Postdoctoral Research Assistant

Division of Signal Transduction Unit (DSTT):

The Division of Signal Transduction Therapy (DSTT) was established in 1998. This division operates as a unique collaboration between scientists in the MRC PPU and signalling researchers at the University of Dundee’s School of Life Sciences (Simon Arthur, Doreen Cantrell, Aless io Ciulli, Ron Hay, Angus Lamond, Henry McSorley, Ignacio Moraga, Adrian Saurin) and three leading pharmaceutical companies (Boehringer Ingelheim, GlaxoSmithKline, Merck Serono). The DSTT is widely regarded as a model for how academia should interact with industry. The DSTT operates as a simple bridging mechanism to enable our PIs working on ubiquitylation and phosphorylation to effectively interact with three major pharm aceutical companies to help accelerate the early stages of drug discovery.

We are looking for an exceptional individual to join the Sapkota Lab as a Postdoctoral Research Assistant to investigate the molecular roles of the FAM83 family of proteins. We have found that FAM83 proteins are the master regulators of CK1 kinases, which themselves are critical for normal cell function and are dysregulated in many diseases, including cancer (PMID: 29789297). We have established that specific FAM83-CK1 interactions are key in controlling a variety of cellular processes ranging from WNT signalling (PMID: 29514862; 33361109; 33361334) to cell division (PMID: 31338967) and can play direct roles in disease pathology (PMID: 31656861).

Given the importance of FAM83-CK1 interactions, it is critical that we now understand the molecular basis of these and determine how specific FAM83 proteins deliver CK1 activity to specific substrates to control CK1 biology. We will employ cutting edge technologies, such as CRISPR/Cas9 genome editing, Cryo-EM & crystallography, mass- spectrometry, and organoid models, in this endeavour. Furthermore, the project aims to use PROTACs and molecular glue degraders to target the degradation of specific FAM83-CK1 complexes as an innovative strategy to inhibit cancer cell proliferation.

Your priorities will include:

• Undertaking research aimed at understanding the molecular basis of FAM83-CK1 interaction by employing structural approaches and developing cell models to dissect the impact of disrupting specific FAM83-CK1 interaction on cell signalling and proliferation, with a particular focus on WNT signalling.
• Project development and implementation, including experimental design and development of cell lines using CRISPR/Cas9 genome editing. Develop tools and workflows to dissect WNT signalling pathway and consequences of targeted degradation of specific FAM83-CK1 complexes.
• Performing protein purifications for structural studies and biophysical measurements of protein-protein interactions.
• Working closely and collaboratively with a team of postdoctoral fellow and PhD students working on different FAM83 proteins.
• Discussing scientific work at internal meetings, meetings with DSTT industrial partners and at conferences.

Who we’re looking for:

• PhD with an outstanding track record and at least one first-authored publication in an internationally recognised peer-reviewed journal.
• Strong background in cell and molecular biology, biochemistry, and signal transduction, with expertise in protein chemistry and reversible protein phosphorylation desirable.
• Strong background in protein expression and structural biology is desirable.
• Strong background in WNT signalling and cancer biology is desirable.
• Capable of working in a diverse team, but able to plan and work independently.
• Excellent communication skills and proficiency in English.

For further information about this position please contact:

Gopal Sapkota at g.sapkota@dundee.ac.uk.

To find out more about MRC PPU please visit: https://www.ppu.mrc.ac.uk/

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