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Deciphering the mechanisms of developmentally regulated centriole elimination

Project description

Shedding light into centriole elimination during oogenesis

Centrioles are cellular organelles that support the formation of the locomotion structures cilia and flagella as well as centrosomes. During sexual reproduction, only the sperm contributes centrioles to the zygote, whereas centrioles are eliminated from the oocyte. Still, the underlying mechanism remains unknown. The EU-funded CENTEL project will employ Caenorhabditis elegans to unveil the mechanism by which centrioles are eliminated during oogenesis. Researchers will apply live imaging and conduct a proteomic screen to identify the key players in the process. Among the key objectives is to disclose the extent by which centriole elimination has been evolutionary conserved.

Objective

Centrioles are evolutionary conserved organelles that template the formation of cilia, flagella and centrosomes. Centriole number dictates how many such structures form in a cell, so that controlling this number is essential for proper development and health. During sexual reproduction of animals, only the sperm contributes centrioles to the zygote, whereas centrioles are eliminated from the oocyte. The signals initiating and the processes executing centriole elimination remain largely elusive, both during oogenesis and in other developmental contexts where this can occur. Here, I propose to conduct state-of-the art live imaging and use novel quantitative super-resolution approaches in C. elegans to uncover the timing and molecular changes during oogenesis centriole elimination. Moreover, I will decipher the role of the RNA-binding protein CGH-1 in the timing of centriole elimination through a sequencing-based approach. Furthermore, I will conduct a proteomic screen to identify and characterize novel components required for oogenesis centriole elimination in worms. In a complementary approach, I will address the potential evolutionary conservation of centriole elimination mechanisms using the protist N. gruberi, which diverged from C. elegans over a billion years ago. I propose to also analyze in detail the dynamics of the elimination process in this system using deployed molecular markers. Moreover, I will conduct a proteomic screen to identify candidate centriolar proteins directing centriole elimination in N. gruberi. Furthermore, I will develop RNAi-mediated and CRISPR/Cas9 inactivation methods to test the function of candidate proteins in centriole elimination, thus also adding an important item to the toolbox at the disposal of scientists using N. gruberi. Overall, my work is expected to reveal whether centriole elimination is an ancestral mechanisms that has been conserved across eukaryotes and uncover the underlying molecular tenets of this process.

Coordinator

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Net EU contribution
€ 191 149,44
Address
BATIMENT CE 3316 STATION 1
1015 Lausanne
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 191 149,44