About the Project
Oculopharyngeal muscular dystrophy (OPMD) is a degenerative neuromuscular disorder with the onset of symptoms usually occuring between the ages of 40 and 50, resulting in reduced life expectancy and severely reduced quality of life. OPMD is classified as a rare disease, however, recent studies have suggested that the low rate of prevalence, variable presentation of symptoms and lack of objective biomarkers leads to the condition being both misdiagnosed and underdiagnosed in the general population. The lack of objective biomarkers for diagnosis as well as for monitoring the progression of disease and efficacy of treatment make clinical management of OPMD challenging which makes identifying new biomarkers a crucial goal to help improve patient outcomes.
The metabolome is the complete set of small molecule metabolites present within a biological sample, and in essence represents the ultimate consequence of interactions of the genome with the environment, making it very sensitive to physiological and pathological changes, and as such, it is an ideal molecular pool to explore for biomarkers. In this project the student will use liquid chromatography – mass spectrometry (LC-MS) based metabolomics to identify objective biomarkers of OPMD pathology, progression and treatment to facilitate improved clinical management of the disease. This work will build on previous data generated by this group and collaborators that has demonstrated that OPMD has a significant impact on metabolism and that treatment with an anti-myostatin antibody partially reverses these metabolic shifts as well as helping to reverse muscle wasting.
AIMS AND OBJECTIVES
The project aims to identify highly specific blood based biomarkers of OPMD disease pathology, progression and treatment to improve clinical diagnosis and decision making as well as providing more sensitive outcome measures for drug development and clinical trials. The work in this project will be split into two broad objectives:
1) Identify blood-based biomarkers of OPMD pathology to help improve accuracy of diagnosis to reduce miss-diagnosis and under-diagnosis of the disease.
2) Identify objective markers of OPMD progression that change over time and that not only correlate to the progression of disease but are also reversible with effective treatment.
TRAINING TO BE PROVIDED:
· Analytical biochemistry – including assay development with a view to optimising key analytical parameters such as sensitivity, accuracy, precision and reproducibility.
· Liquid chromatography – mass spectrometry (LC-MS) – including developing and optimising new methods from scratch.
· Bioinformatics – including processing and handling mass spectrometry data, from raw MS data outputs through design and execution automated data processing pipelines.
· Biomarker discovery and validation –the student will be trained in assessment and validation of clinical markers, including development of targeted MS assays as appropriate.
· Biostatistics – including use of multivariate discriminant analysis’s, and machine learning approaches.
Applicants must have a 2.1 bachelor’s degree in biochemistry or molecular biology. A master’s degree in biochemistry, molecular biology or a related subject would be advantageous. The candidate should have experience of practical laboratory work as well as having successfully completed a research project. Experience of mass spectrometry, bioinformatics or quantitation of biomolecules in patient samples would be an advantage, although full training in all required methods will be provided.
English language requirements for Postgraduate Research degrees: IELTS 6.5 overall, writing 7.0, no other subscores lower than 5.5.
Please refer to the following link on how to apply: https://www.royalholloway.ac.uk/studying-here/applying/postgraduate/how-to-apply/
When applying and in all correspondence, specify the project Title, project code (BiolSci2021-Snowden) and mention this Find-a-PhD advert. Shortlisted candidates will be contacted by the end of May. Interviews will be held online in the first week of June or shortly thereafter. Project supervisors welcome informal project enquiries via email.
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