Funding award for new Independent Investigator Manu De Rycker

Manu De Rycker is Head of Translational Parasitology in the Drug Discovery Unit (Division of Biological Chemistry and Drug Discovery) and leads the kinetoplastid diseases drug discovery portfolio. His team develop and run an extensive suite of cell-based assays for the malaria parasite Plasmodium falciparum and the intracellular parasites Leishmania donovani and Trypanosoma cruzi. These assays are pivotal for neglected tropical disease drug discovery efforts in Dundee and worldwide.

T. cruzi   is the causative agent of Chagas disease, a major infectious disease in Latin America, where it is the most common cause of non-ischemic cardiomyopathy. Current treatments are limited and come with significant side-effects. A key challenge for developing new therapeutics for Chagas disease is that the ideal drug must eradicate all parasites from the patient, including hard to kill quiescent persister parasites. Very little is known about these persisters, or heterogeneity within the parasite population in general. The aim of Manu’s work is to increase our understanding through single-cell transcriptomics experiments and identify markers, and potentially new drug targets.

Manu said: “Chagas disease is a very challenging problem from a drug discovery perspective as the parasites are intracellular, disseminate throughout the body and are difficult to kill, in particular the quiescent forms. Through phenotypic screening we have found only a handful of compounds that offer the potential to deliver new therapeutics. I am therefore very excited to start a research project to increase our knowledge of persister parasites. In all likelihood these forms will have significantly reduced transcriptional and metabolic activity and finding the key pathways that are essential for their viability will offer new avenues for drug discovery. Identification of marker genes will also help with our in vitro drug screening assays as well as understanding the role of persisters in animal models of Chagas disease.”

The project will be carried out in collaboration with Professor Kevin Read at the University of Dundee and Dr Thomas Otto from the Institute of Infection, Immunity & Inflammation at the University of Glasgow. A new postdoctoral fellow, Marta Garcia Sanchez has joined Manu’s group to work on this project.