"Constructing MyoD Interactome Networks"
Rhabdomyosarcoma (RD), one of the most common solid tumors of childhood, is believed to arise as a result of a regulatory abnormality of the growth and differentiation of myogenic precursor cells. Despite the expression of myogenic bHLH proteins of the MyoD family, RD cells fail to withdraw from the cell cycle and are unable to differentiate into muscle cells. My hypothesis is that the MyoD-associated protein complexes in the RD muscle cancer cell line are different from the complexes in normal differentiating muscle cells. The objective of this proposal is to apply dynamic mathematical models to extract and explore MyoD-associated transcriptional complexes from large-scale, multi-dimensional interactome data sets and to monitor and compare perturbations in protein interaction networks of MyoD complexes between proliferation and differentiation states in normal and RD cancer cells.
The Specific Aims are:
I) Construction of global MyoD interactome network reflecting an active regulatory circuit;
II) Establishment of an initial network boundary using pre-existing known MyoD interactions and a simplified model system.