Ongoing research in the Coolon lab falls into three primary areas:
Ecological and Evolutionary Genomics
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.
Genetics of Host Specialization in Drosophila
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.
Information Flow Through Regulatory Networks
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.