Project Grant R35GM164097
- 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...
- The National Institute of General Medical Sciences awarded The Trustees of The University of Pennsylvania $881,151 on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to investigate the structural, biochemical, and biophysical properties of cytoskeletal motor proteins, specifically myosin paralogs and their interactions with regulatory partners and actin dynamics. Research activities include structural studies to explore force generation, regulation,...
- The National Institute of General Medical Sciences awarded the University of Pennsylvania $924,095 on April 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to investigate molecular mechanisms controlling actin cytoskeleton dynamics. The research addresses four major knowledge gaps: the ARP2/3 complex's role in actin filament branching and regulation by nucleotide state and binding proteins; filament dynamics at barbed and pointed ends, including cooperative...
- The National Institute of General Medical Sciences awarded The Trustees of The University of Pennsylvania $125,000 on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to support research on membrane remodeling by membrane-bound motors. The project investigates how class I myosin (myosin-I) couples actin filaments to lipid membranes at the actin-membrane interface, bridging a gap in understanding how cells coordinate mechanical forces and membrane...
- The National Institute of General Medical Sciences, part of the National Institutes of Health, awarded $345,581 to the University of Pennsylvania on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to visualize and characterize how bacteria and archaea use DNA-bending proteins to fold genomic DNA into three-dimensional shapes that regulate CRISPR-associated integrase function during adaptive immunity to phage infection. The project will employ...
- The National Institute of General Medical Sciences awarded $418,263 to The Trustees Of The University Of Pennsylvania on August 15, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop methods for rational design of therapeutic siRNA conjugates, with focus on antibody-siRNA conjugate (ARC) delivery to non-hepatic cells. The funded work addresses barriers to extra-hepatic siRNA-conjugate therapy by developing a new method to quantify receptor dynamics on cell...
- 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 Arthritis and Musculoskeletal and Skin Diseases awarded The Trustees of The University of Pennsylvania $473,221 on September 4, 2026, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846). The research investigates thin-filament length regulation in muscle sarcomeres, focusing on the structural and functional mechanisms that control filament length and its dysregulation in skeletal and cardiac muscle diseases including nemaline myopathy...
- The National Institute of General Medical Sciences awarded the University of Pennsylvania $406,250 on March 2, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to advance nucleic acid chemistry and synthetic biology for RNA therapeutics. The research program develops de novo xeno nucleic acids (XNAs)—synthetic nucleic acid analogs with modified backbones that enhance nuclease resistance and extend half-life—to expand the genetic toolkit for RNA silencing and...
- The National Institute of General Medical Sciences awarded $406,250 to the University of Pennsylvania on March 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop statistical and computational methods for analyzing complex multimodal biological datasets. The recipient will develop correlated latent factor models to extend multi-omic inference capabilities across complex study designs, including model-based imputation methods for handling missing data...
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 hydrolysis to the disaggregation of diverse protein structures including disordered aggregates, preamyloid oligomers, phase-separated condensates, prions, and amyloids. The investigators have engineered potentiated HSP104 variants that dissolve fibrils formed by alpha-synuclein, TDP-43, and FUS, and have developed variants with refined collaboration with HSP70 or selectivity for alpha-synuclein to minimize off-target toxicity. The work also focuses on SKD3, a mitochondrial AAA+ protein with powerful protein disaggregase activity; mutations in SKD3 underlie severe mitochondrial disorders. Current investigations address how HSP104 translocates substrates during disaggregation, how to engineer HSP104 variants with selectivity for specific targets, and related mechanistic questions that currently limit understanding of how these disaggregases operate. The award carries a period of performance from September 1, 2026, through August 31, 2031, with place of performance in Philadelphia, Pennsylvania.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $555.4k | 8/17/26 |