Westlake Master Mini-symposium

来源:科技合作部 发布时间:2019-08-07 作者:科技合作部


Time: 09:00-11:30, Saturday, August 17, 2019


Venue: Lecture Hall, 1st Floor, Building 5, Yunqi Campus

主持人:新葡萄京娱乐场生命科学学院讲席教授 许田

Host: Tian Xu, Chair Professor, School of Life Sciences, Westlake University




会议议程 Agenda



Prof. Dinshaw J. Patel

Structural Biology of CRISPR-Cas Surveillance Complexes


Prof. Robert Roeder

Mechanisms of Transcriptional Regulation through Diverse Coactivators




Dr. Bobo Dang

Applying Chemistry to Biological Systems through Synthetic and Engineering Approaches


Dr. Qi Hu

Disease-Causing Mutations in the G Protein Gαs Subvert the Roles of GDP and GTP



1. 主讲嘉宾/SpeakerDinshaw J. Patel, Ph.D.

Professor, Structural Biology Program, Memorial Sloan-Kettering Cancer Center; Member, National Academy of Sciences, USA; Member, American Academy of Arts and Sciences

题目/Title: Structural Biology of CRISPR-Cas Surveillance Complexes

Dr. Patel received his bachelor's degree in chemistry from the University of Mumbai in 1961 and completed a master's degree at the California Institute of Technology in 1963. He then joined the laboratory of David Schuster at New York University, from which he received his Ph.D. in chemistry in 1968. After completing his Ph.D., Patel worked as a postdoctoral fellow with Robert Chambers at NYU. In 1984 Patel became a professor of biochemistry and molecular biophysics at Columbia University Medical Center, where his research group focused on using NMR to study double-stranded DNAstructures. He was recruited by Paul Marks at Memorial Sloan Kettering Cancer Center to move his laboratory and work to develop the institution's new program in structural biology, alongside colleague James Rothman. Following the move in 1992, Patel expanded his research interests into X-ray crystallography and RNA structure. Patel was elected to the National Academy of Sciences in 2009 and to the American Academy of Arts and Sciences in 2014.

His laboratory studies the structural biology of macromolecular recognition, including RNA catalysis, RNA interference, and bypass of DNA damage.


The role of RNA in information transfer and catalysis highlights its dual functionalities. Our ongoing research on RNA-mediated gene regulation has focused on CRISPR-Cas pathways involving ternary complexes of recently identified single-subunit Cas12 surveillance complexes with bound guide RNA and target DNA.

The lecture component on multi-subunit CRISPR-Cas complexes will focus on the type I-A Csy and III-A Csm systems. In the type III-A Csm system, we shall address mechanisms of target RNA binding and cleavage, as well as target RNA-activated ssDNA cleavage in the HEPN pocket and cyclic oligoadenylate (cOA) formation from ATP in the Palm pocket. We will also highlight a timer mechanism whereby successive nicks of bound cOA within the CARF domain regulate the trans-acting Csm6 RNase activity of the adjacent HEPN domain.

We have also investigated the impact of anti-CRISPR proteins in suppressing single- and multi-subunit CRISPR-Cas host defense pathways.

The above studies were undertaken by postdocs Hui Yang (x-ray studies on single-subunit Cas 12), Hui Yang and the Sriram Subramaniam group at NCI (cryo-EM studies on multi-subunit type 1 Csy) and Ning Jia (x-ray and cryo-EM studies on multi-subunit type III-A Csm).


2. 主讲嘉宾/SpeakerRobert G. Roeder, Ph.D.

Arnold and Mabel Beckman Professor of Biochemistry and Molecular Biology, The Rockefeller University; Member, National Academy of Sciences, USA; Member, American Academy of Arts and Sciences

 题目/Title: Mechanisms of transcriptional regulation through diverse coactivators

Dr. Roeder received his B.A. in chemistry from Wabash College and his M.S. in chemistry from the University of Illinois. He received his Ph.D. in biochemistry in 1969 from the University of Washington, Seattle, where he worked with William J. Rutter and did his postdoctoral work at the Carnegie Institution of Washington, in Baltimore, from 1969 to 1971.

He was professor at Washington University School of Medicine in St. Louis from 1976 to 1982. Later he joined The Rockefeller University and was named Arnold and Mabel Beckman Professor. He was elected as a member of the National Academy of Sciences in 1988 and the American Academy of Arts and Sciences in 1995, and a foreign associate member of the European Molecular Biology Organization in 2003.

