Key Information Starting Salary: Dependent on previous relevant Postdoctoral experience.
Duration of Contract: Fixed Term until 31 August 2023
Hours per week: 35 hours per week (Full Time)Closing Date: 24th July 2022
Many cancer-causing proteins, such as mutant RAS family members, are considered to be hard-to-drug and blocking protein-protein interactions with compounds is challenging. Intracellular antibodies are starting points as inhibitors to target hard-to-drug proteins and to block protein-protein interactions. In previous work, we have shown that intracellular antibodies can be used in chemical library screening to identify hit chemical matter that represents surrogates of the antibody binding site. This has resulted in pan-RAS binding compounds. We are implementing these antibody-derived compound technologies to produce Abd compounds that are KRAS-specific binding compounds.
We are seeking a highly motivated Post Doctoral Training Fellow for this project supervised by Prof. Terry Rabbitts into the characterization of chemical compounds that bind to RAS proteins, in particular KRAS, and structure-based drug design for hit to lead development of potential KRAS-binding compounds.
This project aims to perfect compounds that can ultimately be developed into drugs to target KRAS in human cancers.
You should possess a PhD in molecular or structural biology, or chemistry, and have an excellent track record in biomedical research and experience in working with recombinant proteins, in particular antibodies. You must also have an excellent track record with biophysical methods for protein interaction with chemical hits.
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 with new strategies using intracellular antibodies and derivates for therapy aimed at hard-to-drug chromosomal translocation gene products.
We are focused on with new strategies for therapy aimed at chromosomal translocation gene products, like LMO2 and translocation protein fusions, and hard-to-drug proteins, like mutant RAS and MYC. We are developing technologies using intracellular antibodies with warheads (such as E3 ligase for protein degradation or pro-caspases for induced cell death) together with methods to allow systemic delivery of these protein macromolecules (designated macrodrugs). Our work has also recently shown that the binding sites of singe domain intracellular antibodies to the target protein (the paratope-epitope interaction region) can used to select small molecule compounds that act as surrogates of the antibody for drug discovery.
The long term goal is creation of generic strategies for deploying intracellular antibodies are drugs per se and for using intracellular antibodies in small molecule drug discovery programmes. In particular, this work is aimed at allowing the many chromosomal translocation fusion proteins, found in blood cancers, in sarcomas and in carcinomas, to be used as drug targets in cancer treatment.
Our research is multi-disciplinary, integrating molecular and cellular biology, intracellular antibody design, chemical biology and structural biology.
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 firstname.lastname@example.org.
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The Institute of Cancer Research, London, is one of the world’s most influential cancer research institutes, with an outstanding record of achievement dating back more than 100 years. Further information about working at the ICR can be found here.
We look forward to receiving applications from all candidates, wherever in the world they are currently based. We will select those who display the potential to become, or to support, the world leading cancer researchers of the future based on their application and performance at interview. However, we particularly welcome British applicants from black and ethnic minority backgrounds, as they are under-represented within the ICR and nationwide in STEM roles.