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My name is Dhruv K Pant, I am a post-doctoral fellow in Dr. Ghosh's
group in the physics department. My research comprises of applying
numerical methods to try and get a better understanding of the
dynamics in the development of cancer. We do this by investigating
signal transduction in cells of experimentally well studied pathways,
such as the MAPK pathway, involving known oncoproteins such as Ras,
Raf etc. It is believed that tumor growth occurs not through a single
mutation in a protein but in a more complex manner through cumulative
mutations along the signaling pathway. It is our aim to quantify and
rank the key mutational points in the signaling pathways. We use a
kinetic model and two methods, a searching algorithm and the
numerically simpler linear response method to systematically identify
tumor suppressors, proto oncogenes and other mutation events(such as
expression levels), in the network of pathways included in the model
which can lead to undifferentiated cell growth.
One of the ways oncogenesis is characterized is by high levels of activated ERK in the cell even in the absence of the growth factor EGF. The analysis is done using chemical kinetics. This involves solving a large number of coupled ordinary differential equations (corresponding to the various reactions occurring in the cell, viz. enzymatic, association and disassociation reactions, with the experimentally derived rate constants ) to obtain the temporal behaviour of the proteins/enzymes we are interested in. Future work would include the effects of diffusion and compartmentalization in the cell as part of the analysis, using estimated rate constants which give the best fit to the experimental data. Identifying the key oncogenes and the cumulative mutations involved will then enable us to target these sites/enzymes to inhibit the process of oncogenesis. |