The use trypanosomes to uncover the identity of proteins, and their precise temporal order of recruitment, required for basal body duplication

Centrioles and basal bodies are microtubule-based organelles that assemble cilia and flagella and are conserved throughout eukaryotes. They are also important for organising mitotic spindles in dividing cells to allow chromosome segregation. Cilia/flagella are used for motility and sensory functions; for example in sperm, kidney or retinal cells. Furthermore, a group of diseases, called ciliopathies, has been linked to defects basal body duplication leading to impaired construction of cilia/flagella. Research on mutations which lead to these defects has provided us with information regarding the mechanism of basal body duplication.
Trypanosoma brucei is a single-celled protozoan parasite which uses its long flagellum for motility and sensing, therefore requiring the correct assembly of this organelle to survive. Trypanosomes are excellent models to study basal body duplication and flagellum elongation; these processes are very well controlled and occur in every cell cycle. Moreover, trypanosomes also cause disease in humans and cattle.
The aim of this project is to use trypanosomes to uncover the identity of proteins, and their precise temporal order of recruitment, required for basal body duplication to occur. By using a high-throughput gene tagging system, I will carry out a large screen on basal body proteins to identify which proteins duplicate first. This will be followed by characterisation of protein function by depleting the protein from cells and see if it has any lethal effects on basal body duplication. Findings from this study may also become relevant for understanding the process of basal body duplication in other organisms.

Priority Area
WUB, ENWW