Characterising the function and evolution of transcription factor binding sites in Drosophila enhancers - WCUB, ENWW

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Enhancers are basically defined as cis-regulatory elements that facilitate the transcription of genes. Due to their crucial role in transcription it is important that we characterise these elements to provide a better understanding of the mechanisms behind gene regulation. Additionally, it is thought that changes in these enhancer sequences are one of the main mechanisms underlying morphological evolution; these changes are usually point mutations and insertion/deletions, which can ultimately lead to complete turnover of transcription factor binding sites. Not only is it therefore imperative that we characterize these enhancer elements to provide information about gene regulation but also to aid our understanding of cis-regulatory evolution. Many enhancer studies have focussed on their ability to recapitulate the expression of the gene under regulation, however this approach has limitations and now with new technologies such as open chromatin sequencing (ATAC-seq) and targeted genome editing (CRISPR/Cas9) we can combine multiple methods to identify, characterise and study the evolution of these enhancer elements. This project will aim to exploit these techniques to identify and fully characterise a novel enhancer of the Hox gene Ubx in the legs of the fruit fly, Drosophila melanogaster. This project will also investigate the evolution of an enhancer of the Drosophila gap gene hunchback through CRISPR analysis and mathematical modelling with an aim to better understand the mechanisms behind cis-regulatory evolution. BBSRC Priority AreasSystems approaches to the biosciencesThis project will integrate data collection activities with computational/ mathematical modelling activities to produce a better understanding of biological systems (or sub-systems). This will involve the integration of bioinformatics data and in vivo transcriptional studies to produce a transcriptional model to infer an ancestral enhancer sequence.Data driven biologyThis project will use bioinformatics tools and computational approaches to aid in the discovery of novel enhancer elements, which will then be functionally verified in vivo. Bioinformatic and computational tools will also be used infer information on enhancer evolution.