigating the excess amounts ofatmospheric carbon deepinthe with deep, robust root systems capable ofstoring sequencing supportto create SalkIdeal Plants population. Hisresearch group willprovide genome while providing more food, fuelandfiber for agrowing in order to mitigate thedisastrous effects ofclimate change efforts to optimize aplant’s natural ability to store carbon As partoftheHPIleadership team, Michaelwillhelp INSIDE SALK SUMMER 2020 TM , plants 43 SPOTLIGHT

plant biology and more,” says Salk Institute President Rusty Gage. “We simply could not make the life-changing SALK BOARD discoveries Salk is known for without our supporters.”

WELCOMES Charity Navigator’s data-driven analysis of the 1.5 million NEW TRUSTEES American charities has been covered by Forbes, Business Week and others for providing donors with a way to LARRY JENNINGS, JR., recognize nonprofits that provide greater accountability, AND TIMOTHY transparency and concrete results. SCHOEN “Our donors supported Salk science in record fashion the past fiscal year, and I believe one of the significant reasons

Larry Jennings, Jr. for that is the confidence they have in the Institute’s In January, the Salk Board of INSTITUTE RECEIVES stewardship,” says Rebecca Newman, Salk’s vice president of External Relations. “We are honored to be included in Trustees welcomed two new Jennings is co-founder and senior 1995 to 2001. He is a member of CHARITY NAVIGATOR’S managing director of ValStone the board of trustees of Carnegie such elite company.” trustees, Larry Jennings, Jr., a Partners, where for 20 years he Mellon University; chairman of the HIGHEST RATING The Institute continues to make bold progress in pursuing has co-led the company’s strategic Morgan State University Foundation private equity and municipal ambitious solutions to the difficult challenges facing direction, investment decisions Investment Committee; and board FOR NINTH humanity, including climate change, aging and cancer. finance expert, and Timothy and investor relations. From 1987 chair of the Baltimore Municipal Schoen, a real estate and to 1994, Jennings was co-head of Golf Corporation. He earned a BS CONSECUTIVE TIME “I wish to congratulate the Salk Institute for Biological the Legg Mason public finance in mathematics and economics and corporate finance executive. Salk executes consistent best Studies on attaining the coveted 4-star rating nine investment banking department. an MS in industrial administration consecutive times, demonstrating strong financial health He also founded and served as CEO (MBA), both from Carnegie Mellon financial practices and commitment to accountability and transparency,” says of Carnegie Morgan Partners from University. Michael Thatcher, president and CEO of Charity Navigator. For the ninth consecutive time, the Salk Institute has earned the highest ranking—4 out of 4 stars—from Charity Navigator, Since 2002, Charity Navigator has used objective analysis America’s largest independent charity and nonprofit evaluator. to award only the most fiscally responsible organizations Only three percent of the roughly 10,000 nonprofits evaluated have a 4-star rating: only a quarter of charities rated receive achieved this recognition nine consecutive times. The coveted this distinction. In 2011, Charity Navigator added 17 ranking indicates the Salk Institute outperforms most other metrics, focused on governance and ethical practices as charities in America in regard to executing best fiscal practices well as measures of openness, to its ratings methodology. and carrying out its mission in a financially responsible way. These accountability and transparency metrics, which account for 50 percent of a charity’s overall rating, reveal “We are grateful for the faithful generosity of our donors and this which charities operate in accordance with industry best recognition as we continue to pursue answers to challenging practices and whether they are open with their donors questions in cancer, neuroscience, genetics, immunology, aging, and stakeholders. Timothy Schoen

Schoen has served as president nine years prior to his time at There are many deserving causes worthy of support. That’s why and CEO of BioMed Realty since Healthpeak. He is also the chair of the Salk Institute takes great pride in carrying out its mission in 2016. Prior to his current role, he Salk’s Conquering Cancer Initiative a financially responsible manner. Thanks to Salk’s best fiscal held various executive management Advisory Committee. He received practices, those who support Salk can be confident their generosity positions at Healthpeak from a BS in finance and international will impact their designated field of research and, in turn, accelerate 2006 to 2011 and was executive business from Minnesota State the pace of scientific discovery at the Institute. vice president and CFO from 2011 University and earned his MBA from to 2016. Schoen served as vice the University of California, Irvine, LEARN MORE www.salk.edu/the-power-of-science president of corporate finance graduate school of management, at Kilroy Realty Corporation for where he was a Dean’s Scholar.

