Ricardo E. Dolmetsch
Changes in cytoplasmic calcium play a central role in converting electrical events at the cell membrane into the activation of enzymatic cascades in the cytoplasm of cells. We are interested in understanding how intracellular calcium activates the signalling pathways that regulate the survival, motility and morphology of neurons and muscle cells. One of the main projects in the laboratory is to identify the full set of proteins that are associated with voltage gated calcium channels using a variety of proteomic approaches. In parallel we are characterizing the function of specific channel-interacting proteins using a multidisciplinary approach that includes digital calcium imaging, electrophysiology, in vitro cell biological assays and genetically engineered mice. We are also searching for small molecules that disrupt the interaction between calcium channels and their associated proteins as a way of developing new pharmaceuticals that modulate calcium signalling.
A second project of the laboratory is to determine how different temporal and spatial patterns of cytoplasmic calcium regulate the expression of genes in the nervous system. We are developing ways of profiling gene expression in single neurons stimulated with defined patterns of intracellular calcium that are associated with cell differentiation and plasticity in the nervous system.
A final interest of the laboratory is to develop new ways of manipulating and visualizing intracellular signalling cascades in neuronal circuits. We are engineering methods to rapidly degrade specific signalling molecules in intact animals and we are developing methods for observing biochemical events in the whole tissues. Together with our studies of calcium signalling, these new technologies will advance our understanding of neuronal function and provide new treatments for neurological and cardiovascular diseases.