UCL Queen Square Institute of Neurology


Prof. G. Bates

Prof. G. Bates

Research Summary

Professor Gillian Bates has joined the Sobell Department of Motor Neuroscience from King’s College London where she was Head of the Division of Genetics and Molecular Medicine. She has been at the forefront of Huntington’s disease research for many years and has joined UCL to Co-Direct the Huntington’s Disease Research Centre with Professor Sarah Tabrizi.

The research of the Bates lab is focussed on understanding the molecular basis of Huntington’s disease (HD) and developing therapeutic interventions. Toward this aim, we work closely with the research group of Professor Tabrizi, within the Huntington’s Disease Research Centre (www.hdresearch.ucl.ac.uk). Huntington’s disease is a devastating inherited neurodegenerative disorder that affects movement and cognition and is ultimately fatal. For more information about the Huntington’s disease multidisciplinary clinic, led by Prof. Tabrizi, please visit http://hdresearch.ucl.ac.uk/hd-clinic/ and for an overview of research into HD please visit HDBuzz (http://en.hdbuzz.net/).

The mutation that causes Huntington’s disease is the expansion of a CAG repeat in the huntingtin (HTT) gene that leads to an abnormally long polyglutamine tract in the huntingtin protein (HTT). We are particularly interested in the direct effect of the mutation on HTT expression. We have found that the presence of the mutation results in the aberrant splicing of HTT resulting in the production of a small mRNA that encodes an exon 1 HTT protein. Exon 1 HTT has been shown to be highly pathogenic in a wide range of model systems. One programme of our research is directed toward understanding the molecular basis of the aberrant splicing event and determining the extent to which exon 1 HTT contributes to disease pathogenesis. We are conducting a preclinical assessment of approaches by which the generation of this small mRNA species could be prevented.

We use genetic and pharmacological approaches to validate therapeutic targets in mouse models of Huntington’s disease and over the past 10 years, have published a number of in vivo experiments which indicate that Huntington’s disease is caused by an aggregated, and not a soluble, form of the HTT protein. We are specifically interested in targeting the early stages of HTT aggregation, however, very little is known about the structure of the seeding competent aggregates that form in vivo. We are currently working with Prof. Erich Wanker (Berlin) and Dr. Gabriele Kaminski Schierle (Cambridge) to better understand the seeding and aggregation process.