Speaker: Fangzhou Xiao, Ph.D., Assistant Professor in Engineering, Westlake University, Principle Investigator of the Biomachine Architecture and Control (BMAC) group

Time: 11:00-12:00 a.m., March 28, 2024, GMT+8

Venue: B101, Lui Che-woo Building, PKU 

Abstract: 

The robust yet versatile behaviors of biological organisms act via biomolecular processes in cells that happen through catalysis by enzymes. To regulate the rate of these processes, substrates, regulator proteins, cofactors, and other helper molecules bind with the catalytic enzyme to change its activity. Existing methods to analyze regulation of catalytic processes require simplifications by over-abundance assumptions, exemplified by the Michaelis-Menten formula. However, recently uncovered complex regulatory circuits with combinatorial or highly dynamic behaviors in metabolic engineering and developmental and synthetic biology break these assumptions. This imminent future of science and engineering on biological systems calls for a method to capture the full regulatory profile for holistic analysis, without restrictive assumptions. In this talk I will show a novel foundation of bioregulation based on an analysis of binding networks using differential geometry and convex polyhedra that captures bioregulation holistically in terms of reaction order polyhedra (ROP). ROP can be tractably analyzed and scalably computed for arbitrary binding networks. I will also show how this new foundation constitutes a rule of life, flux exponent control (FEC), that enables a radically new method to model metabolism dynamics via optimal control. FEC can capture fast metabolism dynamics on the timescale of seconds to hours that are previously inaccessible to the state-of-the-art method, flux balance analysis. FEC can predict dynamic features emerging directly from metabolic network stoichiometry, e.g. glycolytic oscillations and cell growth arrest from shocks. Looking into the future, ROP and FEC form a holistic and dynamic foundation for bioengineers to analyze and design system level architectures governing cellular dynamics, with applications ranging from metabolic engineering, gene regulatory circuits, cell survival and growth, and microbial communities.

Source: Academy for Advanced Interdisciplinary Studies, PKU