Developing a next generation anti-malarial targeting parasite specific RNA splicing
Co-supervisors (at the University of Glasgow):
Andrew Tobin, Professor of Molecular Pharmacology and Director of the ARC (https://www.gla.ac.uk/schools/molecularbiosciences/staff/andrewtobin/)
Ilan Davis, MVLS Professor of Spatial Biomedicine (https://ilandavis.com)
Despite the recent availability of a vaccine, there were approximately 250 million cases of malaria in 85 leading to 608,000 deaths, 80% of which are under the age of 5 (https://www.who.int/news-room/fact-sheets/detail/malaria). Whilst current frontline treatments for malaria are effective there is growing evidence of an alarming rise in resistance to these treatments. To avert the threat of a global rise in malaria cases and deaths there is a desperate need to develop novel anti-malarials with mechanisms of action that are distinct from current medicines. In work from the Tobin lab a chemo-genetic approach in living mosquitos has validated the protein kinase PfCLK3 is antimalarial target, offering a cure and transmission blocking capability. They demonstrated that PfCLK3 is a putative master regulator of RNA splicing in P. falciparum parasites and by using a tool PfCLK3 inhibitor, TMCDC-135051confirmed that inhibition of PfCLK3 kills the parasite via disruption of RNA-splicing. The Tobin lab has subsequently spun out a biotechnology company called Keltic Pharma with Bill and Melinda Gates Foundation funding to develop a radical cure for malaria targeting PfCLK3. This PhD programme will support this drug discovery effort in an interdisciplinary project that aims to further elucidate the mode of action of drugs targeting PfCLK3 and detail the mechanisms of its disruption of the RNA splicing. The Tobin lab’s expertise in molecular pharmacology and malaria, will be combined with the Davis’ labs expertise in advanced super-resolution microscopy, single molecule and cutting-edge spatial biology methods. Novel computational approaches and AI-based image analysis methods will also be deployed. The student would also have the opportunity to have a placement in Keltic Pharma.