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EASTBIO: Inhibitors of gene expression to treat parasitic nematode infections


   School of Medicine, Medical Sciences & Nutrition

  ,  Thursday, December 16, 2021  Competition Funded PhD Project (Students Worldwide)

Aberdeen United Kingdom Biochemistry Bioinformatics Genetics Molecular Biology Veterinary Sciences Parasitology Pharmacology

About the Project

Supervisors:

Dr Berndt Müller - University of Aberdeen, Institute of Medical Sciences -

Professor Jonathan Pettitt - University of Aberdeen, Institute of Medical Sciences -

Parasitic nematode infections have global human health, welfare, and economic impacts; they have direct effects on the health of their human hosts and through infections of livestock and crop plants, they jeopardise food security and compromise economic sustainability. There is a limited pool of drugs to treat animal and human parasitic nematodes and resistance to existing therapeutics is a growing challenge. Control of plant parasitic nematodes is frequently reliant upon harsh, environmentally damaging soil treatments. There is thus a pressing need to develop new, broad-specificity drug treatments. 

Nematodes use an unusual gene expression strategy, spliced leader trans-splicing, which is absent from their vertebrate and plant hosts, making it an ideal source of drug development targets. Spliced leader trans-splicing is dependent on a set of essential, highly conserved, nematode-specific proteins and non-coding RNAs and research in the Aberdeen Worm Lab (https://www.aberdeenwormlab.org/) is directed towards understanding the molecular machinery that directs nematode spliced leader trans-splicing, using the many experimental advantages of the model nematode C. elegans.

This project is focused on exploiting our recent work to develop high-throughput assays that can be used to identify or engineer novel compounds as inhibitors of the spliced leader trans-splicing machinery. Such compounds can thus be developed into drugs that impair the viability and reproductive capacity of parasitic nematodes. The research will be conducted in collaboration with BioAscent Discovery Ltd. (Newhouse, Scotland), who have extensive experience of drug discovery, ranging from in vitro assay development through to identification and development of clinical therapeutic candidates.

The project would suit a student who wants to gain experience of drug discovery and development strategies, in both an academic and commercial setting. It involves applying the knowledge gained from basic biochemistry and molecular genetics to the discovery and development of novel, small-molecule inhibitors, as well as exploring the use of recently developed novel strategies such as RIBOTACs (Ribonuclease Targeting Chimeras) and PROTACs (Proteolysis Targeting Chimeras) to inhibit spliced leader trans-splicing (see https://doi.org/10.1016/j.chembiol.2019.07.015 for a brief introduction of these two approaches).

You are strongly encouraged to direct any questions about this project to Berndt Muller () or Jonathan Pettitt ().

Application Procedure:

Please visit this page for full application information: http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts to Alison Innes at

Two references should be provided by the deadline using the EASTBIO reference form.

Please advise your referees to return the reference form to

Unfortunately due to workload constraints, we cannot consider incomplete applications


Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.
This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition (limited funding is available to provide international tuition fees). Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
Candidates should have (or expect to achieve) a minimum of a 2:1 UK Honours degree, or the equivalent qualifications gained outside the UK, in a relevant subject.

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