Identifying Molecular Targets for the Development of New Anthelmintic Drugs

Supervisors: Professor Bernadette Connolly, Dr Jonathan Pettitt and Dr Berndt Mueller (Institute of Medical Sciences)

Nematode parasites exert a significant impact globally on human and animal health, having a disproportionate impact on health and economic capacity in low and middle income countries. All ruminant animals are exposed to nematodes throughout their lives resulting in >£3 billion being spent annually for the protection and treatment of these animals. Current WHO estimates indicate that more than two billion people carry nematode infections, with the majority of these corresponding to soil-transmitted gastrointestinal infections. Current treatments for nematode infections target receptors and molecules involved in neurotransmission. Although successful, the use of the same, limited set of drugs for many years has led to the inevitable development of drug resistance in parasitic nematode populations. There is thus an urgent need to develop new anthelmintics, preferably targeting a process rather than a single molecular molecule, so making resistance harder to evolve.

Our multidisciplinary team has focussed on one such process in nematodes. Spliced leader (SL) trans-splicing is an essential, conserved nematode process that is involved in mRNA maturation and regulates gene expression. In our previous work we have shown that it constitutes an ideal target for novel anthelmintics. The overall objective of this project is to understand the detailed molecular mechanism of nematode SL trans-splicing with a view towards the identification of critical protein-RNA interactions that can be used to guide the design of drugs that target the function of this complex. To this end, we have developed a number of in vivo reporting systems that allow us to identify compounds that affect SL trans-splicing and to study the subcellular localisation of proteins and RNAs involved in this process.

As well as training in nematode genetics, biochemistry and molecular biology, the project will also provide training in methods such as genome editing, imaging, in vivo and in vitro drug screening and proteomics.

Application:

Please select ’Degree of Doctor of Philosophy in Medical Sciences (Science)’ from the list of programme options in the University of Aberdeen’s online postgraduate applicant portal to ensure that your application is passed to the correct school for processing. Then manually enter the name of the supervisor(s), project title and funder (Elphinstone) in the space provided.