Centrioles play a key role in the assembly of the centrosome, the major microtubule organizing center, and are crucial for the formation of cilia and flagella. Significant progress has been made toward understanding centriole biogenesis, but the mechanisms that determine centriole length and prevent centrioles from forming cilia or flagella remain unknown. CP110, Cep97, Cep120, CPAP, SPICE1 and centrobin have been identified as key players in these fundamental biological processes.
The overarching aim of this research proposal is to understand how these proteins cooperate in order to control centriole length. The following unresolved questions will be addressed:
1) What is the molecular mechanism of the interactions between centriolar proteins that play a key role in controlling centriole length and cilia formation?
2) How do the proteins involved in centriole length control interact with tubulin and microtubules?
3) What is the functional importance of interactions of key proteins in controlling centriole length and cilia formation?
A multidisciplinary approach encompassing state-of-the-art bioinformatics, biochemical, biophysical, and structural and cell biology methods will be used to tackle these open questions. The results will significantly contribute to our understanding of centriole and cilia biogenesis. Ultimately, the proposed research will help to understand how misregulation of these processes leads to human diseases such as cancer, polycystic kidney disease, microcephaly, dwarfism, and primary ciliary dyskinesia.
Field of science
- /natural sciences/biological sciences/cell biology
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
- /medical and health sciences/clinical medicine/oncology/cancer
Call for proposal
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