Function of microtubule inner proteins (MIPs) in Plasmodium morphology and mechanics throughoutits life cycle

The ability of the malaria parasite Plasmodium to adopt specialised shapes for each stage of its life cycle, to resist deformation, and to proliferate largely depends on its microtubule cytoskeleton, an interconnected network of tubulin polymers and regulatory proteins. While it is generally assumed that microtubules are essential for the structural integrity of Plasmodium, there is no direct link between the mechanical properties of Plasmodium microtubules and how they contribute to the mechanics of the parasite as a physical entity. Furthermore, it remains unknown whether and how microtubule inner proteins (MIPs), which bind to the microtubule lumen, contribute to microtubule stability and the mechanical properties of the parasite on a cellular level.

The study will reconstitute Plasmodium microtubules in the presence of MIPs using purified components, systematically quantify the effect of MIPs on microtubule dynamics and mechanics using high-resolution optical microscopy at the single-filament level, and measure the bulk material properties of different parasite stages using advanced biophotonics. Challenging microtubule stability by mimicking specific environmental changes and generating MIP mutants will allow a direct link between (i) the biophysical properties of the molecular parts, (ii) the kinetic and mechanical behaviour of microtubule filaments, and (iii) the cellular morphology and mechanics of the parasite.

This approach will provide a comprehensive and quantitative picture of how Plasmodium uses an evolutionarily conserved luminal mechanism for the extraordinary stabilisation of its microtubule cytoskeleton and how this contributes to the overall mechanics of the parasite to confer cellular form and function.

Project details

Basic Science
Enabling Technologies & Assays

Jan 2025

Germany