Clarissa Parker from Middlebury College has been awarded a research grant from the National Institute on Drug Abuse through NIH’s R15 Academic Research Enhancement Award (AREA) program. The grant provides three years of funding to support a project titled “Genome-Wide Association for Affective Withdrawal in Outbred Mice.” The goal of this work is to use a highly recombinant mouse population to map genes in mice associated with the behavioral and physiological traits that characterize drug withdrawal. Her underlying hypothesis is that mouse genes involved in amphetamine withdrawal, or other members of their genetic networks, may influence drug use disorders in humans and may provide novel targets for pharmacologic intervention.
Negative mood states that characterize drug withdrawal are partly under genetic control and have been associated with craving and relapse to drug use in humans. Mice can be used to model aspects of the negative mood states associated with drug withdrawal and offer a powerful tool for elucidating the genetic architecture of both diseases and normal behavioral and physiological traits. However, genomic studies in mice have lagged behind those in humans. Genome-wide association studies identify genes associated with diseases and other traits---and have revolutionized the field of human genetics. Unfortunately, progress in mouse genetics has been less sucessful. This is because mouse genetics has traditionally focused on crosses between inbred strains that make it difficult to pinpoint specific genes associated with a trait. Dr. Parker’s method takes advantage of the superior mixing that is present in outbred mouse populations to identify genes using two steps: genotype-by-sequencing, which sequences about one percent of the mouse genome; and RNA sequencing, which identifies only genes turned “on” in a particular tissue, such as the brain.
This project will facilitate student research at Middlebury College by providing summer salary for six students conducting research in Parker’s laboratory. Approximately two to four additional students will work on components of the proposed experiments for course credit each year (theses or smaller projects). In the process of accomplishing this goal, Middlebury students will obtain meaningful training in the discipline of behavioral genetics, learn cutting-edge molecular and quantitative genetic techniques, utilize mice as models of psychiatric disorders, and gain a deep understanding of the neurobiology underlying drug use disorders.
Importantly, the methods proposed in Dr. Parker’s grant are generally applicable to any quantitative trait and have the potential to vastly accelerate the process of gene identification. If one understands the pathways linking genetic variation and expression to neuronal function and behavior in mice, then it may be possible to target specific molecules to prevent and treat drug use disorders in humans.