Deciphering the functional regulation of pericentrosomal structures in C. elegans

• Applicant: Dr. Tamara Mikeladze-Dvali
• Subject Area: Cell Biology ; Developmental Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 537514469

Centrosomes are the main microtubule organizing centers of animal cells which ensure spindle bipolarity during cell division. An error-free regulation of centrosome component homeostasis is therefore essential for human health. In recent years several pericentrosomal structures, such as centriolar satellites and aggresomes have been identified in vitro in cultured cells. The function of these pericentrosomal structures remains speculative however it is emerging that crosstalk between the centrosomes and their surrounding structures is essential for the proteostasis of centrosome components. The model organism C. elegans is instrumental in the discovery and molecular characterization of centrosomal components in a living multicellular organism, but surprisingly pericentrosomal structures have not been identified yet. We were able to close this gap by discovering the first pericentrosomal granular structure in C. elegans and showing that they form a distinct layer that is sandwiched between the centrosome and a surrounding specialized endoplasmic reticulum, the centriculum. Our goal is to decipher the functional cross-regulation between the centrosome and its surrounding structures in order to understand its implication for disease and the development of a multicellular organism. Towards this goal we propose to delineate the nature of the novel pericentrosomal structures, to establish an interactome of the granular layer, and to identify molecular regulators of the pericentrosomal structures. Taken together this work will pave the road towards a better understanding of molecular mechanisms regulating centrosome protein homeostasis and their function on the organismic level.

• DFG Programme: Research Grants