北京大学定量生物学中心

学术报告 

题    目:  Cooperative signaling in chemoreceptor cluster: a reappraisal

报告人:  Professor Yuhai Tu

IBM Thomas J. Watson Research Center, Yorktown Heights, NY USA

AAAS Fellow, APS Fellow, Chair of the APS Division of Biophysics (DBIO)

时  间: 11月5日（周二）10:00-11:00

地    点: 吕志和楼B101

主持人: 汤超 教授

摘要:

Bacterial chemotaxis has been studied extensively in the past decades. On the theory side, the chemoreceptor cluster has been successfully modeled by using the classical Monod-Wyman-Changeux (MWC) model a key part of the “standard model” for bacterial chemotaxis that explains many aspects of the bacterial chemosensory system such as accurate adaptation and signal amplification quantitatively1.  However, although the MWC model explains the large shifts (orders of magnitude) in the kinase response curve caused by a large change in the receptor methylation level, it is inconsistent with the observation that the ligand occupancy curve only shifts slightly (a few fold) for the same receptor methylation level change.

In this talk, we describe our recent work to develop a nonequilibrium model that explicitly includes the phosphorylation-dephosphorylation cycle powered by ATP hydrolysis, which drive the system out of equilibrium. Our model successfully resolves the binding-kinase activity discrepancy. More importantly, it reveals the possible underlying mechanism that while ligand binding affects the ON/OFF switching of the kinase activity, receptor methylation affects the phosphorylation rate of the On-state. Our study also shows that a minimum energy dissipation is needed to maintain the observed sensitivity range and amplitude of the kinase response2.

Time permits, we will describe our most recent work3 in developing a nonequilibrium lattice model that explicitly combine the nonequilibrium phosphorylation-dephosphorylation dynamics for individual receptor functional units and cooperative unit-unit interactions within the extended receptor array. We show that the nonequilibrium lattice model explains the asymmetric switching dynamics observed in single-cell FRET experiments. Our study reveals that strong dissipation can enable sensitive and rapid response by easing the speed-sensitivity trade-off, which may serve as a general principle for cooperative signaling in biological systems.

Reference

1. “Quantitative Modeling of Bacterial Chemotaxis: Signal Amplification and Accurate Adaptation”, Yuhai Tu, Annu. Rev. Biophys. 2013. 42: 337-59.
2. “A nonequilibrium allosteric model for receptor-kinase complexes: The role of energy dissipation in chemotaxis signaling”, David Hathcock, Qiwei Yu, Bernardo A. Mello, Divya N. Amind, Gerald L. Hazelbauer, and Yuhai Tu, PNAS, 120 (42), 2023.
3.  “Time-reversal symmetry breaking in the chemosensory array reveals a general mechanism for dissipation-enhanced cooperative sensing”, David Hathcock, Qiwei Yu, Yuhai Tu, Nature Communications, 15, 8892, 2024.

报告人简介：

Professor Yuhai Tu graduated from University of Science and Technology of China in 1987. He came to the US under the CUSPEA program and received his PhD in physics from UCSD in 1991. He was a Division Prize Fellow at Caltech from 1991-1994. He joined IBM Watson Research Center as a Research Staff Member in 1994 and served as head of the theory group during 2003-2015. He has been an APS Fellow since 2004 and served as the APS Division of Biophysics (DBIO) Chair in 2017. He is also a Fellow of AAAS.

Yuhai Tu has broad research interests, which include nonequilibrium statistical physics, biological physics, theoretical neuroscience, and most recently theoretical foundations of deep learning. He has made seminal contributions in diverse areas including the flocking theory, growth dynamics of Si-aSiO2 interface, pattern discovery in RNA microarray analysis, quantitative models of bacterial chemotaxis, circadium clock, and the energy-speed-accuracy relation in biological systems.

For his work in theoretical statistical physics, he was awarded (together with John Toner and Tamas Vicsek) the 2020 Lars Onsager Prize from APS: "For seminal work on the theory of flocking that marked the birth and contributed greatly to the development of the field of active matter." https://www.aps.org/programs/honors/prizes/prizerecipient.cfm?last_nm=Tu&first_nm=Yuhai&year=2020