Fighting Chagas Disease by genetic manipulation of nutrient pathways in Trypanosoma cruzi

The aim of this project is to discover new molecular targets for the treatment of Chagas disease, caused by the parasitic agent Trypanosoma cruzi (T. cruzi). Approximately 100 million people are at risk of this affliction, which is responsible for around 12 000 deaths per year. The disease is most prevalent throughout South and Central America where insects known colloquially as 'kissing bugs' act as vectors and pass the parasites on to humans. Due to migration, the disease is spreading to Western countries and is therefore becoming a Global health issue. Infection with T cruzi can result in fatal organ damage, with the heart being most commonly affected. Current medications carry the risk of severe side effects and require long courses of treatment without guaranteeing cure. To direct the development of safer and more effective therapies, I hope to identify and characterise critical molecular pathways that the parasite requires to survive within its host. By using a novel gene-editing toolkit, we hope to identify proteins that T. cruzi uses to obtain nutrients (particularly vitamins/minerals) from the host to satisfy its own metabolic needs. The work involved will be quantitative, including computational bioinformatics-based analyses to identify candidate genes and high throughput cellular assays for mutant screening. Any genes that show promise in cellular assays will be studied in vivo to look at effects on the whole organism physiology. As well as being potentially medically translatable, the study is interdisciplinary, since chemical and cellular invitro techniques will be combined with live fluorescence imaging and in vivo studies. The modified parasites will be monitored in small numbers of mice to observe tissue migration characteristics, burden and progression of the infection. Furthermore, ex vivo imaging will be used to look at host responses to modified parasites and to examine parasite tropism, survival and replication in different organs.

To better understand the context of my project, I am taking a module in epidemiology, which will broaden my inter-disciplinary knowledge base and skill-set. By attending regular seminars, I am learning from varying fields of research being undertaken at LSHTM and at universities across the country, which again introduces me to a range of methodology and to multiple areas of science. As I progress in this PhD and identify further skills which will benefit my project and career development, I will undertake further training as available.