Principal Investigator Arup Chakraborty
Higher organisms, like humans, have an adaptive immune system that enables them to mount pathogen-specific responses to a diverse and evolving world of microbial organisms, and to establish memory of past infections. However, this very flexible system can also go awry, and many diseases are the direct consequence of the adaptive immune system failing to discriminate between markers of “self” and “non-self”. The desire to combat infectious diseases and the suffering caused by autoimmune diseases has motivated a great deal of experimental research aimed toward understanding how adaptive immunity is regulated. These endeavors have led to some spectacularly important discoveries. In spite of these major advances, an understanding of the mechanistic principles that govern the emergence of an immune or autoimmune response has proven to be elusive. An example of a practical consequence of this missing basic knowledge is the inability to design a vaccine against HIV, one of the scourges on the planet.
One important reason for the difficulty in elucidating mechanistic principles underlying adaptive immune responses is that the pertinent processes involve cooperative dynamic events with many participating components that must act collectively for a given phenomenon to emerge. Moreover, these processes span a spectrum of time and length scales. When a cell of the immune system detects the presence of foreign molecules, its activation is predicated upon signal transduction involving many proteins interacting in complex non-linear ways. Several cell types interact in tissues (such as lymphoid organs) in complex ways to orchestrate immune responses, and finally, there are collective phenomena that occur on the scale of the entire organism. Phenomena that occur on different scales influence each other. Such hierarchically organized cooperativity, with feedback between the scales, often makes it difficult to intuit underlying mechanisms from experimental observations. Further confounding intuition is that many relevant processes are inherently stochastic in character.
Statistical physics developed and impacted chemical and engineering applications in the twentieth century. It describes how macroscopic phenomena emerge from interacting and fluctuating assemblies of microscopic components. Over the last decade, our group has focused on developing and applying theoretical and computational approaches, rooted in statistical mechanics and chemical kinetics, to problems in immunology. The principal focus of our work has been various aspects of the biology of T lymphocytes, which play a central role in mediating adaptive immune responses. Our work is distinguished by its close synergy with complementary studies in experimental immunology laboratories and clinical research. We have collaborated with over 15 different immunology laboratories.