Associate Professor at Wesleyan University
The regulation of gene expression is essential for organismal form, function and fitness. Understanding the genetic and molecular mechanisms responsible for regulatory divergence should therefore provide insight into trait evolution. Using deep-sequencing, we quantify total and allele-specific mRNA expression levels genome-wide within and between species of Drosophila fruit flies using custom bioinformatics pipelines developed by members of the group. This work takes advantage of the numerous qualities that make Drosophila a great system including sequenced genomes, a wealth of resources and tools and the ability to cross different species to make hybrids needed for these analyses. Using these approaches we are studying how the environment, evolution, mutations, epigenetics, development, tissue-specificity and genetic interactions influence the expression of genes genome-wide.
One major question in biology today is how to identify the genetic differences that give rise to the great phenotypic diversity we observe on Earth. To begin to explore this question we are focusing on a recently acquired adaptive trait in Drosophila sechellia, an island endemic species of fruit fly native to and restricted to the Seychelles islands. Unlike its generalist sister species (D. simulans, D. mauritiana, and D. melanogaster ), D. sechellia has evolved to specialize on a single host plant, Morinda citrifolia. Specialization on M. citrifolia is interesting because the fruit of the plant contains secondary defense compounds, primarily octanoic acid (OA), that are lethal to all other Drosophila species. Although ecological and behavioral adaptations to this toxic fruit are known, the genetic bases for evolutionary changes in OA resistance are not. Our goal is to understand the molecular basis of D. sechellia host specialization by identifying the genes responsible for D. sechellia resistance to OA toxicity.
The rate of transcription is determined by the combinatorial control of numerous transcription factor (TF) proteins that bind to linked cis-regulatory sequences in a gene called enhancers that contain TF binding motifs. Cooperatively, these TFs act as activators or repressors to modulate the expression of the focal gene. Each gene is tightly controlled by complex and highly interconnected regulatory networks. The study of regulatory networks typically defines the edges in these networks by chromatin immunoprecipitation of DNA bound by TF followed by high-throughput sequencing (ChIP-seq). Using this approach, researchers have begun to define regulatory network structure by the association of TFs with the sites on each gene’s cis-regulatory sequences to which they bind. While much progress has been made in defining genome-wide gene regulatory networks in many model systems using ChIP-seq experiments, very little is known about how information flows through these networks. We are now investigating TF-target relationships in the yeast Saccharomyces cerevisiae.
Regulatory divergence in Drosophila revealed by mRNA-seq
C . Joel McManus, Joseph D. Coolon, Michael O. Duff, Jodi Eipper-Mains, Brenton R. Graveleyand Patricia J. Wittkopp
Click HERESources of bias in measures of allele-specific expression derived from RNA-seq data aligned to a single reference genome
K raig R Stevenson, Joseph D Coolon & Patricia J Wittkopp
Click HERETempo and mode of regulatory evolution in Drosophila
Joseph D. Coolon, C. Joel McManus, Kraig R. Stevenson, Brenton R. Graveley and Patricia J. Wittkopp
click hereCaenorhabditis elegans Genomic Response to Soil Bacteria Predicts Environment-Specific Genetic Effects on Life History Traits
Joseph D. Coolon,Kenneth L. Jones,Timothy C. Todd,Bryanua C. Carr,Michael A. Herman
click hereEvolutionary Dynamics of Regulatory Changes Underlying Gene Expression Divergence among Saccharomyces Species
Brian P.H. Metzger, Patricia J. Wittkopp, and Joseph. D. Coolon
click hereEvolution of splicing regulatory networks in Drosophila
C. Joel McManus, Joseph D. Coolon, Jodi Eipper-Mains, Patricia J. Wittkopp and Brenton R. Graveley
click hereMotivated students are encouraged to contact Dr. Coolon by email. Please include your resume, transcripts and research interests.
Those interested in pursuing graduate studies are also encouraged to contact Dr. Coolon by email. Please include your CV and research interests. Students interested in both MA and Ph.D programs are welcome. Admission is through the Department of Biology, follow this link for more information.
Openings depend upon funding and size of the lab, but students who are interested in the lab should contact Dr. Coolon directly through email and please include your CV and research interests.
Hall-Atwater Laboratories, 123
jcoolon@wesleyan.edu