Department: Clinical Science and Services
This is an exciting opportunity for a veterinary graduate to join our clinical research team working on problems of the geriatric cat. This training programme is for four years leading to a PhD and will focus on the role of oxidative stress and mitophagy in feline chronic kidney disease. Training will be provided in epidemiology, bioinformatics and molecular genetics, immunological assays and other lab-based molecular techniques.
Feline chronic kidney disease (CKD) is a heterogeneous syndrome responsible for >1 in 8 deaths of cats over 5 years of age. Mineral bone disturbance, proteinuria and low red cell mass are associated with progressive renal injury but how these are linked to molecular mechanisms driving progression remains to be determined. Evidence from other species suggests that exposure of tubular cells to albumin or repeated episodes of ischaemia leads to oxidative stress and induces a pro-inflammatory phenotype of tubular cells. Also, reactive oxygen species (ROS) generated by oxidative stress trigger mitophagy, a process which removes damaged dysfunctional mitochondria and protects cells from further oxidative damage. Dysregulation of mitophagy is thought to exacerbate ROS generation and oxidative stress perpetuating the chronic inflammatory and pro-fibrotic processes.
This PhD project will examine the hypothesis that oxidative stress and dysregulated mitophagy trigger progressive feline CKD. Archived tissue, plasma and urine samples available from cats with stable and progressive CKD are available and the successful candidate will use both retrospective and prospective study design to develop experience in metabolomic and transcriptomic techniques in order to explore and address the following questions:
- Is oxidative stress characteristic of the progressive feline CKD metabolome?
- How does the renal transcriptome differ in cats with progressive versus non-progressive CKD?
- Can urinary transcriptomics be used to identify the pathways activated within the kidney that are associated with progression and be used to monitor response to treatment?
- Is there evidence to link dysregulated mitophagy to oxidative stress in progressive CKD?
- Chakrabarti S et al., (2012) Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease. J Vet Intern Med; 26(2):275-81.
- Chakrabarti S et al., (2013) Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction. Vet Pathol.; 50(1):147-55.
- Kaushal GP et al., (2019) Molecular Interactions between Reactive Oxygen Species and Autophagy in Kidney Disease. Int. J. Mol. Sci. 2019, 20, 3791; doi:10.3390/ijms20153791
- Must meet our standard PhD entry requirements
- MRCVS or a veterinary degree registerable with MRCVS
- Excellent communication and team working skills and a strong interest in feline medicine
- Prior experience of research at undergraduate or post-graduate level is desirable
This is a four year fully funded studentship, funded by Boehringer Ingelheim. The student will receive a stipend and "Home" rate tuition fees are covered. International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees.
Please note that EU/EEA and Swiss national students may no longer be eligible to pay the “home” rate of tuition fees nor claim any financial support for their studies dependent on personal circumstances (including immigration status and residence history in the UK). To help determine whether you would be eligible for home fees please see the UKCISA's 'Who pays 'home' fees for higher education in England?' guide found here.
The studentship will commence October 2022.
How to Apply
For more information on the application process and English language requirements see please see How to Apply.
If you are interested in applying for this position, please follow the link below. Please use your personal statement to demonstrate any previous skills or experience you have that are relevant to this project.
Date for interviews tbc
Deadline: 31st August 2022
We welcome informal enquiries - these should be directed to Dr Rosanne Jepson firstname.lastname@example.org