The Chesler Lab

Researches the genetics underlying behavior and identifies relationships among behavioral traits.

MY RESEARCH FOCUS

My research emphasizes the integration of genetic, genomic and phenomic resources to improve the ways in which behavioral traits in mice are associated with complex underlying genetics and genomics. I integrate genetic and genomic findings in model organisms including the laboratory mouse with data on human behavioral disorders using novel computational tools and approaches developed in my laboratory.

To this end, my lab has developed GeneWeaver.org in close collaboration with computer scientists at the University of Tennessee and Baylor University. This system allows users to integrate heterogeneous phenotype-centered gene sets across species, tissues and experimental platforms. This publicly available tool uses fast combinatorial algorithms to infer the latent ontology of behavior from the sets of genes and phenotypes developed using large empirical data sets. It provides a unique resource for investigators in many areas of biological science to integrate data that is typically lost to further analysis. The use of this system has led to the identification of several genes and polymorphisms underlying behavioral variation, and it can be used to ensure that mouse models are relevant to the human clinical state to achieve greater precision in identifying the genetic, environmental and life-history contributions that shape behavior.

Our other research efforts center on the development and application of genetic reference populations for the systems genetic analysis of behavior, including the Collaborative Cross and Diversity Outbred populations. These studies reveal underlying factors of behavior in laboratory mice, and the co-expressed genes associated with each behavior. We continue to analyze this tremendous wealth of data to understand the relations among behavioral traits and to identify novel candidate genes for complex behaviors, many of which are related to vulnerability to drug and alcohol use.

Full Scientific Report

Advanced mouse populations

Behavioral variation in the widely used laboratory mouse strains has been historically limited. New high-diversity mouse resources exhibit an expanded behavioral repertoire and provide phenomenal opportunities for investigation of the genetics of behavior. My group performs genetic and behavioral characterization of the Collaborative Cross and Diversity Outbred populations, novel mouse resources that randomize the genetic diversity found among inbred mouse strains. My group, previously at the Oak Ridge National Laboratory, played a critical role in generating and characterizing this population, which has now given rise to the mature Collaborative Cross population at University of North Carolina and the Diversity Outbred at The Jackson Laboratory. Our genetic analyses demonstrate the high precision and accuracy of these new populations for genetic research, which will enable the deep discovery of biological mechanisms of behavioral variation.

The Collaborative Cross and Diversity Outbred populations provide unique opportunities for the study of behavior due to the tremendous diversity among their founder strains. This has provided remarkable behavioral variation, which had been selected out of the common inbred populations. Our recent work in the Center for Genome Dynamics has revealed high precision genetic loci for behavioral traits in this population, and high-precision genomic networks. This precision will allow us to more precisely relate behavioral variation to biological processes, and to refine the classification of behavioral traits.

Our research necessarily relies on advancing capabilities in high-throughput experimentation, data integration and public data dissemination. Members of my laboratory are involved in the Knockout Mouse Phenotyping program (JAX KOMP2) a project of the International Mouse Phenotyping Consortium, and the JAX Nathan Shock Center on the Basic Biology of Aging.

Outreach and education promote a greater understanding of scientific exploration. My laboratory performs a variety of outreach activities including the development of the LEGO Behavioral Lab designed to provide students and integrative educational experience in the technology and concepts in behavioral science research. Members of my lab actively participate in other science educational activities in the Mount Desert Island Regional School System and local community.