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Medicinal Chemistry - ‘Prion diseases: how to develop therapies for prion diseases’

  • Full or part time
  • Application Deadline
    Monday, June 10, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

This research project will be funded through a Scholarship which will be delivered jointly by the Coleg Cymraeg Cenedlaethol and Cardiff University.

Project outline:
This project will assess an innovative method for the development of therapies for prion diseases by taking advantage of a novel technology in medicinal chemistry, ‘PROTAC’ (Proteolysis Targeting Chimera) technology. Broadly speaking, PROTAC technology takes advantage of a cell’s innate mechanism for protein degradation. The idea is a simple one: connect a small molecule that recognises the PrPC protein with another small molecule that recognises the cell’s machinery used for protein degradation. Theoretically, this would be a simple and effective way of reducing the levels of PrPC and ultimately of PrPSc, which may, in the long-term, lead to a better therapy relative to the limited options currently available.

Project background:
Prion diseases are neurodegenerative conditions which currently have no viable treatment; as a result, there is no way of preventing the deterioration that leads to inexorable death. A number of diseases observed in humans and animals are classed as prion diseases e.g. Creutzfeldt-Jakob, scrapie, kuru, bovine spongiform encephalopathy etc.

It has been shown that an infectious protein, defined as the ‘prion protein’ or PrP, is the root cause of all prion diseases. Prion diseases have a distinctly unusual mechanism of infection as the prion protein (PRNP) is present in the brains of all healthy individuals. As the mechanism of prion diseases was studied in greater detail, it became clear that normal PrP (cellular prion protein, PrPC) is an innocuous form of the protein, however, it is possible for this normal PrP to misfold, yielding a highly infectious and harmful form of the protein, PrPSc (scrapie prion protein). The PrPSc acts as a template for further misfolding of normal PrP, and as a result, leads to a number of horrific diseases.

It appears that the absence of PrPC in animals does not lead to any unusual phenotypes or worrying side effects and, most important of all, these animals are resistant to infection that are caused by PrPSc.

Project aims:
1. Design and synthesise novel PROTAC compounds through the use of computational chemistry
2. Assess the compounds in different biological experiments
3. Optimise the compounds through the combined use of biological results obtained, computational design and medicinal chemistry knowledge

The main objective of the Medicines Discovery Institute (MDI) is to translate fundamental discoveries in disease processes in order to identify novel molecule targets for new drugs.

By bringing together world-leading scientists to identify and produce new potential drugs, we offer a unique way to collaborate with the pharmaceutical industry. Our research covers modern drug discovery across the spectrum of oncology, immunology, neuroscience, central nervous system and respiratory diseases.

We are looking to build essential links between our researchers and the pharmaceutical industry to allow us to translate our research into real-life products which have the potential to improve the lives of people across the world, and to put Wales on the forefront in terms of medicinal innovation.

The MDI, located in the School of Biosciences (BIOSI), offers a dynamic and motivational environment for research and learning, and combines the most modern equipment with world-leading researchers. The MDI laboratories were fully refurbished recently, and as a result of this sizeable investment, we have the equipment and resources of the highest standard for Drug Discovery Research. We cooperate with schools, institutions and different departments within the University that means the student will have access to the best facilities possible.

It will be expected of the successful candidate undertake occasional teaching duties in the Biological Sciences Department as a condition of the scholarship.

Funding Notes

The scholarship is available for a period of 3 years to cover the cost of UK / EU fees and a maintenance grant (which can be used in the UK). £ 15,009 for 2019-20). (If you are a not a home or EU student you will have to finance the difference between home/EU and international fees)

Eligibility criteria
Welsh language requirement: Must submit thesis through medium of Welsh
Academic criteria: 2.1 Chemistry degree or 2.2 degree (Chemistry) + master's degree or additional relevant professional experience.
Applications from other relevant subjects (Pharmacy, Biochemistry etc.) will be considered

How good is research at Cardiff University in Biological Sciences?

FTE Category A staff submitted: 54.70

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

Click here to see the results for all UK universities

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