D Phil awarded 2011
Transcriptional Regulation at LTA and LTB loci
The genes of the tumor necrosis factor (TNF) superfamily in the class III region of the MHC are tightly regulated at the transcriptional level. Whilst the regulation of TNF is relatively well characterised, much less is known about the regulation of two related genes --- lymphotoxin-alpha (LTA) and lymphotoxin-beta (LTB). My work sought to elucidate the mechanisms by which LTA and LTB are regulated at the level of gene transcription, using assays of protein-DNA interaction (including DNase I footprinting, electrophoretic mobility shift assays, and chromatin immunoprecipitation) and reporter gene assays. I also assessed the impact of DNA sequence variation on this process through the resequencing of DNA samples from European and African cohorts, and through mapping gene expression for LTA and LTB as a quantitative trait.
Prior to starting my D. Phil in 2006, I was an undergraduate at the University of Manchester, where I studied Genetics (with German). I spent my year abroad working in the laboratory of Dr. Bart Janssen at the Institute of Human Genetics in Heidelberg, where I studied genetic variation in the CNDP1 gene and its implications for both diabetic nephropathy and longevity. I also spent three months as a summer student in the Helen Rollason Research Laboratory in Chelmsford, where I worked on protein expression in breast tumour samples.
Keywords: DNase I footprinting, EMSA, ChIP, reporter gene assay
This work is sponsored by the Medical Research Council