PhD student required for a multidisciplinary and international project.
Sialic acid plays a major role in several biological processes ranging from immunity, cell adhesion, neurobiology and deficiency or overexpression of sialic acid, is the causes of many diseases including: Salla disease, mucolipidosis type I (sialidoses) and GNE myopathy (GNEM), a condition that leads to weakness and wasting of muscles in the legs and arms; and the focus of this project. Although GNEM is characterized by degeneration of muscle cells, it is also shown to have other hallmarks such as aggregation of Amyloid β and accumulation of phosphorylated tau and other misfolded proteins in muscle cells, like Alzheimer disease in the brain. Anomalous sugar metabolism is the cause of several other diseases that affect numerous organs including brain and muscles.
As such, sugars such as sialic acid are interesting targets for therapeutic intervention involving chemical biology and medicinal chemistry programs. On this project the student will synthesise sialic acid derivatives or its precursors, that will then be used to investigate possible defects in the sialic acid biosynthesis/catabolism in GNEM and evaluated as a potential therapeutic agent. This will be done via development of cell and patient-derived models representing the disease or defect. The project is in collaboration with Professor Arwyn Jones at the School of Pharmacy & Pharmaceutical sciences, a leading scientist in analysis of the interaction of biological therapeutics with cells. He will serve as second supervisor for the project. Additionally, this multidisciplinary project is in association with International collaborators and the student will have join the ProDGNE consortium (https://sites.fct.unl.pt/prodgne/pages/project-0), funded by the European Joint Program on Rare Disease (EJPRD) which includes glycobiologist with expertise in CDGs in Portugal and Germany and expert in glycomics and metabolomics in Italy There might be the opportunity to spend some time in their laboratories to gain skills in sialic acid biology and metabolism.
General outline
Generation of modified carbohydrate derivatives and physical/biological characterisation using 1D & 2D NMR spectroscopy, HPLC and LC-MS, enzyme analysis via 19F and 31P. Synthesis of fluorescent carbohydrate derivatives and their biological evaluation in rescuing the GNE defects in patient-derived cellular models. Modifications to initial structures will be performed towards evaluation of leading compounds as therapeutic candidates.
Research Environment
The Cardiff School of Pharmacy and Pharmaceutical Sciences is the number one School offering the MPharm across England and Wales, and the third highest across the whole of the UK (The Complete University Guide 2022). Research at Cardiff is working across disciplines to tackle major challenges facing society, the economy, and the environment. Cardiff School of Pharmacy and Pharmaceutical Sciences has very well-equipped laboratories with 500 MHz NMR, LC-MS and modern cell biology facilities with associated expertise in biological validation of new drugs targeting numerous diseases. This includes tissue culture, protein biochemistry and advanced fluorescence microscopy. The student will also have access to range of other technologies within Cardiff University.
Training and Development Opportunities
Training will be provided in synthetic organic chemistry with particular focus in carbohydrate chemistry, organophosphorus and organofluorine compounds -see above technologies. For biological analysis training will be provided in tissue culture, live and fixed cell fluorescence microscopy and protein biochemistry. Training will also be provided in gaining skills in data handling, presentation, and scientific writing.
Academic career skills – the student will be able to participate in teaching and demonstrating activities and scientific publishing. The student will also acquire detailed knowledge of synthetic chemistry, drug design, design of biological assays, data analysis interpretation and problem solving. The student will also have the opportunity to present his/her research in our weekly lab meetings and to the consortium monthly meetings. This leading up to presentations at international conferences.
Potential students should hold a good UK bachelor’s degree (first or upper second-class honours degree) or a MSc degree in chemistry, biochemistry or a related subject. Informal enquiries are welcome can be directed to Dr. Pertusati ([Email Address Removed]) and/or Professor Arwyn T. Jones [[Email Address Removed]]
How to Apply
Applicants should apply to the Doctor of Philosophy (Pharmacy) with a start date of January 2022, by visiting our website.
In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. In the funding section, please select 'I will be applying for a scholarship/grant' and specify that you are applying for advertised funding from Development of new therapeutic entities targeting glycosylation disorders.
- an upload of your CV
- a personal statement/covering letter
- two references
- current academic transcripts/certificates.
Applicants whose first language is not English will be required to demonstrate proficiency in the English language (IELTS 6.5 with a minimum subscore of 5.5 or equivalent).
Continue with Facebook
