The Dynamics of Cellular Pathways (360G-Wellcome-096602_Z_11_Z)

Transposable elements (TEs) are mobile DNA elements that account for substantial proportions of the genomes of most organisms. For example, TEs make up approximately 45% of the human genome. TEs have been shown to generatemutations leading to Mendelian diseases and cancers in humans. Despite their abundance and importance, the mechanisms that regulate TE insertion in eukaryotic genomes remain largely unknown. The overall aim of this project is to investigate the interplay between chromatin structure and TE insertions in eukaryotes using the model species, Drosophila melanogaster, to address several objectives: Objective 1. Decode the chromatin features that influence promoter targeting of the Drosophila melanogaster P element during artificial mutagenesis experiments. Objective 2. Identify chromatin features associated with de novo insertion sites of naturally occurring TEs using population-resequencing data. Objective 3. Investigate the chromatin properties of TE insertions in the Drosophila melanogaster reference genome. Objective 4. Develop robust software for the identification of de novo TE insertions in next generation sequencing data. This work will lead to important insights about the basic mechanisms of TE integration that can be used to interpret patterns of TE insertion in eukaryotes and potentially to harness TEs as vestors for genetic engineering or gene therapy.