NSF-ANR: Physics of chromosomes through mechanical perturbations

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

DNA molecules are not only carriers of genetic information but are also exceedingly long polymers. These polymers (chromosomes) are fascinating physical systems with quenched disorder, complex topological properties, and driven far from equilibrium by active processes. In this project the investigators will examine the Physics of Chromosomes by integrating approaches of theoretical and experimental biophysics of two leading groups with complementary expertise in Physics of Living Systems. The Coulon lab, at CNRS Paris, has pioneered the use of mechanical perturbation of chromosomes by moving a genomic locus within a living cell by external magnetic field. Such perturbations are methodologically novel and can provide unique information about the physical state and dynamics of chromosomes. Gaining insights from these measurements requires development of physical models of chromosome organization. The Mirny lab, at MIT, has been developing polymer models of chromosomes aiming to understand principles and mechanisms underlying chromosomes folding. The Coulon and the Mirny labs have been collaborating on this project and have published the first paper that provides extensive Preliminary Data in support of this project. Current understanding of chromosome organization is largely based on data obtained through non-perturbative experiments. The ability to apply forces and mechanically manipulate chromosomal loci in a living cell provide a unique handle to answer long standing –but yet unanswered– questions: i) What is the physical nature of chromatin? ii) How strong are molecular forces in the chromatin? iii) What mechanism underlies maintenance of chromosomal territories? This theory-driven mechanical probing of chromosomes will allow understanding of the material nature of chromosomes and uncovering new physical mechanisms underlying chromosome organization and dynamics. This project will pursue outreach activities that include Public lectures in Boston and région Île-de-France given jointly by Mirny and Coulon; development of a children's book on physics of chromosomes and the nucleus, jointly with Actin Art association and the ‘Esprits Curieux’ initiative of the Institut Curie; and the involvement of high school students in research through MIT PRIMES program. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.