Research Fellows Directory
Professor Robert Gilbert
University of Oxford
Our crystallographic work in post-transcriptional control has been focused on the uridyltransferase enzyme Cid1 from S. pombe. Cid1 is a homologue of human uridyltransferases involved in specific miRNA degradation pathways and is a major candidate cancer target. We have written up the description of two Apo conformers and the Cid1-UTP complex and this has been accepted for publication. We are now turning our attention to the uridyltransferases from mammals and have cloned and expressed several different-sized constructs of the enzymes ZCCHC6 and ZCCHC11. ZCCHC11 is directly and strongly implicated in the inhibition of let7 miRNA maturation and thus for example in breast cancer.
Our work on pore formation has focused on achieving publication of papers describing the triggering of endocytosis by perforin and the structure of lysenin. We are now continuing with our work on the role of incomplete (arc-shaped) oligomers of cholesterol-dependent cytolysins in forming pores via a toroidal mechanism and on the perforin-like proteins of Pladmodium and Toxoplasma which we are expressing in the lab for structural and functional studies.
In our work on cell adhesion we have two papers under resubmission describing structures of the kindlin-1 PH domain and a SAXS, NMR and integrin tail-binding analysis of kindlin-3. Our major efforts at present are associated with continued expression of full-length and fragmentary kindlins in E. coli and insect cells and the structural characterisation – for example of a kindlin PH domain-RACK1-integrin tail complex.
We have also spent time this year seeking to demonstrate the value of a novel method of resolution assessment and filtration for cryo-EM we developed, which we term the Fourier plate correlation. This takes account of resolution anisotropy during the estimation of resolution and provides a more accurate way of filtering structures than the assumption of signal isotropy where that is unwarranted.
Interests and expertise (Subject groups)