Understanding Stability: How Microtubules Shape the Malaria Parasite
The malaria parasite Plasmodium has a remarkable ability: at each stage of its life cycle, it adopts a different shape while withstanding considerable mechanical stress. This is made possible by its microtubule cytoskeleton—a highly dynamic network that provides the cell with structure, stability, and motility. However, it remains largely unclear how structural components located inside these microtubules, known as microtubule inner proteins (MIPs), contribute to this exceptional stability.
In the project “Function of microtubule inner proteins in Plasmodium morphology and mechanics throughout its life cycle,” the team investigates how MIPs influence microtubule dynamics and robustness and how these properties, in turn, shape the mechanical characteristics of the parasite as a whole. To address these questions, parasite microtubules are reconstituted in the laboratory from purified components and analyzed using state-of-the-art optical and biophotonic methods. In addition, different parasite stages are studied under controlled external conditions, and MIP mutants are generated to better understand how Plasmodium responds to stress and maintains its shape.
The goal is to develop a comprehensive understanding of how the molecular properties of individual microtubules influence the parasite’s cellular structure and function. These insights may help reveal the fundamental biomechanics of Plasmodium and identify new avenues for future therapeutic strategies.
Funding: German Research Foundation (DFG), projects DI 1226/11-1 and RE 3925/7-1
Project Duration: September 2026 – August 2029
Funding Amount: EUR 315,187
Principal Investigator:
Contact:
Publications:
(1) Henkin, G. & Reber, S. (2025). Microtubules: Decoding tubulin diversity with help from an amoeba. Current Biology, 35(2).
(2) Troman, L., de Gaulejac, E., Biswas, A., Stiens, J., Kuropka, B., Moores, C. A. & Reber, S. (2025). Mechanistic basis of temperature adaptation in microtubule dynamics across frog species. Current Biology.
(3) Kim, K., Biswas, A., Guck, J. & Reber, S. (2025). Measuring Molecular Mass Densities at Subcellular Resolution Using Optical Diffraction Tomography. Methods Mol Biol, 119–141.
(4) Borchert, M., Hellinga, J. R., Reber, S., Krücken, J. & von Samson-Himmelstjerna, G. (2024). Benzimidazole inhibits Haemonchus contortus microtubule dynamics by intradimer structural changes observed by in silico modeling. Journal of Biomolecular Structure and Dynamics.
(5) Reber, S., Singer, M. & Frischknecht, F. (2023). Cytoskeletal dynamics in parasites. Current Opinion in Cell Biology, 86, 102277.
(6) Hirst, W. G., Fachet, D., Kuropka, B., Weise, C., Saliba, K. J. & Reber, S. (2022). Purification of functional Plasmodium falciparum tubulin allows for the identification of parasite-specific microtubule inhibitors. Current Biology, 32, 919–926.
(7) Kletter, T., Biswas, A. & Reber, S. (2022). Engineering metaphase spindles: Construction site and building blocks. Current Opinion in Cell Biology, 79.
(8) Hirst, W. G., Kiefer, C., Abdosamadi, M. K., Schäffer, E. & Reber, S. (2020). In Vitro Reconstitution and Imaging of Microtubule Dynamics by Fluorescence and Label-free Microscopy. STAR Protocols, 1(3), 100177.
(9) Reusch, S., Biswas, A., Hirst, W. G. & Reber, S. (2020). Affinity Purification of Label-free Tubulins from Xenopus Egg Extracts. STAR Protocols, 1(3).
(10) Hirst, W. G., Biswas, A., Mahalingan, K. K. & Reber, S. (2020). Differences in intrinsic tubulin dynamic properties contribute to spindle length control in Xenopus species. Current Biology, 30(11).
