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MRC DiMeN Doctoral Training Partnership: Characterising a novel innate immune signalling pathway in tumour-associated macrophages by proteomics


Project Description

Applications are invited for a 3.5-year MRC DTP PhD studentship to work in the group of Prof Matthias Trost at Newcastle University on a collaborative project with Prof Claire Lewis at the University of Sheffield.
The immune system and particularly tumour-associated macrophages have become the main target for anti-cancer therapy (Yang et al, Cancer Res, 2018; Lapenna et al, Nature Rev Immunol, 2018). This exciting project will use cutting-edge proteomics to characterise a novel innate immune signalling pathway in macrophages and characterise its role in cancer. This may open up new avenues for cancer treatment.

Proteomics is a remarkably sensitive method to identify and quantify large numbers of proteins in biological samples such as stem cells, cancer or immune cells and has revolutionised biology by allowing global analysis of cellular events. Our lab has in recent years successfully developed novel proteomics methods and applied them in various areas of including macrophage biology (Hartlova et al, EMBO J, 2018; Miettinen et al, EMBO J, 2018; Trunk et al, Nature Microbiology, 2018). In this project you will learn and apply this exciting technology to understand the roles of a specific signalling pathway in macrophages and their role in cancer. In addition you will have the opportunity to learn many other molecular biology, cell biology and biochemistry techniques such as generation of Crispr Cas9 knock-out cell lines, immunofluorescence microscopy and flow cytometry.

Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in biochemistry, chemistry, biology, immunology or a related field. In addition, the candidate should be motivated, able to work independently and thrive in a multi-disciplinary and international research environment. Good communication skills are essential as is the ability to work as part of a team.

The Institute for Cell and Molecular Biosciences (ICaMB) at Newcastle University is funded and equipped to the highest international standards. Our new mass spectrometry facility is equipped with state-of-the art-mass spectrometers including an Orbitrap Fusion Lumos.

In addition to an excellent scientific environment Newcastle offers an exciting city, has a very affordable cost of living compared to places in the south of the UK and countryside of outstanding beauty. Information on moving and establishing yourself in Newcastle as a PhD student is available from the ICaMB postgraduate society PANIC https://www.ncl.ac.uk/camb/postgraduate/panic/ . More information can be obtained on the web pages of both labs (https://trostlab.org/ and https://www.sheffield.ac.uk/oncology-metabolism/staff/lewis ) or by contacting Prof Matthias Trost by email:

Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond.
See how our current DiMeN students have benefitted from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs
Includes:
Stipend at national UKRI standard rate
Tuition fees
Research training and support grant (RTSG)
Travel allowance
Studentships commence: 1st October 2019.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: View Website
Good luck.

References

Three relevant publications:

1. Yang, M., McKay, D., Pollard, J. W. & Lewis, C. E. Diverse Functions of Macrophages in Different Tumor Microenvironments. Cancer Res. 78, 5492-5503, doi:10.1158/0008-5472.CAN-18-1367 (2018).

2. Hartlova, A., Herbst, S., Peltier, J., Rodgers, A., Bilkei-Gorzo, O., Fearns, A., Dill, B. D., Lee, H., Flynn, R., Cowley, S. A., Davies, P., Lewis, P. A., Ganley, I. G., Martinez, J., Alessi, D. R., Reith, A. D., Trost, M. & Gutierrez, M. G. LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages. EMBO J. 37, doi:10.15252/embj.201798694 (2018).

3. Guo, M., Härtlova, A., Gierliński, M., Prescott, A.R., Castellvi, J., Hernandez Losa, J., Dill, B.D., Emmerich, C., Ritorto, M.S., Barton, G.J., Russell, D.G., Ramon Y Cajal, S. and Trost, M. Triggering MSR1 promotes JNK-mediated inflammation in IL-4 activated macrophages, bioRxiv 382853; doi: https://doi.org/10.1101/382853

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