Title: Geometry and stochastic dynamics in biological systems
The interaction of proteins with chromatin regulates many cellular functions. Most DNA-binding proteins interact both non-specifically and transiently with many chromatin sites, as well as specifically and more stably with cognate binding sites. These interactions and chromatin structure are important in governing protein dynamics. I will show that the dynamics of proteins is determined by the 3d organization of chromatin in the nucleus.
By analyzing the motion of CTCF, a zinc-finger DNA binding protein observed using microscopy methods, we found that it interacts with a new type of small nuclear domains. These domains, composed of RNA, are central in guiding CTCF to find its cognate binding site and in determining the organization of chromatin.
In the second part of the talk, I will describe our advances in studying antibodies development against flu proteins. Using coarse-grained molecular dynamics simulations and a population-dynamics model of the adaptive immune system, we study the immune response to nanoparticles presenting flu proteins at unique geometries and compositions. We show that these nanoparticles can direct the immune response in distinct evolutionary paths, and elicit the creation of antibodies of high breadth - capable of neutralizing multiple flu strains. These nanoparticles could form the basis of a universal flu vaccine.