Read Lab Dynamics of Complex Biochemical Systems Read Lab Dynamics of Complex Biochemical Systems Prof. Elizabeth Read Assistant Professor B.A. Chemistry and Mathematics, University of Colorado (2003) Prof. Elizabeth Read Assistant Professor B.A. Chemistry and Mathematics, University of Colorado (2003) Key Publications: 1.“Stochastic effects are important in intra-host HIV evolution even when viral loads are high,” E. L. Read, A. A. Tovo-Dwyer, A.K. Chakraborty (in press, Proc. Natl. Acad. Sci.). 2.“Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection ” A. Kosmrlj*, E. L. Read*, Y. Qi, T. M. Allen, M. Altfeld, S. G. Deeks, F. Pereyra, M. Carrington, B. D. Walker, A. K. Chakraborty Nature 465 (2010) 350–354. Key Publications: 1.“Stochastic effects are important in intra-host HIV evolution even when viral loads are high,” E. L. Read, A. A. Tovo-Dwyer, A.K. Chakraborty (in press, Proc. Natl. Acad. Sci.). 2.“Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection ” A. Kosmrlj*, E. L. Read*, Y. Qi, T. M. Allen, M. Altfeld, S. G. Deeks, F. Pereyra, M. Carrington, B. D. Walker, A. K. Chakraborty Nature 465 (2010) 350–354. Research Summary: The immune system is a vast network of cells, proteins, and chemical messengers that monitors signs of disease and defends the host against perceived threats. The complexity of these processes—they are multi-scale, nonlinear, and subject to randomness at the molecular level—means that computer models are vital for uncovering mechanistic principles based on varied experimental data. In the Read lab, our goal will be to elucidate immune system dynamics and regulation through theory and simulation of the biochemical reaction networks underlying immune functioning. A major focus will be predicting interventions that can alter immunological behavior in order to treat or prevent disease. Specific areas include: 1. Regulation of T cell immunity. T cells (essential players in immune responses) become ineffective after chronic stimulation. Elucidating how the immune system balances positive and negative signals will identify strategies for reversing T cell dysfunction in chronic infections and cancer. 2. Selection of targets by the immune system. An immune response is often mounted against a small subset of pathogenic molecular signatures, out of many potential targets. Determining what controls this selection process will have applications for vaccine design. 3. Escape from immunity. Many viruses and tumors readily mutate to escape immune responses. We are investigating how immune pressure shapes fitness landscapes and drives evolutionary dynamics and disease progression. 4. Transition paths in complex systems. Understanding how the immune system processes information and transitions between states requires advanced computational tools to treat complex, stochastic dynamics. We will develop efficient path-sampling tools for applications in multi-scale biological systems. Research Summary: The immune system is a vast network of cells, proteins, and chemical messengers that monitors signs of disease and defends the host against perceived threats. The complexity of these processes—they are multi-scale, nonlinear, and subject to randomness at the molecular level—means that computer models are vital for uncovering mechanistic principles based on varied experimental data. In the Read lab, our goal will be to elucidate immune system dynamics and regulation through theory and simulation of the biochemical reaction networks underlying immune functioning. A major focus will be predicting interventions that can alter immunological behavior in order to treat or prevent disease. Specific areas include: 1. Regulation of T cell immunity. T cells (essential players in immune responses) become ineffective after chronic stimulation. Elucidating how the immune system balances positive and negative signals will identify strategies for reversing T cell dysfunction in chronic infections and cancer. 2. Selection of targets by the immune system. An immune response is often mounted against a small subset of pathogenic molecular signatures, out of many potential targets. Determining what controls this selection process will have applications for vaccine design. 3. Escape from immunity. Many viruses and tumors readily mutate to escape immune responses. We are investigating how immune pressure shapes fitness landscapes and drives evolutionary dynamics and disease progression. 4. Transition paths in complex systems. Understanding how the immune system processes information and transitions between states requires advanced computational tools to treat complex, stochastic dynamics. We will develop efficient path-sampling tools for applications in multi-scale biological systems.