The challenge in genomics is to identify DNA changes that predispose individuals to common disease; the challenge in genetics is to determine how these changes alter gene expression programmes; and, the challenge in cell biology is to find out how these altered programmes affect development, cells and organs. Our research uses cutting-edge technologies and analytical approaches in genomics, transcriptomics, and cell biology to trace the causal links from DNA change to physiological outcome. This research is thus positioned at the intersection between disease genomics, computational biology and experimental determination of molecular mechanism.
We are currently pursuing three research projects:
lncRNAs. We have been funded by a Wellcome Trust Investigator Award to investigate the molecular mechanisms of long noncoding RNAs (lncRNAs) in modulating mitochondrial function. More specifically, we use computational and experimental approaches to study many lncRNAs which, through their direct binding to microRNAs, modulate the abundance of transcripts encoding key mitochondrial proteins. We have shown that by altering the levels of these transcripts we can change catalytic rates in the oxidative phosphorylation pathway.
Disease genomics. We use functional genomics approaches at the human population level to explore the causal chain linking DNA sequence variation with altered transcription factor binding, and thereon with changes in gene expression levels. Our intent is to use newly developed technological and analytical approaches to add one last link in the chain, namely how genetic control of expression contributes to complex disease susceptibility. This research is funded as part of MRC Core funding.
Single cell genomics. Together with Thierry Voet of the Sanger-EBI Single Cell Genomics Centre, of which Ponting is a founding member, we are developing new analytical and experimental approaches for understanding the biology of single cells. One application of this technology is the transcriptomic analysis of single thymic epithelial cells (Wellcome Trust Strategic Award jointly held with Prof Georg Hollander, Oxford). The ability to sequence, using G&T-Seq, both the DNA and RNA from the same single cell now allows genotype-phenotype relations to be inferred for each cell from among a heterogeneous mixture of cells. This will be most useful when tracing the transcriptional consequences of mutations introduced across cancer cell lineages.
The group also contains substantial expertise in the prediction of molecular function and structure from the identification of very divergent homologues, and is interested in enhancing training capacity and capability in the UK and Europe.