Everything we see and do is regulated by electrical signals in our nerves and muscles. The focus of my research over the last decade has been to understand how the proteins that generate and transform these electrical signals in cells actually work. Ion channels, which function like tiny pores in the cell membrane, are crucial for sensing and generating electrical signals. My laboratory uses human disease causing mutations in ion channels as a scientific “compass” to direct our inquiries into how ion channels and their molecular partners control cellular activity in neurons. Ion channel research was catalyzed by the invention of glass electrodes to measure electrical signals in cell membranes. However, the average neuron in a human brain sends electrical signals across cables or axons that are only 1/1000th the width of a human hair while also sometimes spanning a meter in length. Progress in the field of neurobiology has been stymied by the fact that the axon is far too small and delicate for measuring ion channel function with electrodes. In principle, these measurements could be achieved with light in the proper setting. Thus, my laboratory at Dartmouth College focuses on devising and refining optical techniques to measure ion channel activity at the nanometer scale within live neurons using genetically-encoded optical indicators. Combining this optical approach with rodent genetics has allowed us to discover and publish novel modulators of synaptic transmission. Our goal is to expand this area of knowledge and potentially identify critical regulators of human disease in synaptic transmission for future therapeutic avenues.measure physiological outputs from neurons using optogenetic indicators in combinations with genetic and biochemical approaches.
As such our future projects are trying to determine the following, please contact us for more details:
1) Determine how distinct regions of the axonal arborization sculpt propagating APs. 2) Determine how AP shape is coupled to neurotransmitter release at presynaptic terminals. 3) Identify the signaling mechanism(s) that engages adaptive plasticity of the presynaptic waveform. 4) Determine the mechanisms that stabilize and traffic sodium channels within the axon initial segment. 5) Identify what mechanisms couple calcium channels to synaptic vesicles.