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Evolution and immunology of pathogens


Pathogens evolve rapidly to circumvent drug treatments and immune surveillance, which dramatically impacts public health. The treatment is complicated by high genetic diversity of some viruses within and across infected individuals, as well as their complex evolutionary mechanisms, including selection, random genetic drift, and temporal variation in a host environment. Moreover, many pathogens have a large number of linked sites that evolve simultaneously and inter-dependently through two different effects, "epistasis" due to interaction between proteins and signaling network, and co-inheritance linkage ("clonal interference").  The last decade has seen explosive progress in mathematical modeling of microbial populations and high-fidelity sequencing. 

Taking advantage of these developments, we address the evolution of microbes and viruses (HIV, influenza, polio,  Zika, and others). Previous research of the group leader focused on developing mathematical tools that predict evolution of pathogens with strong linkage effects, including analytic and computational methods and estimators of evolutionary parameters from viral sequence data. Launching from these studies, we are applying existing methods and models to study the viral evolution under time-dependent conditions, develop new mathematical techniques and improve existing phylogenetic tools. Our multi-disciplinary team fuses the recent mathematical discoveries with multiple-scale modeling and software tools. We are especially interested in the evolutionary effects and signatures of epistasis, genetic recombination, and in the theory of phylogenetic relationships in the presence of selection and the other factors of evolution. The project is designed to create significant clinical impact by fostering research into novel classes of drugs to control viral adaptation rate and achieve viral containment. Our software will facilitate personalized medicine and vaccine design against the pathogens escaping treatment and immune responses. The results are published and diffused in higher education and public presentations.

Selected Publications