This role will be under the leadership of Professor Terry Rabbitts We are seeking to appoint a highly motivated Post Doctoral Training Fellow. This project is a part of the of the CR-UK-Therapeutic Catalyst Grant to develop new drugs for T cell leukaemia and for ailments with excess angiogenesis.
The project is focussed on developing chemical compounds that were derived using an intracellular antibody that binds to the T cell acute leukaemia oncogenic transcription factor, LMO2. The first generation Antibody-derived (Abd) compounds have been identified and made into Proteolysis-targeting chimaeras (PROTAC) compounds. The work of this PDTF post will be to develop protocols for successful production of soluble, recombinant LMO2 protein to facilitate structural studies with the compounds, such as X-ray soaking for crystallography and other biophysical methods of studying the protein-compound complex for structure-based drug design. New generations of compounds will be synthesised by our collaborating chemistry laboratory and the PDTF will also use cell-based assays to evaluate interaction of compounds with LMO2.
You should possess a PhD in a biology subject and have experience in working with recombinant proteins, in particular antibodies and transcription factors. You must also experience with protein engineering and as well as in biophysical methods such as X-ray crystallography. Experience with cell-based models is important.
The ICR has a workforce agreement stating that Postdoctoral Training Fellows can only be employed for up to 7 years as PDTF at the ICR, providing total postdoctoral experience (including previous employment at this level elsewhere) does not exceed 10 years.
Professor Terry Rabbitts’ research is focused on new strategies using intracellular antibodies and derivates for therapy aimed at hard-to-drug chromosomal translocation gene products. This includes intracellular antibodies for inhibiting transcription factors and protein-protein interactions. The approach has resulted in compounds that bind to the chromosomal translocation LMO2 transcription factor and effect T cell leukaemia cell growth. The aim is to develop these compounds into drugs for refractory T-cell acute leukaemia’s.
Our approach is multi-disciplinary, integrating molecular biology, cell biology, antibody design, structural biology, and chemical biology. We aim to develop these LMO2 binding compounds to pre-clinical efficacy in this next round to structure-based drug evolution. These will be the first compounds to be derived from an intracellular antibody binding site that have progressed towards phase I clinical trials. The post should lead to further work in the group to drug using intracellular antibody approach.
We encourage all applicants to access the job pack attached for more detailed information regarding this role. You may contact Prof. Terry Rabbitts for further information by emailing [email protected].
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