LC Seminar- Jianhua Xing
April 4th @ 12pm in LC 101
Complex Biology, Simple Physics
“Studying biological physics in the big data era”
Jianhua Xing, University of Pittsburgh
Abstract:
Seemingly complex biological processes are often governed by simple physics principles. For example, cooperativity plays an important role in various biological processes as in physics. I will present examples in explaining epigenetic memory (Zhang PRL 2014), the intriguing Nobel-Prize winning puzzle of olfactory receptor selection (Tian PNAS 2016), coordinated gene regulation during cell fate change (Zhang Plos Comp Biol 2019), and focus on our recent study on chromosome folding.
How a polypeptide (with ~ 300 monomers) folds into a protein has been a century problem and attracts enormous public attention with the advent of AlphaFold. It is a more challenging problem how chromosomes (with up to ~10^8 monomers and a total length ~ 2 meters for 46 human chromosomes) fold and form segregated territories within a nucleus with size ~ 10 microns or less. Based on an original work of de Gennes, a dominating model is that chromosomes fold into a crumpled state, which explains experimental data up to 5M bp, only deviates at intermediate range due to formation of loops (within 1kb or less), and the latter is explained by a loop-extrusion model. However, from analyzing HiC and chromosome tracing by DNA FISH, we identified unexpected highly conserved structures formed by genomic regions separated by 100M bp or further. Our (2-10) hour-long CRISPR-dCas9 guided live-cell imaging confirmed that the structures are stable. Statistical analyses reveal the structures are stabilized through cooperative binding. Our work suggests a highly robust mechanism for chromosomes to fold through coordination of mechanisms at three scales: the identified structures reduce the state space and facilitate formation of crumpled state and short-ranged loops.
If time allowed, I will also briefly mention our efforts of reconstructing equations of motion for cellular processes. One message I would like to convey from my talk is that physical intuition is important even in the time of big data era.
