Signal transduction from the antigen receptors of B and T cells
My group is interested in signal transduction in B and T cells, from the antigen, chemokine and cytokine receptors, as well as integrins. Signals from these receptors play critical roles in B and T cell development, activation, migration, survival and death. We are studying these processes, using gene targeting in ES cells, protein biochemistry, imaging, RNAi screens, and structural biology. Over the last few years we have focused on the following signalling proteins: Syk, Vav1, Rac1 and Rac2. Recent work has focussed on the role of Syk in signaling from the BAFF receptor and BCR.
Mouse models of Down syndrome
Trisomy of human chromosome 21 (Hsa21) occurs in ∼1 in 750 live births, and the resulting gene dosage imbalance gives rise to Down syndrome (DS), the most common known genetic form of mental retardation. In collaboration with Prof. Elizabeth Fisher (Institute of Neurology, UCL) we are interested in identifying dosage sensitive genes on Hsa21 which, when present in three copies, cause the many different phenotypes seen in DS. We are addressing this using mouse models. We have created a novel mouse strain termed Tc1 which carries a freely segregating copy of Hsa21, and which shows defects in memory, synaptic plasticity, heart development, angiogenesis and in the craniofacial skeleton. We are now creating a large panel of mouse strains trisomic for different mouse genes orthologous to Hsa21 in order to map and identify the dosage-sensitive genes required in three copies to cause specific DS phenotypes.