Project Details
Projekt
Function of microtubule inner proteins (MIPs) in Plasmodium morphology and mechanics throughout its life cycle
Subject Area
Biophysics
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 551865026
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, we lack a 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. Therefore, we here propose to use a combination of bottom-up and top-down approaches to understand how the mechanical and material properties of various Plasmodium stages emerge. We 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 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 us to directly link (i) the biophysical properties of the molecular parts to (ii) the kinetic and mechanical behaviour of microtubule filaments to (iii) the cellular morphology and mechanics of the parasite. Thus, we will gain 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.
DFG Programme
Priority Programmes
Subproject of
SPP 2332:
Physics of Parasitism
