Fully-funded White Rose BBSRC DTP Biology project: Structural and functional dissection of the molecular machinery responsible for singular antigen expression and immune evasion in African trypanosomes

Lead supervisor: Dr Joana Correia Faria (Department of Biology)

Co-supervisors: Dr Jamie Blaza (Department of Chemistry) and Prof Jeremy Mottram (Department of Biology)

The student will be registered with the Department of Biology 

In the host-pathogen arms race, antigenic variation is one of the most sophisticated virulence mechanisms. Some of the deadliest parasites, like African trypanosomes and malaria parasites, are able to systematically alter the identity of proteins displayed to the host immune system, causing high mortality and morbidity among the world's poorest populations. Notably, antigenic variation has greatly challenged vaccine development against these organisms.

Trypanosomes are masters of disguise, expressing their variant surface glycoprotein in a monogenic fashion from thousands of possible genes – a fine example of extreme biology and a great model system. The pursuit for the machinery responsible for singular antigen expression has been a 50-year long quest and had remained elusive in every organism. Its recent identification in trypanosomes ((PMID: 31289266; 33432154) represents a timely opportunity to crack this long-standing mystery.

 This project aims to:

-purify this novel protein complex and solve its tridimensional structure by cryoEM, which will be critical to understand its mechanism of action.

-identify key post-translational modifications and characterise their functional/regulatory role.

 Therefore, the successful applicant will be trained on several cutting-edge technologies, including gene editing (CRISPR/Cas9), mass-spectrometry, next-generation sequencing, protein purification in native conditions and cryoEM.

 Notably, understanding the molecular mechanisms underpinning antigenic variation is invaluable, as it greatly challenges vaccine development against several organisms.

 The supervisors have combined expertise in trypanosomes’ molecular and cell biology, post-translational modifications and isolation/purification of complexes from endogenous sources for cryoEM analysis. This expertise as well as access to key enabling technologies at the University of York (miniaturised protein purification systems; the York cryoEM and Proteomics facilities) will greatly accelerate the proposed research.

 The primary supervisor is a new PI and is herself still in the lab therefore providing ‘hands-on’ training.

 To find more information about us, please check:

https://joanacorreiafaria.wixsite.com/faria-tryps-lab/about

https://www.york.ac.uk/chemistry/staff/academic/a-c/jblaza/

https://www.mottramlab.org

The Departments of Biology and Chemistry both hold an Athena SWAN Gold Award. We are committed to supporting equality and diversity and strive to provide a positive working environment for all staff and students. 

The WR DTP and the University of York are committed to recruiting 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 we 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 any biological, chemical, and/or physical science backgrounds, or students with mathematical background who are interested in using their skills in addressing biological questions. 

Programme: PhD in Mechanistic Biology (4 years)

Start Date: 1st October 2023

Interviews: Friday 10 February 2023 or Monday 13 February 2023. Please keep these dates free.