Intracellular Signalling

Our team is interested in deciphering the inner workings of the Ras/MAPK signalling pathway using Drosophila genetics in conjunction with molecular and biochemical approaches. The small GTPase Ras plays a central role in the control of cell proliferation, differentiation and survival by mediating signals elicited by membrane receptors, such as receptor tyrosine kinases (RTKs), to distinct downstream effector pathways.

Ras was first identified as the transforming agent of the Harvey and Kirsten mouse sarcoma viruses, which led to the identification of the three mammalian genes, H-, K- and N-Ras, encoding nearly identical molecules. The subsequent finding that activating mutations in Ras is one of the most frequent genetic lesions associated with tumor formation in humans has stimulated much interest to elucidate the role of Ras in normal and malignant cells. Several Ras effector pathways have been identified to date including the so-called “classical” and evolutionarily conserved MAPK pathway that is one of the main routes used by Ras to transmit its proliferative and differentiation signals.

We use genetic, biochemical and functional genomics approaches in Drosophila in order to characterize specific Ras/MAPK signaling events. Our work currently focuses on three themes: 1) mechanisms regulating Ras-dependent RAF dimerization leading to RAF kinase activation, 2) coordination and regulation of Ras/MAPK signalling processes through scaffolding proteins; 3) regulation of MAPK protein levels and its influence on Ras/MAPK signalling.

In addition, we use Drosophila as an experimental tool for identifying and characterizing modulators of leukemia-causing oncogenes.

Follow IRIC

Logo UdeM