Completed Infection & Immunity Genetics & Molecular Biology

Genetic determinants of host/parasite interactions in African trypanosomiasis

Funder Wellcome Charity-funded
Associated organisations University of Glasgow · Wellcome Sanger Institute Europe PMC affiliations are not treated as award recipients or mapped locations.
Funding £1.6M
Period Oct 2011 — Jan 2018

In plain English

AI plain-English summary

Sleeping sickness parasites carry genetic differences that determine whether an infected person dies quickly or survives for years. The disease—caused by *T.b. gambiense* or *T.b. rhodesiense*—kills tens of thousands across sub-Saharan Africa. Doctors know that some people resist infection entirely while others develop severe disease, but the genetic reasons for this variation remain largely unknown. This project will compare the DNA of more than 140 parasite strains with the genes of infected people to identify which molecular interactions tip the balance between immunity and illness. If the team pinpoints the key host and parasite molecules that govern infection and disease severity, those molecules become targets for new drugs or vaccines. The project will also create a public biobank of parasite strains and a genomic sequence resource, giving other researchers tools to accelerate their own work. This is fundamental science—it will not produce a treatment tomorrow. But understanding the precise genetic handshake between parasite and human immune system is the necessary first step toward interventions that could prevent infection or control disease progression in the field.

View original technical description
The aim of this project is to examine the role of natural genetic variation in both the human host and parasite in determining the outcome of infection with either T.b. gambiense or T.b. rhodesiense. There is now a body of data, which shows there is variation in the factors that: (a) prevent initial host infection; and (b) determine disease severity. However, we have a relatively limited knowledge of the mechanisms involved and how genetic variation affects disease outcome. This proposal will ex ploit natural genetic variation to identify the key features and molecules involved using a combination of host association of candidate genes, parasite population genomics and molecular analysis of primate trypanolytic complexes present in serum. In addition, the proposal will create a large genomic sequence resource of >140 parasite strains together with a biobank of the parasites strains for those working in other areas. Thus, by dissecting some of the key components of both host and parasite which are determinants of infection and disease outcome, a series of pathways and molecules will be identified which could be the targets of novel interventions aimed at preventing or controlling the disease.

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Researchers

Annette MacLeod (EPMC Awardee)Matthew Berriman (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

The molecular basis and evolution of host-parasite interactions in African trypanosomes
Understanding host-parasite interactions of Trypanosoma parasites in skin colonisation of their mammalian hosts
Characterising the regulators of trypanosome development and virulence in selected and natural parasite isolates
The impact of gastrointestinal helminths on susceptibility to African trypanosome infections
Expression profiling of African trypanosomes in human and primate hosts: Identification of biomarkers for diagnosis, drug target identification and dissection of virulence pathways.

Original classification

Senior Research Fellowship Basic

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