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 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 the immune response to flu proteins. Using coarse-grained molecular dynamics simulations and modeling the immune response, we show that nanoparticles presenting flu proteins at unique geometries and densities can direct the immune response, and lead to the creation of antibodies of high breadth. These can form the basis for a universal flu vaccine.