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MRC DiMeN Doctoral Training Partnership: Determination of how killer pathogenic fungi evade human innate immune defences

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  • Full or part time
    Prof J Quinn
    Dr Simon Johnston
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

More people die from fungal infections than from malaria, tuberculosis, or ‘superbugs’ such as MRSA. Candida species are an important group of human fungal pathogens causing over 400,000 life threatening infections per year. Candida albicans is the most common cause of Candida-related deaths, and there is an emerging pathogen, Candida auris, that is also of great concern. C. auris is considered a serious global health threat as it is highly drug resistant and can spread in a hospital setting leading to outbreaks. As reported recently in the Independent, at least 20 NHS Trust hospitals have been recently hit by C. auris http://www.independent.co.uk/life-style/health-and-families/drug-resistant-killer-fungus-candida-auris-nhs-hospitals-japan-life-threatening-difficult-to-a7904451.html
It is important to understand how Candida species mount responses to stresses encountered within the human host, because such responses are intimately linked with the virulence of these human pathogens. Of great interest are the multi-faceted oxidative stress responses mounted by Candida cells to survive the reactive oxygen species (ROS) encountered following phagocytosis by innate immune cells (1). The Quinn lab have identified a number of distinct signalling pathways that are vital for oxidative stress resistance in C. albicans (1). In addition, our most recent work has revealed that, in addition to being resistant to many anti-fungal drugs, C. auris is also highly resistant to ROS (2).

In this project, which is led by Professor Jan Quinn (Newcastle University: https://www.ncl.ac.uk/camb/staff/profile/janetquinn.html#research) and Dr Simon Johnston (University of Sheffield: https://www.sheffield.ac.uk/iicd/profiles/johnston), you will build on these exciting findings to determine why C. auris is highly resistant to ROS, and to identify the key oxidative stress responses important for virulence in these important human pathogens. Using a multidisciplinary approach you will be trained in the latest technologies to genetically manipulate Candida species and apply biochemical, and molecular and cell biology, approaches to study stress pathway activation. In addition you will also be trained in infection modelling using cultured macrophage cell lines, and state-of-the-art in vivo imaging of the Candida infection process in a transparent zebrafish infection model (3). This project, by delineating the precise stress responses vital for Candida stress resistance and virulence, will provide valuable information to lead the development of new anti-fungal drugs.

The Quinn and Johnston labs provide a highly supportive and vibrant training environment, as evidenced by the great track record of our previous PhD students. If you are interested in this PhD then you can contact Prof Jan Quinn ([Email Address Removed]) for an informal chat about the project and the research and training opportunities provided.

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 benefited 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: https://goo.gl/8YfJf8
Good luck.

References

(1) Dantas A, Day A, Ikeh M, Kos I, Achan B, Quinn J. Oxidative stress responses in the human fungal pathogen, Candida albicans. Biomolecules 2015, 5(1), 142-165.

(2) Day AM, NcNiff MM, da Silva Dantas A, Gow NAR, Quinn J. Hog1 Regulates Stress Tolerance and Virulence in the Emerging Fungal Pathogen Candida auris. mSphere 2018, 3(5), e00506-18.

(3) Bojarczuk A, Miller KA, Hotham R, Lewis A, Ogryzko NV, Kamuyango AA, Frost H, Gibson RH, Stillman E, May RC, Renshaw SA & Johnston SA (2016) Cryptococcus neoformans Intracellular Proliferation and Capsule Size Determines Early Macrophage Control of Infection. Scientific Reports, 6(1), 21489.

How good is research at Newcastle University in Biological Sciences?

FTE Category A staff submitted: 30.60

Research output data provided by the Research Excellence Framework (REF)

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