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MRC DiMeN Doctoral Training Partnership: Discovery of novel therapeutic targets in inflammatory diseases by understanding the secret RNA code with the help of artificial intelligence


MRC DiMeN Doctoral Training Partnership

Newcastle United Kingdom Bioinformatics Cell Biology Data Analysis Genetics Immunology Molecular Biology Other

About the Project

Inflammatory diseases including cardiovascular disease and systemic autoimmune diseases are the leading cause of death and disability worldwide, even surpassing cancer death rates. Importantly the long-term consequences of COVID-19 are based on the persistent of inflammation in various tissues leading to organ failure and increased morbidity and mortality. In 2020, these diseases remain a “black box” to clinicians since we are lacking important information regarding their pathogenesis and progression. To make matters worse, currently used therapies are usually effective in 1 out of 3 or maximum half of patients and no single marker is available to predict which patient will respond to which drug. Artificial intelligence has revolutionised the way we can approach these clinical problems. 

The successful applicant of this PhD programme will have the chance to explore molecular signatures of disease prognosis and response to therapy working on our lab’s as well as available RNA-seq data from peripheral blood and other “target-tissues” (cardiac, arterial, synovial) from highly phenotyped patients. Working together with three field experts and their team members, you will be offered structured training on machine learning (Prof. Westhead) and engage with the secret RNA code (chemically modified RNA nucleotides) (Prof. Stellos, Dr. Gatsiou) that radically changes the central dogma of molecular biology.  In this way, you will be enabled to look for molecular traits underpinning complex inflammatory diseases. Accordingly, you will be supported by our resident physician scientists, molecular biologists and bioinformaticians to reveal novel insights contributing towards the better patient risk stratification as well as unravelling novel therapeutic targets.

We have recently shown that an RNA code artifact, called adenosine-to-inosine RNA editing, is a critical regulator of inflammatory gene expression shared between atherosclerosis (Nature Medicine. 2016; 22(10):1140-1150) and rheumatoid arthritis, the most common systemic autoimmune disease (J Autoimmun. 2019; 4:102329). Recent technological advances such as next-generation sequencing allowing unbiased transcriptome-wide analyses make it more and more clear that phenotypically diverse diseases may be characterized by common molecular signatures, thus, welcoming the era of molecular classification of diseases and personalized medicine. Yet, “cracking” the secret RNA code in health and disease is still at its birth and many questions remain to be answered (Circ Genom Precis Med. 2018; 11(9):e001927). During this project you will combine data from modern technologies (NGS, RNA code artifacts- sequencing) with the analytical power of methods of tomorrow, like the machine learning, have to offer (J. Clin. Oncol.37 (2019) 202–212). Together, we will look for new answers to old problems: can machine learning algorithms based on the combination of transcriptome and epitranscriptome risk stratify patients improving clinical algorithms? Can they identify patients who will benefit from specific drugs based on their molecular profile? Can they identify new targetable pathways that are shared among chronic inflammatory diseases and repurpose existing drugs for their treatment?

If you are fascinated by the magic world of artificial intelligence, bioinformatics and their emerging potential in the era of personalized medicine and if you enjoy working in an inclusive, structured, supportive, multidisciplinary and diverse environment and if you share our belief that multidisciplinary team-work is the answer to complex questions…then don’t delay, apply today!

Informal enquiries are welcome to be addressed to:  or . We would be happy to offer any piece of advice supporting you throughout application process.

Further information

Lab Website

Twitter: @K_Stellos

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 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. 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

Further information


Funding Notes

Studentships are funded by the Medical Research Council (MRC) for 3.5yrs. Funding will cover UK tuition fees and stipend only. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme. Please read additional guidance here: View Website
Studentships commence: 1st October 2021
Good luck!

References

[1] Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF, Jaé N, Rossbach O, Amrhein C, Sigala F, Boon RA, Fürtig B, Manavski Y, You X, Uchida S, Keller T, Boeckel JN, Franco-Cereceda A, Maegdefessel L, Chen W, Schwalbe H, Bindereif A, Eriksson P, Hedin U, Zeiher AM, Dimmeler S. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nat Med. 2016 Oct;22(10):1140-1150. doi: 10.1038/nm.4172.
[2] Vlachogiannis NI, Gatsiou A, Silvestris DA, Stamatelopoulos K, Tektonidou MG, Gallo A, Sfikakis PP, Stellos K. Increased adenosine-to-inosine RNA editing in rheumatoid arthritis. J Autoimmun. 2020 Jan;106:102329. doi: 10.1016/j.jaut.2019.102329.
[3] Sha C, Barrans S, Cucco F, Bentley MA, Care MA, Cummin T, Kennedy H, Thompson JS, Uddin R, Worrillow L, Chalkley R, van Hoppe M, Ahmed S, Maishman T, Caddy J, Schuh A, Mamot C, Burton C, Tooze R, Davies A, Du MQ, Johnson PWM, Westhead DR. Molecular High-Grade B-Cell Lymphoma: Defining a Poor-Risk Group That Requires Different Approaches to Therapy. J Clin Oncol. 2019 Jan 20;37(3):202-212. doi: 10.1200/JCO.18.01314.

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