A shape-shifting silent assassin – how does genome instability underpin Trypanosoma cruzi drug resistance and survival in vector and host?


Martin Llewellyn, School of Biodiversity, One Health & Veterinary Medicine, University of Glasgow

Panagiotis Kotsantis, Division of Biomedical and Life Sciences, Lancaster University

Richard McCulloch, School of Infection and Immunity, University of Glasgow 

Mick Urbaniak, Biomedical and Life Sciences, Lancaster University



Chagas disease is the most important parasitic in Latin America, killing 12,000 people every year. To provide context, malaria in the region kills a fraction of that number (200-400 annually). Infection with T. cruzi in Chagas disease patients is life-long. Drug treatments are limited, often ineffective at clearing parasite infection, and almost always ineffective at alleviating debilitating chronic symptoms (heart disease, GI tract abnormalities). Despite the impact of Chagas disease on human health, relatively little is known about its biology by comparison to other related human parasites - T. brucei (agent of sleeping sickness) and Leishmania (agent of Leishmaniasis). Important knowledge gaps exist around how T. cruzi adapts to environmental stressors. Addressing theses gaps could shed light on how the parasite avoids host immunity to establish persistent infections in its host, as well as how it survives drug treatment.

 DNA sequencing of T. cruzi isolates by members of the supervisory panel and others reveals a genome in a constant state of re-arrangement. The adaptive value of such genomic re-arrangements may hold the key to understanding, and addressing, many intractable aspects of T. cruzi biology. In this PhD program the student will leverage advances in genomics, genetic manipulation, animal disease models to understand how T. cruzi genomic re-arrangements may underpin long term survival in the mammalian host as well as parasite resistance to frontline and next generation drugs. An expert and experienced supervisory team is in place to support the PhD, with opportunities for research and training in Ecuador, Uruguay and Belgium.