The Dinshaw Patel Lab

Our group applies structural (cryo-EM, x-ray crystallography and NMR), biochemical and biophysical methods together with functional studies to investigate macromolecular-mediated recognition, regulation and catalysis. The ongoing major projects in the laboratory focus on the structural biology of CRISPR-Cas surveillance complexes and their suppression by anti-CRISPR proteins (in collaboration with Luciano Marraffini, Rockefeller), on Structure Maintenance of Chromosome Smc5/6 (with Xiaolan Zhao, MSKCC) and MRX (with John Petrini, MSKCC) complexes involved in double-strand break and stalled replication fork repair, and on complexes mediating the meiotic recombination pathway (with Scott Keeney, MSKCC). In addition, research is focused on protein-RNA complexes mediating the piRNA pathway (with Julius Brennecke, IMBA-Austria), on identification and characterization of small molecule inhibitors targeted to proteins of the cGAS-STING pathway and the SARS-CoV-2 family (with Thomas Tuschl, Rockefeller) and those that impact on proteins triggering the onset of acute myeloid leukemia (with Michael Kharas, MSKCC).

Our group retains an interest in the areas of structure-function studies of RNA interference mediated by siRNA pathway, and on post-translation histone and DNA modifications impacting on epigenetic regulation. Additional areas include RNA-mediated events ranging from cofactor recognition by riboswitches, catalysis by ribozymes and protein-RNA recognition events impacting on disease syndromes and the principles underlying the molecular basis of glycosphingolipid and phospholipid binding specificity by lipid transfer proteins.

Meeske, A. J., Jia, N., Cassel, A., Kozlova, A., Liao, J., Wiedman, M., Patel, D. J. & Marraffini, L. A. (2020). Phage-encoded anti-CRISPR enables full escape from type VIA CRISPR-Cas immunity. Science 369, 54-59.

Li, W., et al., Gozani, O., Patel, D. J. & Wang, Z. (2021). Molecular basis of nucleosomal H3K36 methylation by NSD methyltransferases. Nature 590, 498-503.

Rostol, J.T., Xie, W., Kuryavyi, V., Kao, K., Fromm, R., Patel, D. J. & Marraffini, L. A. (2021). The Card1 nuclease provides bacterial defense during Type III CRISPR immunity. Nature 590, 624-629.

Wang, J., Catania, S., Wang, C., de la Cruz, M. J., Rao, B., Madhani, H. & Patel, D. J. (2022). SNF2 ATPase remodels DNA methyltransferase to enable durable epigenetic memory. Mol. Cell 82, 1186-1198.

Yu, Y., Li, S., Ser, Z., Kuang, H., Than, T., Guan, D., Zhao, X. & Patel, D. J. Cryo-EM structure of DNA-bound Smc5/6 reveals DNA clamping enabled multi-subunit conformational changes. Proc. Natl. Acad. Scis. USA in press.

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Research Projects

• CRISPR-Cas and cGAS-STING Surveillance Pathways
• DNA Double Strand Break Repair Pathways
• Readout of Histone and DNA Epigenetic Marks
• siRNA and piRNA Biogenesis and Silencing
• Molecular Chaperone and Transfer Proteins