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Investigating a parasite-specific gene expression mechanism for the identification of novel anthelmintic drug targets


Project Description

Nematode parasites remain a major cause of neglected human disease and make significant global impacts on the health of agriculturally important animals and plants. Resistance against the limited pool of drugs (anthelmintics) available to treat these infections is on the rise, creating a demand for new, preferably wide-range interventions to combat parasitic nematodes.

We aim to identify new drug targets among the proteins and RNA molecules that are involved in an essential nematode gene expression process. Spliced leader trans-splicing is a conserved and essential step involved in the maturation of most mRNAs and is dependent on a set of nematode-specific factors whose functions and biochemical activities are poorly understood. As this process is conserved in all known nematodes, we are exploiting the manifold advantages of C. elegans as an experimental system. Through this approach we will gain the insight needed to develop nematode spliced leader trans-splicing mechanisms as novel drug targets.

Known spliced leader trans-splicing factors will be epitope tagged using CRISPR genome engineering, so they can be immunoprecipitated, allowing the identification of protein and RNA interaction partners by mass spectrometry and RNA-Seq, respectively. The function of these new factors will then be further explored using a variety of approaches including gene knock-down by RNA interference to identify defects in spliced leader trans-splicing, in vivo localisation studies and protein-protein and protein-RNA interaction assays. The combination of these approaches will lead to the identification of new factors required for spliced leader trans-splicing, together with a more complete understanding of the roles of known components.

The immediate outcome of this work is a better understanding of the mechanism underlying an essential parasite-specific gene expression strategy. Ultimately, the knowledge gained will inform approaches for the development of new anthelmintics.

The project will provide training in widely-used, transferable techniques, including CRISPR genome engineering, animal genetics, reverse-transcription qPCR, molecular cloning, fluorescent microscopy, RNA interference, immunoprecipitation, RNA-Seq and mass spectrometry (LC-MS/MS)- based proteomics.

We are looking for candidates with a background in Molecular Biology, Cell and Developmental Biology, Microbiology, Molecular Parasitology, or a related area, who are enthusiastic about investigating fundamental biological processes that have significant potential for novel drug development.

You can find further information about us, the lab and our research on https://www.aberdeenwormlab.org/
Interested? Contact Berndt Müller at for further information.

APPLICATION PROCEDURE:
This project is advertised in relation to the research areas of MEDICAL SCIENCES. Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php. You should apply for Degree of Doctor of Philosophy in Medical Sciences, to ensure that your application is passed to the correct person for processing.

NOTE CLEARLY THE NAME OF THE SUPERVISOR AND EXACT PROJECT TITLE ON THE APPLICATION FORM. Applicants are limited to applying for a maximum of 3 applications for funded projects. Any further applications received will be automatically withdrawn.

Funding Notes

This project is funded by a University of Aberdeen Elphinstone Scholarship. An Elphinstone Scholarship covers the cost of tuition fees only, whether home, EU or overseas.

For details of fees: View Website

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

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