Project Details
Projekt
Consequences of microtubule posttranslational modifications on the physics of the parasite Trypanosoma brucei
Subject Area
Biophysics
Parasitology and Biology of Tropical Infectious Disease Pathogens
Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
Cell Biology
Parasitology and Biology of Tropical Infectious Disease Pathogens
Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
Cell Biology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 491707420
The project's overall objective is a quantitative characterization and understanding of the impact of microtubule post-translational modifications (PTMs) on the physics of the human pathogenic parasite Trypanosoma brucei, with a particular emphasis on changes in its locomotion and cellular architecture. Cell morphology and distinct locomotion of this unicellular parasite are key for survival and propagation in the mammalian host and in the insect vector. The microtubule-based cytoskeleton of trypanosomes has evolved to meet these requirements and provides the cell with a hydrodynamically optimized shape and adaptive motility. Little is known, however, how cell-intrinsic properties like differential expression and regulation of cytoskeletal elements contribute to the adaptation to varying micro-environments. Specifically, we want to interrogate the function of a set of defined microtubule PTMs (generally referred to as the 'tubulin-code') in this context since our preliminary data have already revealed a major impact of selected PTMs on the biophysical properties of T. brucei. To this end, we will generate strains deficient in enzymes catalyzing specific PTMs. These will be investigated initially at the cell-biological level, using fluorescence imaging and electron microscopy, supported by quantitative mass spectrometry and in-vitro assays. Complementing these classical approaches, the locomotion of individual PTM-deficient trypanosomes will be tracked extensively by video microscopy and analyzed quantitatively in a variety of microfluidic environments that mimic the naturally occurring habitats. Here, different flow profiles, channel geometries, fluid viscosities/viscoelasticities, and constraining obstacle courses will be tested. We expect this project to yield a comprehensive understanding on the specific impact of microtubule PTMs on the (bio)physics of T. brucei.
DFG Programme
Priority Programmes
Subproject of
SPP 2332:
Physics of Parasitism
