Understanding the Molecular Mechanisms of Pathogen Recognition by the Immune System: Biothreat Reduction through Predictive Science

LDRD-DR, Byron Goldstein (PI)

Cells are exquisite detectors, constantly monitoring their environment through the use of cell-surface receptors. Building predictive models of the events triggered when cells are exposed to external stimuli such as toxins or pathogenes is one of the grand challenges for cell biology and predictive science. Inb a joint experimental-theoretical effort we will develop predictive models of signaing cascades initiated by receptors that regulate the body's defenses against infection. Understanding how cells detect and respond to pathogens is critical for understanding how naturally occuring or man-made pathogens circumvent the body's defences and for developing strategies to counter infection and reduce biothreats.

Receptor Aggregation and Its Effects

NIH/NIGMS, Byron Goldstein (PI)

Mobile receptors diffusing over the surface of a cell allow it to sense its environment and respond to it. For many types of receptors, including the multisubunit immune recognition receptors (MIRR), aggregation of these receptors is crucial for the capture of external ligands and mandatory for the turning on or off of cellular responses. The project focuses on the high affinity receptor for IgE, FceRI, and MIRR that plays a key role in allergic reactions. A major goal of this project is to build and test detailed models of the early events of cell sinaling mediated by this receptor. The mathematical models will be used to analyze experimental data, determine parameter values, design new experiments and test ideas about the roles of specific signaling molecules and their subunits.

Design Principles of Genetic Regulatory Networks

LDRD-ER, Michael Wall (PI) and William Hlavacek (Co-PI)

Our goal is to discover design principles of genetic regulatory networks through an integrated theoretical and experimental approach. We aim to address two questions regarding binary gene circuits, in which two transcriptions factors jointly regulate gene expressions: Are there rules that govern regulatory interactions in binary circuits with a feed-forward loop? What are the functional differences between binary cascaded circuits and unary circuits?

Mathematical Modeling of Signal Transduction by a TIR Receptor, a project within the Center for Evolutionary and Theoretical Immunology

NIH/NCRR, William S. Hlavacek (PI)

Metabolomic Functional Analysis of Bacterial Genomes

OE/OBER, Clifford J. Unkefer (PI)