卡迪夫大学招收生物物理博士
About the Project
This is an exciting PhD opportunity to develop biophysical and protein crystallography approaches to enable new drug discovery projects for rare neurological diseases. The student will be based at the Medicines Discovery Institute at Cardiff University which is a world-leading centre of drug discovery and development for diseases of the brain, fully integrated with clinicians and patients.
This scholarship, which is funded by the Coleg Cymraeg Cenedlaethol and the Medicines Discovery Institute at Cardiff University will focus initially on enabling a drug discovery project for Krabbe disease. Krabbe disease is a rare, genetic, lysosomal storage disorder that occurs at a frequency of about 1 in 100,000 live births. Patients appear healthy for the first few months, but then present with irritability, rigidity, unexplained fever and seizures usually before 6 months of age. Disease progression is rapid, with a stalling in developmental progression, and death typically occurs at 2-4 years of age.
We have developed a robust hypothesis that by inhibiting an enzyme known as acid ceramidase we can correct the accumulation of toxic materials within the lysosome and thus by doing so provide a potential therapy for children affected by Krabbe disease.
Project background
Designing novel inhibitors of the enzyme acid ceramidase
In the quest to discover a treatment for Krabbe disease, we are bringing together the expertise of Prof Simon Ward (drug discovery and drug design), Dr Helen Waller-Evans (lysosomal biology and disease knowledge) and Dr Ben Bax (biophysics and crystallography). This team supports a wider group of other scientists and students working to discovery novel therapies for patients suffering from lysosomal storage disorders.
Integral to this quest is to significantly improve our understanding of how molecules can interact with and inhibit the enzyme. This would allow us to design improved molecules which would have the potential to be novel drugs.
Methodologies required
Biophysical assays
Within the Medicines Discovery Institute we have established a biophysical laboratory equipped with a state-of-the-art Creoptix WAVE machine which can measure real-time biological interactions with exceptionally high sensitivity and resolution. This technique is industry-standard for assessing and evaluating the interaction of a small molecule (such as a potential drug molecule) and a protein.
X-ray crystallography
The gold-standard method for confirming the site and mechanism of action of drug molecules is X-ray crystallography. Dr Ben Bax is a world leading expert in protein crystallography techniques and will support the student in modern techniques including single crystal X-ray diffraction; electron diffraction; plasma focussed ion beam milling; fragment screening; protein production and purification; data collection and processing.
Environment
The main objective of the Medicines Discovery Institute 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 offers a dynamic and motivational environment for research and learning, and combines the most modern equipment with world-leading researchers. The MDI’s laboratories were recently refurbished, and as a result of this sizeable investment, we have the best possible facilities at our disposal for Medicines 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.
Studentship information:
The studentship will commence in October 2023 and will cover your tuition fees (at UK level) as well as a maintenance grant. In 2022-2023 the maintenance grant for full-time students was £17,668 per annum. As well as tuition fees and a maintenance grant, all School of Biosciences students receive access to courses offered by the University’s Doctoral Academy and become members of the University Doctoral Academy
As only one studentship is available and a very high standard of applications is typically received, the successful applicant is likely to have a very good first degree (a First or Upper Second class BSc Honours or equivalent) and/or be distinguished by having relevant research experience.
How to apply:
You can apply online - consideration is automatic on applying for a PhD in Biosciences, with an October 2023 start date.
Please use our online application service at
https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/biosciences-phd-mphil-md
and specify in the funding section state the name of the funder/that you wish to be considered for Coleg Cymraeg Cenedlaethol (CCC) & Medicines Discovery Institute (MDI) funding.
Please specify that you are applying for this particular project and the supervisor.
Information on the application process can be found here
http://www.cardiff.ac.uk/study/postgraduate/applying
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