医学创新论坛第93期

时间：2026年3月25日（周三）下午16:00

地点：首都医科大学基础科研楼北楼二层科创汇堂

主持人：

李国民

首都医学科学创新中心

报告人：

Dinshaw J. Patel

教授

Memorial Sloan-Kettering Cancer Center

报告题目：

Antiphage defense by CARF-effector and protective deity systems

摘要：

The arms race between bacteria and viruses has given rise to the dynamic pan-genome composed of a combination of bacterial sensor-effector surveillance complexes. Following viral infection, a viral trigger activates the sensor protein, that in turn activates effector proteins, thereby promoting antiviral defense through either targeted nuclease activity, depletion of cellular metabolites or disruption of host cell membrane functions. Notably, antiviral defense capitalizes on an abortive infection mechanism, whereby infected cells die prior to completion of the phage replication cycle, insuring survival of the colony. Given that these systems have developed multiple, sophisticated avenues of active defense, in the process collectively constituting an "immune system", it is critical to deduce a mechanistic understanding of these diverse defense pathways, thereby opening new opportunities for biotechnological and biomedical applications.

The first half of the lecture will focus on type III CRISPR-generated cyclic oligoadenylates (cOAs) that target CARF domains to activate linked effector domains. The focus will be on effectors in these CARF-effector cassettes that are nucleases, transmembrane domains, deaminases and NADases, with the emphasis on the role of oligomerization and filament formation in antiphage defense.

The second half of the lecture will capitalize on the richness of newly identified prokaryotic antiviral defense systems, opening opportunities for characterizing the diversity of mechanisms of bacterial antiviral immunity and its evolutionary adaptation by metazoans.

The focus will be on Pucsar and Lamassu defense systems where we will highlight a new principle, whereby release of the sequestered effector on phage-mediated activation, triggers a conformational change-mediated oligomerization/filamentation required for effector catalytic function. By contrast, studies on the PUA-Cal-HAD antiphage defense system identifies m6-dAMP as a methylome-derived trigger produced specifically during phage-driven host chromosome degradation, that converts a preassembled hexameric assembly into an immune filament, that rapidly collapses cellular dNTP pools, thereby aborts infection.

报告人简介：

Dr. Patel's research has focused on the structural biology (NMR, x-ray and cryo-EM) of riboswitches and ribozymes, RNA interference, readout of histone and DNA epigenetic marks, the cGAS-STING pathway, CRISPR-Cas surveillance complexes, Structural of Maintenance Chromosomal (SMC) complexes and bacterial antiphage defense pathways.

Dr. Patel was elected to the National Academy of Sciences in 2009 and to the American Academy of Arts and Sciences in 2014. He has been awarded the Tan Jiazhen International Life Sciences Collaboration Award in 2019 and the Shizhang Bei International Award in 2023. He was made an Honorary Professor of Tsinghua University in 2024. 

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