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Redefining Tsetse symbiont bacteria: A Trojan horse against Trypanosome transmission

Project description

Targeting tsetse symbiont bacteria to fight trypanosome transmission

African sleeping sickness caused by Trypanosoma brucei is one of the major causes of poverty on the African continent. Apart from infecting humans, it also affects the development of domesticated animal farming causing nagana, a disease that afflicts livestock. The EU-funded Trojan project proposes a conceptual development in the therapeutic approach against trypanosomosis targeting the parasite in its vector, the tsetse fly, thus fighting both sleeping sickness and nagana. The approach exploits the advances of modern molecular biology designing a new expression system to reduce or eliminate vector competence using one of the endosymbionts of the tsetse fly, the Sodalis bacteria. Interruption of the parasite transmission will contribute to a drastic reduction in the impact of trypanosomosis on the African continent.

Objective

African trypanosomiasis has been a historic scourge on the African continent and one of the major causes of poverty. It is responsible for sleeping sickness in humans and it avoids the development of agriculture based on domesticated animals where it causes Nagana. It is a neglected disease with the worst drug control according to WHO. In this project, I propose a conceptual change in the therapeutic approach against Trypanosoma sp., being the goal of the proposal to eliminate the parasite in its vector, the tsetse fly, thus fighting both, sleeping sickness and Nagana. Taking advantage of the current methodological advances, the claim of this innovative proposal is the design of a new expression system to reduce or eliminate the vector competence, using for it one of the endosymbionts of the fly, Sodalis sp. The development of this idea involves a work of entomology, microbiology, parasitology and molecular biology. For this study, 2 research groups with solid and complementary expertise and skills are required: The French National Research Institute for Sustainable Development (France) and the University of Groningen (The Netherlands). The methodology implemented in this project will be: (i) characterization of proteins secretion pathways in Sodalis for heterologous expression of peptides, (ii) identification of promoters overexpressed in Sodalis upon interaction with Trypanosoma, and their characterization by fusion to fluorescent proteins, iii) paratransgenesis assays in flies and evaluation of the in vivo activity in infected and non-infected flies, stability across time and inherency to progeny, iv) analysis of the vector competence, using the new expression system by the production of antimicrobial peptides active against Trypanosoma, production of insecticidal peptides to kill the flies infected and RNA interference with the fly/symbionts. Blocking parasite transmission, we will contribute to drastically reduce the impact of trypanosome on African health.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF-EF-CAR - CAR – Career Restart panel

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Call for proposal

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

RIJKSUNIVERSITEIT GRONINGEN
Net EU contribution
€ 187 572,48
Address
Broerstraat 5
9712CP Groningen
Netherlands
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 187 572,48