About the Project
The project is described below and interested potential applicants are encouraged to email Prof Donald Fraser at [Email Address Removed] for further information/to arrange an informal discussion of the work.
Background-significance and originality: DKD affects 40% of diabetics, and is the commonest cause of End Stage Kidney Disease in the UK, responsible for about £1 in every £77 spent by the NHS (ref NHS choices http://bit.ly/1t55IkL). Poor understanding of the mechanisms driving DKD has hampered the development of new therapies. Macrophages (MØ) in the kidney are highly heterogeneous, and distinct renal MØ subsets are damaging or protective. Recent evidence from animal models and human DKD studies suggest that renal MØ are key to progression of DKD. However, the molecular mechanisms controlling their function remain largely unknown. Previous studies have shown that alterations in microRNAs (miR), a family of endogenous short, non-coding RNA, associate with renal fibrosis in DKD patients and that tissue MØ function can be modulated by miR-regulated processes, thereby indicating that miRs are important pathogenic modulators in DN through “fine-tuning” MØ functions.
This project will dissect the MØ phenotypes associated with the progression of type 2 DN (T2DN) at the molecular level, focusing on microRNA-mediated post-transcriptional regulation, to identify unique MØ–associated microRNA signatures, which can be used as potential novel biomarkers for early detection and prevention of DKD in patients. Training objectives: 1. Using multicolour flow-cytometric and cell sorting strategies to characterise immunophenotypes, functions and activation states of distinct renal macrophage subsets during the disease course of experimental T2DN model. 2. Adopting state-of-the-art microRNA extraction/sequencing to generate comprehensive microRNA profiles of distinct renal macrophage subsets during DKD injury, in order to decipher the microRNA-predicted targets underpinning the alterations of kidney macrophage biology in the context of T2DN. 3. Implementing systems biology approaches to explore the “macrophage-associated microRNA-signatures” within urine/renal biopsied samples from established T2DN patient cohorts as potential novel biomarkers of prognostic value.
The project makes use of cutting edge techniques developed by three leading laboratories, individually expert in microRNAs, macrophages, and glomerular diseases, and with a track record of working together highly productively. The student will thus receive training in state-of-the-art experimental methods, and the supervisory team and plan of work will ensure that they become adept at working across disciplinary boundaries of clinical-, in vivo model-, and bioinformatics-approaches. Additionally, the student will be expected to transfer the knowledge/skills acquired from one lab to the others, broadening the expertise and paving the way to longer term research collaboration. The ultimate goal is to help develop personalised medicine in the management of DKD, permitting biomarker testing and implementation of novel therapies in those likely benefit from them.
Funding: This studentship is funded through GW4BioMed MRC Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£14,553 p.a. for 2017/18, updated each year).
Additional research and training funding is available over the course of the programme. This will cover costs such as research consumables, courses, conferences and travel. Additional competitive funds are available for high-cost training/research.
The research project listed is in competition with 40 other studentship projects available across the GW4 BioMed MRC Doctoral Training Partnership. Up to 8 studentships will be awarded to the best applicants.
You will need to complete both an application to the GW4 BioMed MRC DTP for an ‘offer of funding’ and to Cardiff University for an ‘offer to study’.
Offer of Funding
Applicants should apply for funding via the centralised online application form, between 11th May and 9.30am 8th June 2017. (Click ’apply online’ below)
Offer of Study
Applicants should also submit an application for postgraduate study via the Cardiff University Online Application Service https://tinyurl.com/klqxt3s
Applicants should select Doctor of Philosophy (Medicine), with a start date of October 2017.
In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. In the funding section, please select “I will be applying for a scholarship / grant” and specify that you are applying for advertised funding from GW4 BioMed MRC DTP.
If you are applying for more than one Cardiff University project, please note this in the research proposal section.
Funding Notes
Academic criteria: Applicants must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of medical sciences.
English requirements: If English is not your first language you will need to meet the English language requirements of Cardiff University. This will be at least 6.5 in IELTS or an acceptable equivalent.
Residency: Applications are welcome from both UK and EU candidates; however, as a consequence of the EU referendum result, final award decisions will depend on the outcomes of the UK/EU negotiations.