Marie-Jose Bijlmakers

The activity of T cells is tightly controlled to ensure that effective immune responses can be elicited, whilst pathological inflammatory disorders are prevented. Numerous signals from cell-bound and soluble ligands influence the fate of T cells, and these need to be correctly relayed along multiple signalling pathways. We are interested in understanding the players and processes involved in these complex molecular networks. In particular, my lab focuses on the regulation of protein functions by posttranslational modifications through which we aim to gain insights into basic biological processes and to elucidate novel aspects of T cell regulation. <br /><br />A longterm interest is the regulation of the tyrosine kinase Lck, a Src family member that is essential for T cell development and activation. In particular, we have investigated the palmitoylation and ubiquitination of this protein, two dynamic reversible modifications. More recently, we have begun to characterize novel ubiquitin ligases with functions in the immune system. Ubiquitination critically regulates many cellular processes by influencing substrate functions in a variety of degradation-dependent and independent ways, but the proteins that mediate this modification remain poorly characterized. We are specifically studying the functions of the ubiquitin ligase RNF125, which influences T cell activation and may additionally be involved in innate anti-viral responses. A protein related to RNF125, RNF114, was recently identified as a psoriasis susceptibility gene in a whole genome association scan. The functions of this protein, and how it contributes to psoriasis, is another major research area in the lab.<br /><br />

Regulation of T cell functions; the roles of ubiquitination