44 INSIDE SALK SUMMER 2020 WWW.SALK.EDU WWW.SALK.EDU INSIDE SALK SUMMER 2020 45 46 YOUTONG HUANG,PHD ALS diseaseprogression. called TAM receptorsfound onmicroglia, techniques toassesstheimpactofproteins sclerosis (ALS). Huangwillusevarious in thedevelopment ofamyotrophic lateral microglia arethoughttoplay acrucial role Brain andspinalimmunecellscalled pathology inamyotrophiclateralsclerosis Microglial TAM receptorsasmodulatorsof INSIDE SALK EVENTS SUMMER 2020 of women and girls in science. who will also actively foster the increased participation targeted toward supporting future scientific leaders early to attract traditional funding. The awards are pursue high-risk, high-reward research in stages too graduate students and postdoctoral researchers to Every year, the program provides crucial support to proud to share and celebrate their achievements. recipients was not possible this year, the Institute is While apublic event lauding the Women &Science SPECIAL AWARDS SALK WOMEN&SCIENCE RECIPIENTS OFTHE2020 | LEMKELAB

collaborators andmentors. They have fields asinnovators, groundbreakers, have pioneeredchanges withintheSTEAM Art andMathematics)fields.Recipients STEAM (Science, Technology, Engineering, achievements madeby women inthe Science. The award recognizes outstanding the Trailblazer Award fromSalk Women & Professor was honoredwith Joanne Chory TRAILBLAZER AWARD JOANNE CHORY RECEIVES ANDREEA MANOLE,PHD improved therapeuticstrategiesfor diseases. neurodegeneration, which couldleadto and neuroinflammationinthecontext of (PLA2G6 andGBA) tostudy metabolism in twogenesinvolved infat metabolism cells derived frompatientswithmutations Manole willuseinducedpluripotentstem glucocerebrosidase genetic defectsinphospholipaseA(2)and Neuroinflammation associatedwith | GAGELAB

BIANCA BARRIGA woman intheworld. such asFlorenceGriffith Joyner, thefastest athletefromrunners separates theordinary running—to better what understand movements—such aswalking and the mousespinalcordthathelpproduce Barriga willexamine theneuronswithin spinal neuralnetworks Investigating effectsofexercisetrainingon immunity andtheformation immunity ofscartissue. immune response,leadingtoanti-tumor induced celldeathtoseeifittriggersthe for cancer. McGeewillinvestigate radiation- the immuneresponsetoradiationtherapy There characterizing islimitedscientificdata microenvironments innate immunecellactivationinuniquetumor Investigating theroleofradiation-induced HEATHER MCGEE, MD, PHD awarded the2018 Breakthrough Prize have beenwidelyacclaimed.She was R.NewmanMaryam ChairinPlant Biology, investigator, andtheHoward H.and a Howard HughesMedicalInstitute in additiontoherrolesasaprofessor, Molecular andCellularBiologyLaboratory, Chory’s efforts leadingSalk’s Plant paths toachieve theirvision. personal realms. Trailblazers forge theirown advances inboththeirprofessional and dedicated theirlives tomakingsignificant | PFAFF LAB WWW.SALK.EDU | KAECH LAB

program housedat TED. through The Audacious Project, ahighlycompetitive chosen in2019 for fundingofmore than$35million change, was instrumental intheInstitute being root networkstohelpmitigatetheeffects of climate on creatingplantsthatstoremorecarbonintheir Salk’s HarnessingPlantsInitiative, which focuses National Academy ofInventors. Herwork leading in Life Sciencesandwas madeaFellow ofthe HSIUYI CHEN,PHD resistant human resistant T cells. confer toHIV, resistance todevelop HIV- differences betweenthetwospeciesthat infection. Chenwillexamine thegenetic todevelopingresistant AIDS after HIV extremely similar, yet chimps aremore The chimpanzee andhumangenomesare alleles with massively-parallel genome editing by introducingthousandsofchimpanzee Generating HIV-resistant humanCD4+ Tcells WWW.SALK.EDU RNA polymeraseIII. stem cellstoinvestigate themechanism of genetic modelsandpatient-derived neural therapies for thisdisease,Ningwill use neurodegenerative disease. To inform new leukodystrophy (HMLD),anearlyonset III causediseasessuch ashypomyelinating intheenzymeRNApolymerase Mutations neurodegenerative diseases to studyRNApolymeraseIII-related Establishing cellandmousemodels JIA NING,PHD | HUNTERLAB | MCVICKERLAB

development ofdisease. energy sourcesinaway thatpromotesthe resident immunecells,calledmicroglia,use infections may reprogramhow brain- how. Synder willexamine how viral researchers precisely donotunderstand with previous viralinfections, although Alzheimer’s diseaseisassociated Alzheimer’s disease reprogramming inlinkinginfectionto Determining theroleofmicroglialmetabolic ANNELISE SNYDER,PHD for pancreatictumors. detection andpossibletherapeutictargets The work couldreveal biomarkers for early cancer—affects gutbacteriapopulations. one ofthedeadliestcancers—pancreatic CA19-9, asugarmoleculeassociatedwith Chung willinvestigate how levels of microbiome Defining theroleofCA19-9inpancreatic SEJ CHUNG,PHD | ENGLELAB opportunities for the public and supporters to visit pandemic, supporters can still learn about Salk’s and has postponed events during the COVID-19 | its architectural masterwork and engage directly KAECHLAB While the Institute is currently closed to visitors cutting-edge discoveries and life-changing Salk has along tradition of offering unique

science at one of these virtual events: www.salk.edu/events/public-events www.salk.edu/events/public-events with world-renowned researchers. world-renowned with

