Project description
Understanding centriole/basal body repurposing
Centrioles, components of microtubule organising centres (MTOCs), are ancient microtubule-based organelles that form the poles of the mitotic spindle. After mitosis, they can be modified as basal bodies, other ancient microtubular organelles located near the plasma membrane. Basal bodies form the template for assembly of cilia important in cellular signalling, fluid movement and locomotion. Defects in centriole/basal body repurposing can have serious effects such as infertility due to impaired sperm mobility. With the support of the Marie Skłodowska-Curie Actions programme, the MTOControl project aims to investigate the spatiotemporal control of repurposing, how the different functions evolved and why different MTOCs are not present in the same cells.
Objective
Microtubule-organizing centers (MTOCs) are key eukaryotic structures for microtubule nucleation and organization. Many MTOCs contain centrioles, organelles with two critical functions. i) In mitosis, they localize to the pole of the mitotic spindle aiding its organization. ii) After cell division, centrioles are repurposed as basal bodies at the plasma membrane where they are essential for cilia/flagella formation. Defects in centriole/basal body (CBB) repurposing can have devastating consequences and lead e.g. to infertility in human sperm. CBB functions correlate with subcellular localization, but is the spatiotemporal control required for this organelle to fulfill two distinct functions? How did the ancestral CBB evolve these functions? And why are different MTOCs not present simultaneously in a cell? To tackle these questions, I will first analyze and compare CBB repurposing strategies during the cell cycle of the green alga Chlamydomonas rheinhardtii with those in the complex life cycle of the acellular slime mold Physarum polycephalum, two evolutionary distant eukaryotes. To do so, I will develop and apply a correlative microscopy workflow in which time-lapse imaging of cells is followed by cryo-fixation and expansion microscopy (Cryo-ExM) combined with Stimulated Emission Depletion (STED). Using transient overexpression and laser ablation, I will interfere with spatial and temporal control of CBB repurposing to elucidate the role of subcellular location of this bifunctional organelle. Further, I will study how cells cope with several different MTOCs at a time, likely competing for tubulin. This project will provide a novel, high-end correlative live-cell and super-resolution imaging pipeline, which can be easily adapted for various species and cellular structures. Understanding the different strategies of CBB repurposing that evolved will have broad implications as a basis to understand CBB defects in the human cell cycle and during spermatogenesis.
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology phycology
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences physical sciences optics laser physics
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2022-PF-01
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69117 Heidelberg
Germany
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