Investigating the role and regulation of membraneless granules for the development of T. brucei

Adaptation to a change of environment is an essential process for survival, in particular for parasitic organisms exposed to a wide range of hosts. African trypanosomes represent an excellent model for posttranscriptional gene regulation because their genome is organised into polycistronic transcription units composed of functionally unrelated genes. As a consequence, when the parasite encounters different environments during its life cycle it adapts quickly without extensive transcriptional control. Instead, mRNA turnover and translational regulation allow rapid changes in gene expression to allow developmental change. The response of trypanosomes to developmental cues culminating in the generation of stumpy forms is often considered to have similarities to the response of the parasites to stress. We have recently demonstrated that the quorum sensing driven response of the parasites generates a specific and programmed hierarchy of membraneless granule assembly, with the distinct components and their regulators, contributing to the successful execution of the necessary steps for onward life cycle development.

This work has raised several key questions such as, Is there a protein or RNA signature for the different types of granules we observed during differentiation ? What determines the targeting of relevant proteins or RNA in the respective granules ? Are differentiation granules the same (molecular signature and function) at different life stages of the parasite ?

The aim of this project is to understand the molecular regulations for the formation of differentiation granules during the T. brucei life cycle. This will require the use of a range of cutting-edge techniques such as CRISPR/Cas9 gene editing, quantitative proteomics and transcriptomics, proximity-labelling and pull-down, enzymatic assays and both in vivo/vitro imaging. This research will provide an understanding of the parasite’s life cycle and regulation of membraneless organelles formation in free living organisms. The PhD student will gain expertise in trypanosome biology, cell-signalling regulation, proteomics and transcriptomics, microscopy and host-pathogens interactions.

Our laboratories provide a supportive and collaborative environment in which the PhD student can expand their range and learn new techniques. The PhD student will also join a team of researchers in the York Biomedical Research Institute investigating cellular processes in parasites that cause African trypanosomiasis and leishmaniasis. The Department of Biology is renowned internationally for its research and strives to provide a working environment which allows all staff and students to contribute fully, flourish, and excel.

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, religion/belief, marital status, pregnancy and maternity, 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.