Regulation of Protein Synthesis Initiation

My research interest is to understand the molecular mechanism of the regulation of protein synthesis initiation in higher eukaryotes. We are applying biochemical and molecular biology techniques to analyze the structure-function relationship of the translational regulators, which play important roles in the regulation of protein synthesis initiation. Currently, we are looking at the molecular mechanism of translational regulation in the following areas:

Translational regulation during serum-starved condition:

Growth factors are essential for growth and proliferation of mammalian cells. In the absence of these factors, cells shut down overall protein synthesis as a defense mechanism. We are examining in detail the molecular mechanism of inhibition of protein synthesis initiation at this condition.

Translational regulation during heat-shock condition:

Similar to growth factor deprivation, heat shock is considered as a stress condition. Mammalian cells grown 5-10 °C above normal temperature (37 °C) respond to this stress condition by shutting down the overall rate of protein synthesis. Defining the molecular mechanism of this process is our one of the goals.

Translational regulation during viral infection:

At the early stages of viral infection, there is a shut off of host-protein synthesis. Molecular mechamism of such inhibition of protein synthesis is still not clear. We intend to determine the molecular mechanism of this cellular event by understanding the details of the protein synthesis initiation during this process.

Translational regulation during skeletal muscle differentiation:

During development and wound healing quiescent cells present in the terminally differentiated muscles enter into the cell cycle to generate myocytes. The myocytes later fuse into myotubes to regenerate new muscles and tissues. We are trying to understand the molecular mechanism for this reversible phenomenon.

Cloning and characterization of translational regulators:

To understand molecular details of translational regulation in mammals, we are cloning and characterizing translational regulators by applying recombinant DNA technologies and yeast two-hybrid assays.

Translational regulation and angiogenesis:

Angiogenesis is the process of forming new blood vessels from the existing one, and it needs active translational machinery for synthesis of several cytoskeletal proteins. Several anti-cancer drugs can inhibit this process. A family of anti-cancer drugs binds and inhibits the function of a translational regulator, p67. We are studying the molecular mechanism of such binding and inhibition of its function in detail.