JIN LAB SHARON (HSIANG-HSUAN)HUANG,MD cardiac pacemaker. such asgeneratingsufficient power torun a electrical signal,for biotherapeutic uses— (“mini organs”)thatcangeneratetheirown and eelstocreatespecialized organoids Xue willdraw inspirationfromelectric rays the mammaliansystem Creating biocompatibleelectricorganoidsfor that involve difficulty controllingactions. psychiatric diseases,such asschizophrenia, which willshedlightonneurologicaland integrates feedback tocontrolbehavior, Huang willinvestigate how thebrain in actionsequencing Dissecting theroleofsensorimotorfeedback YUAN XUE,PHD

INSIDE SALK | IZPISUABELMONTELAB SUMMER 2020

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48 INSIDE SALK EVENTS SUMMER 2020 Clodagh O’Shea Shadel; and Associate Professor Nicola Allen. Nicola Professor and Associate Shadel; Jan Karlseder, Lundblad Vicki and Hetzer; Professors Gerald Martin President Vice and Officer/ Chief Science Professor Salk scientists with andGage, discussion apanel Initiative the of by Salk Rusty President Foundation Research, an overview Medical for Glenn the of Mark Collins, from president presentation aguest eventThe featured diseases. to age-related contribute body the of systems major the fundamentals aging of and interactions between how amultidisciplinary the initiative new The approach uses and to understand others. including diseases, Alzheimer’s, cancer, most for risk factor diabetes biggest is the Aging 14, November On Optimizing Initiative. its Aging introduced Salk Institute the INTRODUCING SALK’S OPTIMAL AGING INITIATIVE Alan Saghatelian Gerald Shadel Gerald Salk Professor Joseph Noel. Joseph Salk Professor to help plants of ability climate mitigate change by the and on an investigation January 12, 2020, and Lucille Bax Chung piano on on Alessio of sounds beautiful to the treated were Attendees ShadelGerald and music pianist of Fei Fei Dong. Professor of science the with delighted guests 2019, November3, event on first The season. in events lineup the current the two from with on played &Music Series Salk Science The HITS THERIGHTNOTE SALK SCIENCE&MUSICSERIES through afull activities. of year scientists at Salk and with engage discovery scientific support who members community of generation Salkexcellerators are next the as groundbreaking medicines. precision devices biological to design and knowledge leveragethe disease of to unravelseeking complexities the Salkexcellerators group their about novel research and Alan the Saghatelian spoke with O’Shea Clodagh Salk Professors 26, February On SALKEXCELLERATORS WWW.SALK.EDU WWW.SALK.EDU throughout the year. scientists Institute’s the from to hear world-renowned public the opportunity the offers series lecture Basics to afullaging and auditorium. disease Back The to and play mitochondria in role mtDNA the discussed Audrey the holds Chair Geisel in Science, Biomedical 12, February cells. On of Shadel, who powerhouses the Shadel mitochondria, shared on his details about work Gerald Institute’s Initiative, Optimal Salk Professor Aging the of Highlighting as part avenue one research of MITOCHONDRIA SHADEL SHARES THE BASICS OF Gerald Shadel Nicola Allen, GeraldShadeland Vicki Lundblad From left: Jan Karlseder, Martin Hetzer, INSIDE SALK Salk President Rusty Gage SUMMER 2020 and Laura Benanti and Laura Michael Krajewski Michael Krajewski 49

EDUCATION OUTREACH HIGH SCHOOL SCIENCE DAY On February 29, Salk faculty and staff brought science to life for the next generation of scientists with the 30th March of Dimes High School Science Day. The half-day annual event is designed to encourage high school students to consider an exciting career in science and research. The Institute welcomed GroundbreakingGroundbreaking about 300 students from all over San Diego EVENTS who met Salk scientists and received behind- the-scenes, interactive lab tours. SalkSalk discoveries discoveries

Madison Dodds is the official podcast WhereWhere Cures Cures Begin Begin is the official podcast onon the the go! go! of the Salk Institute for Biological Studies. of the Salk Institute for Biological Studies. InIn each each episode, episode, co-hosts co-hosts Allie Allie Akmal Akmal and and BrittanyBrittany Fair Fair interview interview Salk Salk researchers researchers about about theirtheir bold bold research research efforts efforts and and learn learn about about thethe scientists’ scientists’ lives lives outside outside of of the the lab. lab. The Join first seasonus to hear shares how conversations Salk researchers with are President making andadvances Professor in neuroscience, Rusty Gage, Professor using plants Joanne to Choryfight climate and Assistant change, Professor developing Danielle cures for Engle,cancer, to mastering name a few. our Join circadian us to hearclock how and Salkmore. researchers are making advances in neuroscience, using plants to fight climate change,The podcast developing is available cures on for iTunes cancer,, Google masteringPlay and anywhere our circadian you clock listen and to podcasts. more.

