DPHIL PROJECTS AVAILABLE
Professor of Gene Regulation
The Hughes group is interested in how mammalian genes are regulated and how their deregulation is linked with human disease. The ~22 thousand genes in the mammalian genome are present in the DNA of every cell but are used in complex patterns in different cell types and organs. This system to turn genes off or on, modulating their levels of activity in different cell types is central to maintaining the complex biological system that is a multicellular organism.
What has become clear from large-scale genetic studies of human predisposition to common disease is that it is the control of the use of genes, rather than the genes themselves, that is frequently damaged. It is now known that functional elements other that genes exist in our DNA and these elements act as molecular switches which interact with the genes and control their use, however the mechanisms involved are not well understood. The Hughes group integrates both bench technologies and computational approaches to try and understand how these regulatory switches or enhancer elements work and how variations in their activity in our genomes leads to increased risk of developing common diseases, such as anemia, cancer, diabetes and autoimmune diseases.
Enhancers predominantly regulate gene expression during differentiation via transcription initiation.
Larke MSC. et al, (2021), Mol Cell, 81, 983 - 997.e7
Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers.
Bejjani F. et al, (2021), Nucleic Acids Res
Chromosome Conformation Capture with Nuclear Titrated Capture-C (NuTi Capture-C)
Downes DJ. and Hughes JR., (2021)
LanceOtron: a deep learning peak caller for ATAC-seq, ChIP-seq, and DNase-seq
Hentges LD. et al, (2021)
High-resolution targeted 3C interrogation of cis-regulatory element organization at genome-wide scale.
Downes DJ. et al, (2021), Nat Commun, 12