Project Reference: TRG27-PAT-AM1

Project title: How do parasites remodel their flagella? Exploring mechanisms of parasite adaptation through structural cell biology.

Project outline

Cilia/flagella are highly conserved cellular machines that enable eukaryotes to move, sense and respond to their environment. Some of the world's most important eukaryotic pathogens, including parasites responsible for malaria, sleeping sickness and leishmaniasis, have remodelled these organelles in striking ways to support their specialised lifestyles.

How has a conserved cellular machine been adapted during parasite evolution? And what molecular innovations allow parasite flagella to function in such diverse ways?

This project will address these questions by comparing flagellar systems across divergent eukaryotic parasites, including kinetoplastids (Leishmania and Trypanosoma) and apicomplexans (Plasmodium). The student will use an integrative structural cell biology approach spanning molecular prediction to mechanism and cellular function. The project builds on the primary supervisor's established track record in parasite flagellar motility and structural cell biology, providing the experimental platforms required to connect molecular structure with cellular function.

AI-assisted structural prediction will generate hypotheses about parasite-specific proteins. Candidate proteins will be investigated using recombinant protein expression and biochemical reconstitution. Genome-editing and live-cell fluorescence microscopy will establish their functions within parasites, while quantitative imaging and in vitro motility assays will reveal how molecular changes influence flagellar behaviour. Finally, cryo-electron microscopy and tomography will provide molecular views of these machines and their organisation within the flagellum.

By combining evolutionary comparisons with experiments spanning molecules to whole cells, the project aims to reveal fundamental principles governing the diversification of one of the most conserved organelles in eukaryotic biology, while uncovering parasite-specific adaptations that may provide new opportunities for therapeutic targeting.

Principal Supervisor

Dr Aakash Mukhopadhyay

Email address: agm85@cam.ac.uk

Department / Partner Institute: Pathology

Website: https://www.path.cam.ac.uk/research/microbiology-and-parasitology/mukhopadhyay-group

BBSRC strategic theme

Understanding the rules of life