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Decoding the RNA code of host immunity: implications for human disease


Biosciences Institute

Prof K Stellos , Dr A Kanhere , Prof S A Przyborski , Dr A Gatsiou Friday, January 22, 2021 Competition Funded PhD Project (Students Worldwide)
Newcastle United Kingdom Biochemistry

About the Project

A derailed innate immunity underpins the pathogenesis of many diseases including autoimmune disease, cancer, cardiovascular disease, and aging. Our cells are equipped with specialized tracking systems that prevents them from being in a constant state of alert due to an aberrant activation of our immune system. These tracking systems have been developed to sense perfectly matched long double-stranded RNAs (long-dsRNAs) which are immediately recognized as intruders because they are usually indicative of a virus presence, and therefore they trigger this persistent immune response. If these surveillance systems do not work properly, our cells will suffer from an inflammatory overload and eventually will be compromised. A modification on adenosine (A) RNA nucleotides that converts A into inosine (A-to-I RNA editing) on these long-dsRNAs has been shown to be the key for this fundamental biological process. We found that Adenosine deaminase acting on RNA-1 (ADAR1), which catalyses A-to-I RNA editing, is highly expressed in endothelial cells which line the inner layer of our blood vessels spanning our body. Importantly, we found that ADAR1 prefers indeed to edit those long-dsRNAs in endothelial cells with functional consequences like development of inflammatory diseases. We now want to know what happens next and how exactly ADAR1-RNA editing does that?

To address this question, we will employ a variety of traditional but also more advanced and innovative RNA and cellular biology technologies of tomorrow such as epitranscriptomics, stem cells and genome editing approaches to study this RNA modification, that pioneered the emerging field of epitranscriptome. The student will also be trained in 3D cell culture models which represent an excellent alternative to minimize the use of small animal experimentation without compromising the physiological significance of their findings.

The prospective candidate will get advantage of the large collaborative network and gain additional soft skills, like presentation and writing skills, as they will be encouraged to participate in scientific meetings. The methodological portfolio of this project may be challenging but guarantees a competitive career. In this endeavour, you will not be alone but you will be trained and supported all the way by a multidisciplinary and structured environment of both early and senior researchers in two world-leading universities in the UK. 

Informal enquiries may be made to

HOW TO APPLY

Applications should be made by emailing with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Application Details Form (Word document) to , noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. 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.
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