The Center for Research on Integrative Structural Proteomics (CRISP)

Science and technology have advanced to a point where large-scale protein-centered datasets generated through mass spectrometry (MS), cryo-electron microscopy (CryoEM), and cryo-electron tomography (Cryo-ET), together with developments in artificial intelligence, can provide unprecedented insight into molecular and cellular biology and inform new approaches to understanding human disease. In response to these advances, QBI established the Center for Research on Integrative Structural Proteomics (CRISP) to integrate multi-modal structural and proteomic datasets and apply them to the molecular characterization of healthy and diseased cells. 

CRISP combines complementary MS-based approaches— including global proteomics, native MS, co-fractionation MS, hydrogen/deuterium exchange MS, and cross-linking MS— with structural analyses by Cryo-EM and Cryo-ET, ultimately integrated through sophisticated modeling approaches and AI-guided structural predictions. These integrated approaches support the study of protein complexes, intracellular protein networks, and cellular architecture across multiple spatial scales. By linking structural, proteomic, and genomic information, CRISP enables deeper investigation of how molecular disruptions through genetic mutation, infectious disease proteins, or toxic agents can contribute to disease biology and therapeutic response.

CRISP develops integrated technological and analytical pipelines that interrogate the proteomic consequences of genetic variation linked to human disease. The center's efforts will support mechanistic studies of biological dysfunction and facilitate structurally informed approaches to therapeutic development and precision medicine. 

CRISP will draw on UCSF’s collaborative research ecosystem, including expertise in Cryo-EM, CryoET, and MS proteomics within QBI; AI and computational modeling through the UCSF/Enso partnership; and emerging Cryo-ET technologies developed in collaboration with CZ Biohub initiatives. In addition to advancing interdisciplinary research, CRISP aims to support scientific exchange and training through structural proteomics symposia, workshops, and collaborative programs that connect academic and industry investigators across instrumentation, computation, and biology.