Bioinformatics and Population Genomics Group
Alan Hodgkinson currently holds a Career Development Fellowships at KCL as part of the eMedLab Medical bioinformatics partnership (https://twitter.com/emedlab7) funded by the MRC. See also Hodgkinson Lab website
The group's broad research interests are focussed on understanding how variable gene expression and post-transcriptional processing leads to diversity in the exposure of variation in RNA sequences across individuals, and impacts upon human health and disease. Our approach to addressing such questions is multi-disciplinary, applying statistical and bioinformatics techniques, as well as genetic and population biology theory to high-throughput genomic data in order to better understand biological processes. Specifically, our current research interests focus on understanding these processes in mitochondria, where we aim to identify the genetic drivers of variation in post-transcriptional processes and assess the functional impacts of such events, with a particular focus on cancer and cardio‐metabolic phenotypes.
Mitochondria are involved in a wide range of fundamental cellular processes, from cellular energy production to thermogenesis, lipid biosynthesis and cell death. So wide ranging are their functions, that diseases associated with mitochondria manifest across almost all tissues, often affecting multiple organs simultaneously, and mutations in both the mitochondrial genome and associated nuclear genes have been linked to diseases as diverse as Deafness, Alzheimer’s Disease, Diabetes, Cancer and Myopathy.
The mitochondrial genome is often transcribed as one poly‐cistronic strand containing all genes, and after transcription various processes affect RNA and protein levels, including the modification of nucleotides and poly-adenylation of messenger RNAs. One particularly important post-transcriptional process is the formation of secondary degree structures at transfer RNAs (tRNAs) within the poly‐cistronic transcript, which then serve as recognition points for cleavage by nuclear enzymes and the release of mitochondrial gene products. It is known that post-transcriptional methylation of specific nucleotides is required for the correct folding of tRNAs, and therefore these events play a vital role in mitochondrial genome processing.
Our research will focus on using genomic and bioinformatic techniques to uncover the scale of variation in post-transcriptional modification events in mitochondria on a population level and to identify the genetic drivers of such events. Furthermore, we are interested in whether these processes vary systematically in specific disease contexts and aim to ultimately unravel the functional impact of such events on human health.
The group is headed by Alan Hodgkinson who did his PhD at the University of Sussex, with Professor Adam Eyre-Walker studying variation in the mutation rate in mammalian genomes. Following this Alan did a postdoc with Dr Philip Awadalla at Sainte Justine Hospital, University of Montreal, Canada. Whilst in Montreal, Alan worked on the population genetics of French-Canadians, as well as a large gene expression study within the CARTaGENE project.