BDRC SEMINAR SERIES Professor Victor Tybulewicz The Francis Crick Institute, London UK Using mouse genetics to understand Down Syndrome 19th June, 1pm Levinsky Seminar Room, ICH Abstract Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21) and results in a large number of phenotypes, including learning difficulties, cardiac defects, distinguishing facial features and leukaemia. These are likely to result from an increased dosage of one or more of the ~310 genes present on Hsa21. We are using mouse genetics to identify the dosage sensitive genes on Hsa21 that cause these phenotypes. We have generated mouse models that show cardiac defects, learning and memory deficits and locomotor dysfunction. Genetic mapping has shown that there at least two dosage-sensitive genes contributing to the cardiac phenotype, and one contributing to the locomotor phenotype. We have also been using these models to study the underlying pathological mechanisms. Biography Victor Tybulewicz obtained his PhD at the MRC Laboratory of Molecular Biology, Cambridge, working with John Walker on ATP synthases. He then carried out postdoctoral research at the Whitehead Institute, MIT with Richard Mulligan, developing methods for gene targeting in mice. In 1991 he moved to the MRC National Institute for Medical Research, London where he runs an independent research group working in two main areas. Firstly he studies signal transduction in lymphocytes, exploring the roles of signaling molecules in B and T cell development, activation and survival. Secondly, in collaboration with Elizabeth Fisher, he is using mouse genetics to understand the pathology of Down Syndrome. Together they generated the first ever transchromosmic mouse strain, Tc1, which carries a freelysegregating copy of human chromosome 21, and shows phenotypes resembling the human condition. In addition to running his own research group, he was Head of the Division of Immune Cell Biology and Head of the Immunity Supergroup at the MRC National Institute for Medical Research. On 1st April 2015 the MRC NIMR became part of the Francis Crick Institute, and Victor Tybulewicz is now a Group Leader at this Institute. He is a Member of the European Molecular Biology Organization and a Fellow of the Academy of Medical Sciences.