Summary of Job Purpose and Principal Duties:

The School of Life Sciences at the University of Dundee is a world-class academic institution with a reputation for the excellence of its research, its high quality teaching and student experience, and the strong impact of its activities outside academia. With 900 staff from over 40 countries worldwide the School provides a dynamic, multi-national, collegiate and diverse environment with state-of-the-art laboratory, technology and teaching facilities.

We are recruiting for an exceptional individual to join us as a Postdoctoral Research Assistant within the MRC PPU.

Project: Dissecting the molecular roles of FAM83 proteins in regulating Ser/Thr protein kinase CK1 function in cells

Considered constitutively active kinases, the CK1 isoforms play critical roles in many cellular processes, including Wnt signalling, mitosis and circadian rhythms, during development and in adult tissues and are often aberrant in human disease. The Sapkota lab has uncovered the eight members of the FAM83 family as key regulators of the subcellular distribution of specific CK1 isoforms (Fulcher et al, 2018; PMID-29789297). Thus far we have shown that FAM83G/PAWS1 mediates Wnt signalling through association with CK1a (Bozatzi et al, 2018; PMID-29514862), and PAWS1 mutations (A34E; R52P) that abolish interaction with CK1 underlie the pathogenesis of palmoplantar keratoderma (Wu et al, 2019; PMID-31656861). Similarly, FAM83F, through farnesylation, delivers CK1α to the plasma membrane and mediates canonical WNT signalling (Dunbar et al, 2021; PMID-33361109). Lenalidomide and other thalidomide derivatives that are known to target the degradation of CK1α appear to also induce the degradation of FAM83F via an interaction with CK1α resulting in the inhibition of Wnt signalling. However, other FAM83-CK1α complexes are spared degradation by IMiDs (Dunbar et al, 2021; PMID-33361334). We have also shown that FAM83D regulates mitotic spindle orientation through association with CK1α (Fulcher et al, 2019; PMID-31338967). Now, we are seeking a postdoctoral fellow to establish the underlying molecular mechanisms by which FAM83 proteins control the diverse CK1 functions and define its substrates in unique signalling contexts, with a view to unearthing selective intervention strategies against specific FAM83-CK1 complexes. The successful candidate will exploit state-of-the-art cellular, molecular and proteomic tools.

Your priorities will include:

• Identify and establish CK1 substrates directed by specific FAM83 proteins in cells, by focussing on Wnt signalling (FAM83F and G) and mitosis (FAM83D) to begin with.
• Define rules and molecular mechanisms that govern the regulation of pleiotropic CK1 isoforms in distinct biological processes.
• Develop tools and reagents that allow targeting of specific FAM83-CK1 complexes in cells

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 biochemistry, cell and molecular biology, and signal transduction.
• Strong background in protein chemistry and dissecting protein phosphorylation is desirable.
• Capable of working in a diverse team, but able to plan and work independently.
• Excellent communication skills and proficiency in English.

The position is fixed-term for 30 months. The appointment will be made on University's Grade 7 salary scale.

Appointment as a Postdoctoral Research Assistant on the Grade 7 salary scale is dependent upon you having been awarded a PhD. An appointment may be considered if you have submitted a PhD thesis. In this instance, the initial appointment will be made as a Research Assistant on the Training Grade 7 salary scale until the PhD has been awarded.

Additional Information:

For details on the Sapkota lab research, current and past lab members and publications please visit our websites:

https://www.ppu.mrc.ac.uk/research/principal-investigator/gopal-sapkota
https://sites.dundee.ac.uk/sapkota-lab/

The MRC-PPU is one of the world’s most renowned centres for research on protein phosphorylation and ubiquitylation (http://www.ppu.mrc.ac.uk) and has an exciting and collaborative research environment, equipped to the highest international standards. The major aims of the MRC-PPU are to advance understanding of the role of protein phosphorylation and ubiquitylation in cell regulation and human disease; to facilitate the development of drugs to treat diseases caused by abnormalities in phosphorylation; and to generate reagents and improve technologies. Another key remit of the MRC-PPU is to train the next generation of scientists who will advance our understanding in this crucial area of medical research. The MRC-PPU is located in a beautiful setting overlooking the estuary of the River Tay and embedded within the School of Life Sciences at the University of Dundee. This is one of the premier Life Sciences research centres in the world and was recently assessed as the top UK University for Life Sciences research in the 2014 Research Excellence Framework (REF).

We are one of the UK’s leading universities – internationally recognised for our expertise across a range of disciplines and research breakthroughs in multiple areas, including science, medicine and engineering, amongst many others. Conveniently located on the banks of River Tay, our main city-centre campus is at the heart of Dundee - an up-and-coming, friendly, compact and affordable city with a rich heritage in design and technology. Just a short walk from the V&A Museum of Design Dundee, we’re close to both the train and bus stations. We also have campuses at Ninewells Hospital and in Kirkcaldy which are easily accessible via local transport links.

For further information about this position please contact Gopal Sapkota at gsapkota@dundee.ac.uk.

As an internationally diverse institution, we welcome job applicants from all countries and nationalities. The School of Life Sciences is proud to employ staff from over 40 different nations.

The diversity of our staff and students helps to make the University of Dundee a UK university of choice for undergraduate, postgraduate and distance learning. Family friendly policies, staff networks for BME, Disabled and LGBT staff, membership of Athena SWAN, the ECU Race Equality Charter and Stonewall as well a full range of disability services, create an enjoyable and inclusive place to work.