Looking to list your PhD opportunities? Log in here.
About the Project
In the last decade the involvement of the brain Renin Angiotensin System (RAS) in neurodegenerative disease, particularly Alzheimer’s disease (AD) has come to the fore. Part of this involvement is evidence of how imbalance in RAS may give rise to and exacerbate tau pathology. Effective management of or mitigation against risk factors may be one of the most effective ways of reducing rates of AD and other dementias. One often overlooked risk factor is traumatic brain injury (TBI), which can be caused by blunt or repetitive traumas, perhaps because opportunities for its prevention may be limited, although the long-term effects might be mitigated against with timely intervention. One form of TBI that has rose to prominence in relation to several forms of profession sports is that which gives rise to chronic traumatic encephalopathy (CTE). This is a progressive degenerative disease found in people who have had a severe blow or repeated blows to the head seen in a number of professional, contact or extreme sports; certain social/entertainment-based activities; and domestic violence, where repeated concussions or other brain trauma occur. Importantly, CTE is classified as a ‘tauopathy’, which means it presents with pathology associated with tau protein that is also involved in AD and some other dementias and thus there is now a timely need to explore the extent to which RAS imbalance seen in relation to AD pathology might similarly contribute to CTE pathology and severity.
Aims & Objectives
We have the knowledge and expertise to train a student to design and execute studies to investigate the RAS imbalance in post-mortem brain tissue where we wish to undertake the first investigations of its kind in relation to the neuropathology of CTE. The investigations will be towards gathering information on the extent of RAS activation in relation to CTE Pathology to inform the potential for RAS-acting drugs as possible acutely administered drugs in the event of a TBI.
The following are examples (but not a limited list) of specific hypotheses that we wish to test:
1. To what extent does RAS activation occur in CTE and in relation to CTE neuropathology.
2. What is the extent of imbalance between destructive and protective elements of the RAS in CTE.
Methods
There are multiple potential projects possible in this topic area and where following consultation we would design a suite of methodological approaches to investigate the agreed research questions. Ordinarily most studies commence with foundation experiments (using molecular genetic, biochemical, immunohistochemical and/or histological approaches) in carefully selected post-mortem brain tissue (from one or more brain regions) from diseased and non-diseased persons. These may then be extended to include complementary studies designed and executed in other laboratory experimental systems (in vitro or cell-culture based), ex vivo (in other experimental models or more human tissue sources from patients) or in vivo in small pre-clinical trials (time and resources permitting). Projects are intentionally not prescriptive at this stage as we seek to give PhD students the opportunity to develop and design projects with us from the outset as part of their initial training and input into their projects.
References
Kehoe PG et al. Angiotensin-converting enzyme 2 is reduced in Alzheimer's disease in association with increasing amyloid-beta and tau pathology. Alzheimers Res Ther. 2016;8(1):50.
Villapol S et al. Neurorestoration after traumatic brain injury through angiotensin II receptor blockage. Brain 2015; 138(11):3299-3315.
Email Now
Why not add a message here
The information you submit to University of Bristol will only be used by them or their data partners to deal with your enquiry, according to their privacy notice. For more information on how we use and store your data, please read our privacy statement.

Search suggestions
Based on your current searches we recommend the following search filters.
Check out our other PhDs in Bristol, United Kingdom
Check out our other PhDs in United Kingdom
Start a New search with our database of over 4,000 PhDs

PhD suggestions
Based on your current search criteria we thought you might be interested in these.
Investigating the conflicting roles of the renin angiotensin system in Alzheimer’s disease
University of Bristol
Investigating changes in neuronal development and connectivity in a mouse model of muscimol-induced perinatal brain injury
Royal Veterinary College
Assessing therapeutic strategies to target the counter-regulatory renin-angiotensin system in cardiovascular disease
University of Glasgow