When traditional funding sources and federal programs were slow to mobilize at the onset of the coronavirus pandemic, UCSF researchers and clinicians faced the hard realization that no one was going to ride in and save the day.
Though many began focusing on how to address the crisis, they lacked the resources needed to pursue their ideas. That was until Allen & Company stepped forward with a lead gift to support UCSF’s Sandler Program for Breakthrough Biomedical Research (PBBR). UCSF Chancellor Sam Hawgood saw the potential in the gift’s impact and matched the amount through the COVID-19 Response Fund, effectively empowering PBBR (pronounced “pibber”) to jump-start innovative coronavirus-related projects. Now UCSF’s experts are rallying to demystify the SARS-CoV-2 virus and COVID-19, the disease it causes.
“PBBR is going to be the cavalry for basic and applied research in the San Francisco Bay Area with respect to COVID-19,” said Joe DeRisi, PhD, director of PBBR and co-president of the Chan Zuckerberg Biohub. “The traditional PBBR grant cycle funds seed grants in a wide variety of basic science areas from neurobiology to cell biology to genetics. What we needed here was something immediate that would channel the energy of our researchers in one particular area: COVID virology.”
“I have been a fan of UCSF since my friend Reid Hoffman brought me to a research workshop with Joe DeRisi a few years ago,” said Herb Allen III, president of Allen & Company. “It was an easy decision to bet on the brilliance and dedication of Joe and his colleagues at UCSF as they pour themselves into decoding COVID-19 and the pioneering science that will benefit all of us.”
Rather than requiring lengthy proposals, hard-to-come-by preliminary data, and months of deliberation before funds are awarded, PBBR expedites the typical funding cycle for scientific studies. The new infusion of funds allowed PBBR to start an off-cycle funding round in April, creating a call for UCSF researchers to take the lead and find ways to address the pandemic.
“The program invited researchers to propose relevant projects that align with PBBR principles – innovative, bold, and risky thinking and approaches that might fail, but if successful, would be highly impactful,” said Keith Yamamoto, PhD, UCSF vice chancellor for science policy and strategy and PBBR’s inaugural faculty director who has overseen the program for its first two decades.
PBBR leaders promised that funding could be secured quickly and simply. Given only a week of lead time, UCSF researchers across the institution generated a remarkable spectrum of innovative proposals to better understand SARS-Cov-2, to detect and diagnose infection, and to address the COVID-19 public health crisis.
When the one-week proposal submission period ended, PBBR immediately made $2 million of funds available to researchers. Twenty-three project teams received awards of between $50,000 and $200,000.
During this funding round, the PBBR review committee found it striking that disparate elements of UCSF’s basic, clinical, and population research communities converged so efficiently and effectively. The awarded projects represent a wide range of strategies and approaches, pioneered in many cases by teams that combine significantly different areas of knowledge. They cover UCSF’s research expertise in the computational, molecular, structural, cellular, tissue, or organismal fields; they focus on describing or analyzing pathways, mechanisms, or outcomes of viral infection; and they dive into studying the spread, pathogenicity, cell biology, diagnostics, therapeutics, and population health – all related to SARS CoV-2 and attack COVID-19.
“Our goal was to unleash the imagination, brilliance, and energy of the UCSF research community to create new and effective ways to understand SARS-CoV-2 and attack COVID-19,” Yamamoto said. “We hope that the knowledge gained and technologies developed from these 23 projects will help address the initial wave of this pandemic and better prepare for subsequent waves, as well as for other infectious diseases going forward.”
