Intercellular Communication
in the Adaptive Immune System

Professor and Chairman Arup K. Chakraborty
Department of Chemical Engineering, Department of Chemistry
Biophysics Graduate Group,
University of California, Berkeley

Date: Thursday, February 10, 2005
Time: 4:00 p.m.
Place: Engineering II, Room 3361

ABSTRACT

Higher organisms, like humans, have an adaptive immune system that can respond to pathogens that have not been encountered before. T lymphocytes (T cells) are the orchestrators of the adaptive immune response. They interact with cells, called antigen presenting cells (APC), which display molecular signatures of pathogens on their surface. T cells detect the presence of these molecular signatures of pathogens with great sensitivity. How T cells discriminate between “self” and “non-self” with extraordinary sensitivity, and how intracellular signaling leading to commitment to activation is regulated are central questions in fundamental biology. Answering these questions will also aid the development of intervention protocols for a host of diseases. I will discuss recent work where synergy between theory and computation (rooted in statistical mechanics) and genetic, biochemical, and imaging experiments have shed light on certain aspects of the pertinent issues.

Contemporary analytical techniques can, given sufficient time and resources, detect trace amounts of almost any analyte. In contrast there exists no general solution to the problem of analyte detection in settings, such as civil defense and in the developing world, where speed, cost and convenience are critical constraints. In order to meet these challenging goals we are developing optical and electronic biosensor platforms based on the binding-induced folding of peptides, proteins and DNA. Our protein folding-based optical sensors provide a rapid, sensitive detection architecture generalizable to a wide range of macromolecular analytes. Our analogous electronic DNA sensor is reagentless, reusable, highly miniaturizable and combines picomolar sensitivity with greater than million-fold selectivity. The sensitivity, gain and background suppression of these folding-based sensors suggest that they may provide a means for the inexpensive and operationally convenient detection of a wide range of clinically, defense and environmentally relevant materials.