Dr Giles S.H. Yeo

1.) Understanding the physiological role of known genetic modifiers influencing food intake and body-weight. The first and most robust of the genes identified by GWAS is FTO (fat mass and obesity related transcript) and we have contributed to characterizing its enzymatic function as a demethylase, identifying and characterizing loss-of-function human mutations and determining its expression and direct role in the hypothalamus influencing food intake. Whatever the explanation for the effects of intronic polymorphism on human adiposity, studies of humans and mice carrying genetic variants that functionally perturb FTO indicate that FTO itself is an important regulator of body size and composition. Recently we have demonstrated a role for FTO in the cellular sensing of amino acids, linking levels to mTOR signalling, and determined that FTO shuttles between the nucleus and cytoplasm, and also that FTO links high-fat feeding to leptin resistance through activation of hypothalamic NFкB-related signalling pathways.

3.) Developing novel bioinformatic tools, both for the analysis of next-generation sequencing data. We have, over the past few years, developed a novel solution to the processing of next-generation sequencing data, as the handling of such enormous amounts of data currently requires bioinformaticians and the use of expensive high-performance computing (HPC) clusters (Klus et al, BMC Res Notes 2012). We have developed BarraCUDA, a novel sequence alignment software that utilizes NVIDIA graphics cards to map sequencing reads to a reference genome, thus accelerating this process by 300% as compared to a standard workstation. BarraCUDA is designed with the aim of downsizing the NGS software pipeline from complex and expensive HPC clusters down to standard desktop computers.