In 1997, Herb and Marion Sandler established PBBR to empower UCSF scientists to pursue basic science projects and cutting-edge ideas with the potential for enormous transformative impact. The Sandlers relished providing support to young scientists who bucked conventional wisdom and challenged the status quo. Each year, PBBR supports dozens of investigators whose bold ideas and revolutionary research have the potential to uncover unprecedented advances in science and medicine. Fueled primarily by philanthropy, PBBR represents just 0.5 percent of UCSF’s overall research budget but has unrivaled leverage. PBBR award winners have made discoveries that have produced more than $1.4 billion in subsequent follow-on funding and an additional $347 million in indirect cost recovery for the UCSF campus. PBBR projects also have generated more than 3,000 peer-reviewed scientific publications, almost 90 patents, and more than 300 National Institutes of Health research grants.
Tanja Kortemme, PhD; and Aashish Manglik, MD, PhD
Super-ACEs: engineering ACE2-based and de novo proteins to prevent and treat SARS-CoV-2 infections
Marina Sirota, PhD; and Chaz Langelier, MD, PhD
Transcriptomics-based computational drug repositioning for COVID-19 treatment
Xiaokun Shu, PhD
Designing imaging reporters of the spike protein and ACE2 interaction for screening inhibitors that block SARS-CoV-2 entry into human cells
Hana El-Samad, PhD
Viral pathogen detection by genetically encoded responses
Aashish Manglik, MD, PhD; and Peter Walter, PhD
Aerosol-based passive immunization for SARS-CoV-2 using synthetic nanobodies
Yifan Cheng, PhD; Charles Craik, PhD; and Aashish Manglik, MD, PhD
Structural basis of humoral immunity to the SARS-CoV-2 spike protein
Cliff Lowell, MD, PhD; and Satish Pillai, PhD
Development of a novel mouse model of COVID-19 disease
Zev Gartner, PhD
A high-throughput screening platform for identifying broadly neutralizing antibodies against SARS-CoV-2
Nadia Roan, PhD; Sulggi Lee, MD, PhD; Joshua Vasquez, MD; and Eliver Ghosn, PhD
Characterization of B-cell and antibody responses associated with efficient recovery from COVID-19
Jeremy Reiter, MD, PhD
Understanding and drugging SARS-CoV-2 nsp13
Shaeri Mukherjee, PhD
Repurposing of the secretory and membrane trafficking pathway by SARS-CoV-2
Koh Fujinaga, PhD; and Matija Peterlin, MD
Identification of antiviral agents targeting SARS-CoV-2 replication
Jim Wells, PhD
Development of recombinant antibodies for SARS-CoV-2 diagnostics and therapeutics
John Gross, PhD; Brian Shoichet, PhD; and Jack Taunton, PhD
Discovery of small-molecule inhibitors of SARS-CoV-2 by targeting the essential enzyme nsp16
Jack Taunton, PhD; Davide Ruggero, PhD; and Melanie Ott, MD, PhD
Targeting viral protein biogenesis as a therapeutic strategy for COVID-19
Keith Mostov, MD, PhD
Secretory IgA for passive mucosal immunization against SARS-CoV-2
Melanie Ott, MD, PhD; and Michael McManus, PhD
Orthogonal CRISPR screens to identify COVID-19 polytherapies
Michael Keiser, PhD
Learning the key molecular interactions of drug candidates targeting SARS-CoV-2 proteins
David Morgan, PhD
Phosphoregulation of the SARS-CoV-2 nucleocapsid (N) protein
Bill DeGrado, PhD; and Michael Grabe, PhD
De novo design of small proteins that bind the spike protein of SARS-CoV-2
Bruce Wang, MD; Franklin Huang, MD, PhD; Michael Kattah, MD, PhD; and Tien Peng, MD
Transcriptomic features of cellular and tissue pathogenesis of SARS-CoV-2 infection in human tissues
Diane Havlir, MD (pictured above); Bryan Greenhouse, MD; and Gabriel Chamie, MD
SARS-CoV-2 transmission dynamics in longitudinal population-level assessments in the Mission District
Jeremy Reiter, MD, PhD; Melanie Ott, MD, PhD; David Erle, MD; and Semil Choksi, PhD
Mapping SARS-CoV-2 infection, replication, and transcriptional responses in human airway epithelial cells