Genome-wide association studies have identified hundreds of loci associated with addiction and other behaviors, but understanding the mechanism of action of the vast majority of those loci has remained elusive. The Pfenning laboratory has developed a new set of methods to link those loci to conserved cell type-specific regulatory function. First, single cell open chromatin experiments from the striatum are used to train machine learning models that can predict cell type-specific enhancers from genome sequence. We combine those models with new comparative genomic methods and 222 mammalian genomes to predict the cell type-specific function of genetic variants associated with addiction, Alzheimer’s disease, and other neural traits. To follow up on those predictions, we have developed a reporter assay technology that can measure the regulatory activity of hundreds of candidate enhancers in one experiment. Finally, we are leveraging our regulatory models to screen for enhancers that will label specific neuron subtypes in downstream experiments. Surprisingly, our research has implicated rare neuron subtypes, including D1-D2 hybrid neurons of the striatum, as playing a central role in mediating the predisposition to addiction behavior.

Presenter: Andreas Pfenning, PhD
Assistant Professor, Computational Biology Department, Carnegie Mellon University

Where: Hybrid Event

• In person: Nelson Biology Laboratories Building – Busch Campus – Room D406
  604 Allison Road, Piscataway, NJ 08854
• Virtual: https://rutgers.zoom.us/j/99533254531?pwd=cXMvaGw3K21tdEVXdmNWOW1xbnRQZz09