Genomic analysis of the impact of sexual recombination on the segregation of virulence genes in African trypanosomes
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Molecular. Genetics & Pop Health
Abstract
Trypanosoma brucei (T. brucei) is the causative agent of the neglected tropical disease, Human African trypanosomiasis (sleeping sickness), and Animal African trypanosomiasis (Nagana). This vector-borne protozoan parasite has a devastating impact across sub-Saharan Africa. The parasites can cause chronic, debilitating infections resulting in devastating health and economic implications.
Trypanosomes are extracellular parasites, meaning they spend their entire lifecycle continually exposed to the host's immune system. To evade host defences, trypanosomes have a highly established system of antigenic variation of their variant surface glycoproteins (VSGs). Only 1 VSG is ever expressed at any one time, but trypanosomes have a huge repertoire of VSG genes - over 2,000 gene copies. The variation is achieved by frequently switching VSG expression to evading the host immune system.
It has been shown previously that trypanosomes can undergo sexual recombination within the salivary gland of the tsetse fly vector, which will ultimately mix the VSG repertoire of the progeny. Within the genome, the VSG genes are present in large subtelomeric arrays which are notoriously difficult to assemble using current genome technologies as these regions are highly repetitive.
As the accuracy of genome technologies has improved over the last few years, particularly across repetitive regions, it has now been possible to sequence these trypanosomes genomes. The advancement of these technologies means that notoriously difficult regions to assemble (i.e. subtelomeric, highly repetitive arrays) can now be resolved more confidently than ever before.
The aim of my project is therefore to utilise various genome sequencing strategies to analyse the impact of sexual recombination on VSG genes in African trypanosomes. I aim to use a combination of long-read technologies and short read technologies to analyse the genomes of the parental T. brucei strains and map the genomes of the F1 progeny onto the parents to identify how sexual recombination has influenced the segregation of the VSG genes within the progeny.
Trypanosomes are extracellular parasites, meaning they spend their entire lifecycle continually exposed to the host's immune system. To evade host defences, trypanosomes have a highly established system of antigenic variation of their variant surface glycoproteins (VSGs). Only 1 VSG is ever expressed at any one time, but trypanosomes have a huge repertoire of VSG genes - over 2,000 gene copies. The variation is achieved by frequently switching VSG expression to evading the host immune system.
It has been shown previously that trypanosomes can undergo sexual recombination within the salivary gland of the tsetse fly vector, which will ultimately mix the VSG repertoire of the progeny. Within the genome, the VSG genes are present in large subtelomeric arrays which are notoriously difficult to assemble using current genome technologies as these regions are highly repetitive.
As the accuracy of genome technologies has improved over the last few years, particularly across repetitive regions, it has now been possible to sequence these trypanosomes genomes. The advancement of these technologies means that notoriously difficult regions to assemble (i.e. subtelomeric, highly repetitive arrays) can now be resolved more confidently than ever before.
The aim of my project is therefore to utilise various genome sequencing strategies to analyse the impact of sexual recombination on VSG genes in African trypanosomes. I aim to use a combination of long-read technologies and short read technologies to analyse the genomes of the parental T. brucei strains and map the genomes of the F1 progeny onto the parents to identify how sexual recombination has influenced the segregation of the VSG genes within the progeny.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N013166/1 | 01/10/2016 | 30/09/2025 | |||
| 2444200 | Studentship | MR/N013166/1 | 01/09/2020 | 31/05/2024 | Shannon Massey |