Because of the involvement of metal in numerous biological processes, in particular in oxidative stress and enzymatic action, the study of metal chelators as potential therapeutic agents has been growing. Metal chelators are being studied as mediators of oxidative stress and metal dyshomeostasis in neurodegenerative diseases such as Parkinson’s Disease, for example clioquinol and deferiprone. Metal chelators that can inhibit the action of metalloenzymes involved carcinogenesis in have also potential to stop growth of cancerous cells.
The project will synthesise novel metal chelators of the hydroxypyridinone family that have been designed specifically as neuroprotective agents or as cancer-targeting compounds. Hydroxypyridinone have been chosen for their strong and selective binding of trivalent metals such as Fe(III). These thermodynamic properties should give a good dose-effective inhibition of enzymes (cancerous cell lines) and/or inhibition of Fenton reaction (oxidative stress in neurodegenerative diseases). Numerous literature report suggest this class of compounds have a strong potential and work in our laboratory support this opinion. We have now designed more advanced derivatives of this class to optimise their biological functions.
The project will also screen these compounds for preliminary biological action, under the supervision of our collaborators. The student will perform initial tests to assess the ability of the compounds to rescue neurons subjected to toxins that trigger Parkinsonism and will on cancerous cells to assess the ability of the molecules to kill them in preference to healthy cells. Other standard biological assay will also be performed to try and identify the mechanism of action of these molecules.
The candidate must have strong undergraduate experience in organic synthesis with ideally a strong background in inorganic and physical chemistry. The candidate will be trained to screen their synthesised compounds on cells lines for assessing their biological activity. An understanding of medicinal chemistry and biochemistry would be an advantage.
Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.
For further details of how to apply, entry requirements and the application form, see https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/
Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed. Applications that do not include the advert reference (e.g. SF18/…) will not be considered.
Deadline for applications: 1st July 2019 for October 2019 start, or 1st December 2018 for March 2019 start
Start Date: October or March
Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality and is a member of the Euraxess network, which delivers information and support to professional researchers