Information processing and regulation in biological networks.
To survive in an unpredictable world, both bacterial and higher organisms have evolved complex biological networks which enable reliable sensing and transmission of extracellular information from environment to a set of target genes. External information can be stored and trasnmitted in cells via wide variety of mechanisms which include epgienetic modifications, allosteric binding or via non-linear relationships in the regulatory networks. Given the molecular complexity of intracellular environments the speed, accuracy and robustness of the information flow in cells appears baffling. Our group is using thereotical concepts and computational techniques drawn from the fields of stochastic dynamics, non-linear physics and information theory to uncover principles of functional regulation and information processing in biological networks. In particular we are interested in problems of gene regulation and fate determination in eukarypoic gene networks. The work we have done has generated novel insights into mechanistic principes of operation of pluripotency network of mouse embryonic stem cells and core regulatory network of mammalian imune response.
Self-assembly of biomolecules and active matter
Regulation of genetic information often relies on formation and dissolution of bio-molecular assemblies with high speed and specificity. These bio-molecular assemblies can consist of transcription factors bound with multiple proteins and/or RNA/DNA molecules. Due to the large molecular sizes, multiplicity of folding and binding modes and the relatively small pool of available crystal structures, many molecular level mechanistic questions about these assemblies remain unclear. An outstanding question is how multiple proteins work in a concerted manner with the partnering proteins and nucleic acids in order to function as allosteric switches or for enhancing affinitiu/specificity of binding. To this end we build and deploy predictive coarse-grained models based on energy landscape theory to work out various mechanicstic problems in biomolecular assembly.
Meso-scale stochastic reaction dynamics and transport in heterogenous cellular environments
Biochemical reactins in living cells take place in crowded and active environments which can have considerable imapact on the diffusive transport, phase separation and reaction dynamics of biomolecules. In many instances the familiar kinetic models based on mean field descriptions can break down thereby necessitating more rigorous treatment of molecular heterogeniety in the environment. We are interested in exploring such complex situations by employing combination of brownian dynamics, finite element and patially resolved hybrid stochastic dynamics modeling. The goal of this research is to disentangle the roles of structured and dynamic environemntal forces on the biochemcial reaction kinetics and transport of biomolecules.