TheTo learn podcast more, is availablevisit Salk.edu/podcast on iTunes, Google. Play and anywhere you listen to podcasts.

To learn more, visit Salk.edu/podcast.

SEASON 2 (AVAILABLE NOW): DONOR APPRECIATION EVENT Marga Behrens Uri Manor on the link On November 20, Salk supporters were SEASONon researching 2 (LAUNCHING betweenIN APRIL) mitochondria: and hearing loss honored for their generous contributions neuropsychiatric disorders leading to a productive year of science Wolfgang Busch on using Joseph Noel on using in 2019 at the Institute. Salk scientists plant roots to store carbon coastal ecosystems to fight climate change shared updates on current research Wolfgangdioxide Busch on Molly Matty on and how donor philanthropy accelerates using plant roots to store examining how bacteria Tatyana Sharpee on carbon dioxide can affect animal scientific discovery. The event was Martin Hetzer on how we perceive our attended by Salk leaders, Board understanding aging behavior Reuben Shaw on the link environment via our senses members, faculty, staff, volunteers and betweenMolly Matty metabolism on examining and Uri Manor on the link community donors. cancer betweenReuben Shawmitochondria on the link how bacteria can affect andbetween hearing metabolism loss and Josephanimal Noelbehavior on using cancer costal ecosystems to fight climate change

50 INSIDE SALK SUMMER 2020 WWW.SALK.EDU Rusty Gage President

Rebecca Newman Vice President, External Relations

Steven Johnson Groundbreaking Chief Communications Officer Kristina Grifantini Director, Scientific Communications Salk discoveries and Media Relations Allie Akmal THE POWER Where Cures BeginMedia is the Relations official Manager podcast on the go! of the Salk Institute for Biological Studies. Brittany Fair In each episode, co-hostsScience Writer Allie Akmal and Brittany Fair interview Salk researchers about Curtis Ippolito their bold researchDevelopment efforts and Writer learn about the scientists’ lives outside of the lab. The first OF SCIENCE season shares conversationsAaron Howard with President Video Communications Manager LECTURE SERIES and Professor Rusty Gage, Professor Joanne Chory and AssistantLiz Professor Hincks Danielle Director of Digital and Engle, to name a few.Graphic Join Communications us to hear how We are reminded during these sobering times of how critical basic Salk researchers are making advances in John McDonagh scientific research is to our health, our community and the globe. It was neuroscience, usingSenior plants Web toDeveloper fight climate change, developing cures for cancer, the basic scientific research of the Institute’s founder, Jonas Salk, that Stephanie Harada led to the first safe and effective polio vaccine, saving countless lives. mastering our circadianWeb Designer clock and more.

At Salk, world-renowned experts in immunology, infectious diseases, Chris Keeney The podcast is available on iTunes, Google virology and other topics are similarly uncovering the fundamentals of Photographer Play and anywhere you listen to podcasts. biology and disease. From deadly viruses and cancer, to Alzheimer’s and Oliver Yambao Senior Graphic Designer climate change, Salk scientists are on the front lines of discovery. Learn To learn more, visit Salk.edu/podcast. about how these researchers are tackling the biggest challenges facing Sara Jacobsen Graphic Designer the world in this timely series. Amy Cao Science Illustrator Please check the link for upcoming virtual SEASON 2 (LAUNCHING IN APRIL): lectures where you can hear directly from scientists on their life-changing work. www.salk.edu/powerofscience Visit the Salk Institute at www.salk.edu. Wolfgang Busch on Molly Matty on using plant roots to storeInside Salkexamining is published how by bacteriathe Salk Institute carbon dioxide for Biologicalcan affectStudies. animal Please send comments to [email protected] or contact Reuben Shaw on the linkthe Communications Department at between metabolism and(858) 453-4100Uri Manor x1371. on the link cancer between mitochondria Inside Salkand is hearingprinted on loss recycled paper. Joseph Noel on using costal ecosystems to fight climate change NONPROFIT ORG. U.S. POSTAGE PAID PERMIT NO. 611 SAN DIEGO, CA

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