His lab’s current activities focus on transcriptional activators important for homeostasis (nuclear hormone receptors); lymphoid cell differentiation (E2A, OCT1/2, OCA-B), lymphoid malignancy (E2A-PBX1, AML1-ETO, and MLL1-AF9 leukemogenic fusion proteins); and tumor suppression (p53).


Transcriptional regulation by gene- and cell-specific DNA-binding factors underlies key events in development, cell differentiation and cell transformation. However, their effects on specific genes depend upon complex arrays of cofactors (coactivators and co-repressors) that include both chromatin remodeling/histone modifying factors (e.g., the p300/CBP histone acetyl-transferases and the SET1/MLL H3K4 methyl-transferases) and other general (e.g., Mediator, TAFs) and cell-specific (e.g., OCA-B, PGC-1) cofactors that facilitate more direct communication between enhancer-bound regulatory factors and the general transcription machinery at core promoters/transcription start sites. Emphasizing biochemical studies with cell-free systems reconstituted with recombinant chromatin templates and purified transcription factors, as well as cell-based and genetic analyses, the cooperative functions and mechanism of action of various co-activators will be discussed in relation to gene regulation by selected activators (p53, nuclear receptors, B cell factors, or leukemic fusion proteins).


3. 主讲嘉宾/SpeakerBobo Dang, Ph.D.

PI of School of Life Sciences, Westlake University

题目/Title: Applying Chemistry to Biological Systems through Synthetic and Engineering Approaches

Bobo Dang received his B.S. from School of Chemistry and Chemical Engineering at Nanjing University and Ph.D. from Department of Chemistry at the University of Chicago. He then did his post-doctoral work at the Department of Pharmaceutical Chemistry, UCSF. Bobo Dang is now a faculty member at School of Life Sciences, Westlake University. Fascinated by protein molecules, he has focused research on studying the structure, function and biological activities of protein molecules through chemical synthesis, computational design and biological display technologies. He also has strong interests in developing protein based technologies to probe biological systems and to advance protein therapeutics.


Chemical protein synthesis provides atomic control of protein structures and enables protein modifications in unprecedented ways, high throughput selection offers the possibility to engineer proteins in unpredictable ways. Using chemical protein synthesis, we established novel methodologies to synthesize and engineer venom protein toxins. Built on the synthesis, we invented a method to optically activate neurons without using genetics, which may enable potential treatments for macular degeneration. Utilizing high throughput protein selection, we invented a method (SNAC-tag) to achieve site-specific chemical protein cleavage, which can replace enzymes during recombinant protein expression and purification and thus can get rid of all the problems associated with proteolytic cleavage. Based on the mechanistic studies of this chemical protein cleavage method, we are now trying to develop novel ways to synthesize and engineer proteins.


4. 主讲嘉宾/SpeakerQi Hu, Ph.D.

PI of School of Life Sciences, Westlake University

题目/Title: Disease-Causing Mutations in the G Protein Gαs Subvert the Roles of GDP and GTP

Dr. Hu received his PhD in biology at Tsinghua University in 2014. Then he did his postdoctoral training in Prof. Kevan Shokat’s lab in the University of California, San Francisco from 2015 to 2019. He received Damon Runyon Fellowship Award in 2015. He joined the Westlake University in 2019 as an Assistant Professor. The study in the Hu lab is focusing on protein palmitoylation. Using biological and chemical tools, the Hu lab is aiming to understand the molecular mechanism underlying the function of DHHC family palmitoyltransferases and to develop small molecule inhibitors of these palmitoyltransferases.


The single most frequent cancer-causing mutation across all heterotrimeric G proteins is R201C in Gαs. The current model explaining the gain-of-function activity of the R201 mutations is through the loss of GTPase activity and resulting inability to switch off to the GDP state. We find that the R201C mutation can bypass the need for GTP binding by directly activating GDP-bound Gαs through stabilization of an intramolecular hydrogen bond network. Having found that a gain-of-function mutation can convert GDP into an activator, we postulated that a reciprocal mutation might disrupt the normal role of GTP. Indeed, we found R228C, a loss-of-function mutation in Gαs that causes pseudohypoparathyroidism type 1a (PHP-Ia), compromised the adenylyl cyclase-activating activity of Gαs bound to a non-hydrolyzable GTP analog. These findings show that disease-causing mutations in Gαs can subvert the canonical roles of GDP and GTP, providing new insights into the regulation mechanism of G proteins.



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July 31, 2019