Research in this area involves construction of mathematical models for specific biological processes/pathways, carrying out computer simulations for specific questions/situations/experiments, and analyzing the simulation results to see whether the modeling offers additional insight into the biological process being studied. Most of these studies are carried out in collaboration with experimental biologists, and so 'ownership' of individual projects rests mostly with the collaborators. A few ongoing projects are:
Autogeneous TBP regulation
The protein TBP is thought to be required for its own synthesis (in addition to being required for transcription of most genes). It dimerizes, but the dimer is incapable of binding to DNA. In order to study the autocatalytic dynamics and the role of dimer formation in the process, a mathematical model was constructed and simulated under parameters corresponding to several physiological conditions. A paper (Gokhale et al, 2010) reporting part of this work is available here.
Collaborator: Beena Pillai, IGIB, New Delhi
Modeling the effect of training on neuronal responses
Neurons, whether as part of the brain or in vitro, show differing responses to the same test input signal depending on the previous training signals. For instance, neurons 'remember' information from spaced signals better than from massed signals, and exhibit long-term potentiation or depression depending on the amplitude and frequency of the training signals. We are interested in identifying the minimum intracellular signaling network in the post-synaptic neuron that has these properties.
Modeling signal transduction
We have worked on modeling growth factor associated signaling as part of the CSIR Systems Biology project. The goal was to be able to model large signal transduction pathways and use the models to predict potential targets of multi-target therapeutic agents. We have worked on modeling to understand the effect of sumoylation on NFkB signaling.
Collaborator: Girish Ratnaparkhi, IISER-Pune
Modeling for synthetic biology
There are two sub-projects:
1. Modeling the effects of synthetic additions to existing pathways: This research is was part of the CSIR synthetic biology project. The aim is to predict the effect of inserting one or many 'foreign' genes into a microbial genome in terms of the intracellular concentrations of the gene products as well as the components of the metabolic pathways that are affected by the reactions catalyzed by the foreign genes.
2. Designer biology: The goal is to computationally analyze the potential behavior of regulatory circuits that are designed and incorporated in host cells. This was part of Bharat's PhD research. Bharat has written a nice review on regulatory circuits in neurons, available here, and studied the dynamics of several regulatory motifs.
Collaborators: Beena Pillai, IGIB; K. V. Venkatesh, IITB