Project 2 develops chemical biology approaches to probe and modulate the function of proteins and protein complexes, with an emphasis on components critical for centriole assembly.
Three research axes are pursued:
- Firstly, high-throughput super-resolution STORM imaging is used to uncover the precise distribution of centriolar components and post-translational modifications (PTMs) of centriolar microtubules. Moreover, cell permeable probes are developed to track centrioles in live cells.
- Secondly, the nature of centriolar tubulin isotypes and centriolar tubulin PTMs is explored. A panel of tubulin variants is synthesized, their impact in cell-free assays tested, and their structure characterized by solid-state NMR. Furthermore, monobody-based affinity reagents are developed to assay combinatorial PTMs in tubulins and chromatin.
- Thirdly, computational design is applied to improve the affinity and specificity of monobodies against centriolar proteins, as well as to design specific binders against centriolar proteins, in both cases with the aim of modulating organelle assembly.
Overall, these approaches are expected to provide novel insights into the mechanisms governing centriole assembly.