What happens in the body when a person smokes a cigarette? What happens after several weeks of smoking? Why do dopaminergic neruons degenerate when people develop Parkinson's disease? And why does smoking appear to lower the probability of a person developing Parkinson's disease? The Lester lab uses techniques at the intersection of biophysics, single-molecule imaging, chemistry, mouse genetics, and neuroscience to understand the biophysical basis of ligand-gated ion channels including the nicotinic acetylcholine receptor.
Recently our lab has shifted from focusing on the immediate effects of nicotine binding to receptors on the surface of nerve cells to what happens when that nicotine infiltrates deep into the cell. Nicotine receptors entering the endoplasmic reticulum increase its output of these same nicotine receptors which then travel to the cell's surface. In other words, nicotine acts "inside out," directing actions that ultimately fuel and support the body's addiction to nicotine. These longer-term changes deep within the cell may also explain why the beneficial actions of antidepressants and antischizophrenic drugs require several weeks to develop.
