Sandra Rosenthal, PhD
Elucidating Molecular Mechanisms of Mental Illness with Ligand Conjugated Nanocrystals
Director, Vanderbilt Institute of Nanoscale Science and Engineering
Jack and Pamela Egan Professor of Chemistry
Professor, Physics, Pharmacology, and Chemical and Biomolecular Engineering
The need to create quantitative mental heath diagnostics, improve and personalize treatments, and ultimately find cures to mental illness is both urgent and overwhelming. Statistics, which tell a disturbing story, include:
For the past 15 years we have been developing a novel approach to study transporter proteins that regulate the neurotransmitters serotonin and dopamine, which are out of balance in mental illness. These transporter proteins are targeted by the majority of antidepressant medications. We chemically attach fluorescent nanocrystals (quantum dots) to the transporter proteins via a drug linker in order to make movies of the motions of the protein. Nanocrystals are incredibly bright and do not photobleach, thus it is possible to observe the motion of the protein for a prolonged period. We learned from these quantum dot protein tracking experiments, as one example, that serotonin transporter proteins exist in two populations, one that is mobile and one that is restricted. Further, when the protein is activated so that it takes up more serotonin (this would be “pro-depressive”) the protein becomes much more mobile. For the first time, we established a link between mobility of the transporter protein and its function. Time and protein mobility are variables that must be considered when trying to understand depression at the molecular level. A second example that will be discussed is differences in protein mobility in a mutation of the dopamine transporter that is linked to attention-deficit/hyperactivity disorder. The development and optimization of ligand conjugated quantum dots will also be presented.