Genetic circuit architectures underlying cell-fate choices for immunity

Title: Genetic circuit architectures underlying cell-fate choices for immunity

Aaron Dinner, University of Chicago

Understanding how proteins contribute to biological regulation requires elucidating the collective dynamics of a network of molecular interactions.

In the first part of this talk, I will focus on a gene regulatory network in B lymphocytes that processes antigen receptor signal strength; quantitative modeling reveals how this network leads to an unusual developmental trajectory that transiently promotes receptor affinity maturation and immunoglobulin class switching before leading to terminally differentiated antibody secreting plasma cells. Beyond enabling competing demands of humoral immune responses to be balanced, the network architecture studied here provides a general mechanism for quantitative variations in a signal to be translated to a binary choice involving transient expression of one of the two developmental states.

In the second part, I will describe an analysis method that exploits natural cell-to-cell variations to substitute for artificial manipulations for inference of regulatory synergies. These studies have further motivated the development of novel algorithms for treating systems far from equilibrium, which we are now also applying to a wide range of systems.