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MRC DiMeN Doctoral Training Partnership: RNA modifications: cracking the RNA code in health and disease


Project Description

Inflammation comprises a fundamental biological process tasked to protect our body against invasion of microorganisms (e.g virus, bacteria, etc). Although acute inflammation is usually beneficial for the organism to repair tissue damage, the maintenance of inflammation for a long time, a condition called chronic inflammation, induces tissue injury and is linked to several human diseases. For example, atherosclerotic heart disease, the number one cause of death in the western world, is characterized by a chronic inflammatory state leading to the narrowing or blocking of blood vessels and thus utterly to heart attack, stroke, dementia and ultimately death. Similarly, autoimmune disorders, when our body’s natural defense system attacks its own healthy tissues, may impact significantly and perhaps irreversibly our quality of life. Unfortunately, in 2019, these diseases remain yet incurable and to make matters worse they are well-interconnected to each other. But, is there a common molecular link among them?

According to the central dogma of molecular biology our genetic code (DNA) is copied to a messenger RNA, which may ultimately serve as a template for the assembly of our proteins. RNA has been traditionally thought to be composed of 4 canonical (A, U, C, G) nucleotides. However recent technological advances revealed more than 140 chemical modifications of the 4 canonical nucleotides highlighting the structural and functional repertoire of RNA. We have previously shown that RNA editing is a critical regulator of gene expression in atherosclerosis (Nature Medicine. 2016; 22(10):1140-1150) and in autoimmune disease (J Autoimmun. 2019; 4:102329). Yet, cracking the RNA code in health and disease is still at its birth (Circ Genom Precis Med. 2018; 11(9):e001927).

The successful applicant of this PhD program will be eager to be trained in a wide spectrum of cutting-edge technologies covering a range from molecular biology and genetics from a single nucleotide resolution up to the whole transcriptome level. Our multidisciplinary award-winning lab (www.StellosLab.com) will offer you the unique opportunity to evolve your analytical and communication skills and to explore novel and pioneering concepts that will prepare you for a competitive career in academia and industry of tomorrow. Building upon the bioinformatics expertise of our lab and network, you will learn how to develop machine learning pipelines looking for patterns in the “epitranscriptome” (RNA modifications) in order to find new answers to old problems: do RNA modifications control gene expression and immune responses? Can RNA modifications predict the course of inflammatory diseases including atherosclerotic heart disease or autoimmune diseases? Can RNA modifications predict drug response? Can we therapeutically target the RNA modifications in the benefit of our patients? Depending on your interests and background, the project will be tailored accordingly (oriented either on molecular and cell biology or on bioinformatics).

Last but not least, you will be studying at the world-leading research-intensive Newcastle University in the UK, and you will be fully supported to participate in world-class “elite” scientific meetings and visit collaborative laboratories around the globe.

So, don’t delay…apply today!


Supervisor details:

Main Supervisor: Prof. Konstantinos Stellos
University webpage https://www.ncl.ac.uk/cardio/staff/profile/konstantinosstellos.html
Lab website http://www.StellosLab.com
Twitter @K_Stellos

Co-Supervisors: Prof. Ioakim Spyridopoulos, Dr. Aikaterini Gatsiou and Dr. Simon Tual-Chalot

Please do not hesitate to get in touch to discuss the project in more detail or to find out more about us and our lab at


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/

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs.
Includes:
- Stipend at national UKRI standard rate
- Tuition fees
- Research training and support grant (RTSG)
- Travel allowance

Studentships commence: 1st October 2020.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: View Website

Good luck!

References

Increased adenosine-to-inosine RNA editing in rheumatoid arthritis. J Autoimmun. 2019; 4:102329.

Dawn of Epitranscriptomic Medicine. Circ Genom Precis Med. 2018; 11(9):e001927.

Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nat Med. 2016; 22(10):1140-1150

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