In the UK alone there are currently 145,000 people diagnosed with Parkinson’s disease (PD). In an increasingly aged population, this number is rising, with on average 2 people every hour told that they have PD. There is no cure, but there are a range of treatments that, if given early enough, can control symptoms and maintain quality of life. Whilst magnetic resonance imaging is useful for PD diagnosis, it cannot predict disease progression, the severity of symptoms, or indicate those who will go on to develop PD dementia (PDD).
Thus, there is a significant need to identify novel biomarkers which predict disease onset, and more importantly predict disease severity; particularly predicting those individuals that are likely to develop PDD. The identification of biomarkers for PD onset and progression will enable the rapid deployment of effective treatment strategies and improve the ability of patients to effectively plan their lives.
Circular RNAs (circRNAs) are garnering significant attention as biomarkers, with circRNA abundance (measured using RNA sequencing, RNAseq), linked to the onset and progression of several diseases such as osteoarthritis, coronary artery disease and some cancers. CircRNAs are non-coding RNAs created during the processing of primary transcripts. There is growing evidence that some are functional, acting via a range of mechanisms including regulation of microRNA levels and binding of transcription factors. Their circularity protects them from degradation, increasing their stability relative to linear RNAs, and leads to their enrichment in eukaryotic tissues during development and ageing, particularly in the brain.
The aim of this PhD is to investigate the use of ‘circular RNA molecules’ as biomarkers of Parkinson’s disease onset and progression.
In this multidisciplinary project, the student will computationally analyse RNAseq data from 5,300 samples made available from the Michael J Fox Foundation (USA), and RNAseq data generated at the Biosciences Institute and Wellcome Centre for Mitochondrial Research (Newcastle University, UK), to characterise the circRNA landscape in a range of human samples including blood, serum, plasma and brain tissue.
CircRNA abundance will be compared to key clinical and neuropathological measures of disease severity and progression in both PD and control samples with the overall aim of identifying novel circRNA biomarkers that correlate with disease onset and progression.
During the PhD project the student will be trained in the bioinformatic analysis of RNAseq data including the identification and validation of circRNAs. In addition, the student will be trained in the statistical approaches to the analysis of large omics datasets. Based at both the Institute of Biosciences and the Wellcome Centre of Mitochondrial Research, the student will have access to cutting-edge high performance computing facilities and will benefit from close collaborations with the European Bioinformatics Institute (Cambridge, UK).
Supervisory team Web Links: https://www.ncl.ac.uk/igm/staff/profile/michaeljackson.html#background https://www.ncl.ac.uk/igm/staff/profile/gavinhudson.html#research https://www.ncl.ac.uk/igm/staff/profile/maurosantibanez-koref.html#research https://www.ebi.ac.uk/about/people/osagie-izuogu
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website: http://www.dimen.org.uk/
Alhasan AA, Izuogu OG, Al-Balool HH, Steyn JS, Evans A, Colzani M, Ghevaert C, Mountford JC, Marenah L, Elliott DJ, Santibanez-Koref M, Jackson MS. (2016) Circular RNA enrichment in platelets is a signature of transcriptome degradation. Blood 127(9):e1-e11.
Izuogu OG, Alhasan AA, Alafghani HM, Santibanez-Koref M, Elliott DJ, Jackson MS. (2019) PTESFinder: a computational method to identify post-transcriptional exon shuffling (PTES) events. BMC Bioinformatics 13 Jan 2016, 17:31