Project Grant R35GM161690
- The National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health, awarded The Trustees of the University of Pennsylvania $555,428 on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to define the mechanistic underpinnings of AAA+ disaggregases, specifically HSP104 and its partial human homolog SKD3 (human CLPB). The research program seeks to understand at a fundamental level how HSP104 couples ATP...
- The National Institute of General Medical Sciences awarded The Regents of the University of California, San Francisco $551,000 on September 3, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop function-selective modulators of multifunctional hub proteins. The research expands two programs: developing molecular glues to stabilize native protein-protein interactions and establishing technologies to study dynamic protein-interaction networks. The work...
- The National Institute of General Medical Sciences awarded The Regents of the University of California, San Francisco $2.255 million under the Biomedical Research and Research Training program (CFDA 93.859) on September 1, 2026. The award funds development, application, and dissemination of integrative structure modeling methods for computing structural and spatiotemporal models of biomolecular complexes. The recipient will expand the scope of the open-source Integrative Modeling Platform...
- The National Institute of General Medical Sciences awarded The Regents of the University of California, San Francisco $562,484 on May 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop next-generation visualization and analysis software for multiscale molecular modeling. The recipient will create cutting-edge software tools that integrate visualizations and analyses of molecular structures and related biological information, including...
- The National Institute of General Medical Sciences awarded the University of California, San Diego $440,000 on July 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to conduct research on membrane-protein interactions that control mitochondrial shape and function. The research develops multiscale biophysical tools and computer simulations to integrate molecular details into models of large-scale membrane bending in mitochondria. The work addresses two problem...
- The National Institute of General Medical Sciences (NIGMS) of the Department of Health and Human Services awarded the University of California, Berkeley $287,221 in project grant funding on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859). The award funds research into the molecular dynamics of biomolecules and their interactions, with emphasis on fusing biophysics and machine learning approaches. The work develops rigorous computational models and...
- The National Institute of General Medical Sciences awarded the University of California, Santa Barbara $391,250 on May 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop computational methodologies for studying liquid-liquid phase separation of intrinsically disordered proteins. The research integrates artificial intelligence protein-language models with multiscale computational simulations to characterize biomolecular condensates formed by phase...
- The National Institute of General Medical Sciences awarded $124,767 to The Regents of the University of California, San Francisco on May 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to advance de novo protein design for catalysis and fluorescence imaging. The research tests the hypothesis that protein dynamics, particularly enrichment of productive conformations, contribute to enhanced catalytic rates in engineered proteins. Prior work under this funding...
- The National Institute of General Medical Sciences awarded the University of California Santa Cruz $425,033 on July 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to map variant histone protein interactions and elucidate the molecular mechanisms governing those interactions through advanced proteomics and structural biology. Over the five-year performance period (July 1, 2026 through April 30, 2031), the principal investigator will use nucleosome...
- The National Institute of General Medical Sciences awarded the University of California, San Diego $384,394 on August 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to investigate molecular determinants of lipid-protein recognition through computational and experimental approaches. The research integrates deep-learning, molecular dynamics simulation, and de novo protein design to characterize biophysical interactions governing binding affinity and...
The National Institute of General Medical Sciences awarded The Regents of the University of California, San Francisco $2.1 million on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to support structural and mechanistic research on AAA+ chaperone proteins and their role in protein disaggregation and homeostasis. The award funds cryo-electron microscopy studies of conserved AAA+ family members, including yeast HSP104, bacterial CLP proteins, human P97 (VCP), and human mitochondrial SKD3 (CLPB), to determine atomic-resolution structures of biochemically defined active complexes during substrate unfolding, translocation, and proteolysis. Research addresses how AAA+ atpases function as ATP-driven unfoldases and disaggregases that translocate polypeptide substrates through central channels, with unfolded proteins subsequently refolded by molecular chaperones or degraded by proteases. Prior funding has yielded substrate-bound structures of HSP104 in distinct translocation states, revealing a rotary hand-over-hand mechanism with substrate gripping, release, and two-amino-acid translocation steps, as well as structures of the CLPAP protease during active substrate processing and the HSP104:HSP70 substrate loading complex. Improved understanding of proteostasis pathway mechanisms targets therapeutic intervention points for neurodegenerative diseases including Alzheimer's disease and protein misfolding-related disorders that arise during cell stress and aging. Work is performed in San Francisco, California. The period of performance runs September 1, 2026, through August 31, 2030.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $2.1m | 8/17/26 |