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Self funded BMS Project : A nuclear enterprise: characterisation of an antigen expression factory for immune evasion in African trypanosomes


   York Biomedical Research Institute

  Dr Joana Faria,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Applications accepted for PhD Only

Antigenic variation is a highly sophisticated virulence mechanism. Several pathogens, such as African trypanosomes and malaria parasites, are able to systematically alter the identity of proteins displayed to the host immune system.

Monogenic expression, the ability to express a single antigen at a time, is detrimental for successful antigenic variation, however, not fully understood in any system. Recently, a novel chromatin-associated protein complex that sustains singular-antigen-expression has been identified in trypanosomes (PMID:31289266); it includes an enigmatic and very large RNA-helicase designated VEX2. In simple terms, by restricting access to RNA maturation, VEX2 excludes all but one antigen-coding-locus (PMID:33432154) – but how does any protein do that? Recently, liquid–liquid phase-separation (LLPS) has been proposed as a major regulatory mechanism underpinning the formation of membraneless bodies that compartmentalise cellular functions, such as transcription and splicing; further, a family of RNA helicases has been implicated in such phase-transitions.

In this context, the project aims to:

-Investigate a role for VEX2 in establishing a phase-separated sub-nuclear compartment;

-Identify and characterise its functional domains;

-Identify the determining factors responsible for its recruitment to specific DNA sites.

For this purpose, several state-of-the-art technologies will be applied, including gene editing (CRISPR/Cas9), next-generation sequencing and cutting-edge imaging techniques including FRAP, single molecule imaging, super-resolution and ultra-structure expansion microscopy – a rich combination of Cell and Molecular Biology, Gene Expression and Biophysics.

The molecular understanding of mechanisms underpinning antigenic variation is invaluable as it sustains persistent infections by some of the deadliest parasites and greatly challenges vaccine development against these organisms.

The York Biomedical Research Institute at the University of York is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions. 

Programme: PhD in Biomedical Science (3 years)

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Funding Notes

This is a self funded research project. Applicants need to have adequate funds to meet the costs of a self-funded research project including tuition fees and living expenses for the duration of the research programme.

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