Most mammalian cells contain tiny hair-like structures called cilia or flagella. These structures, once thought to be vestigial, have emerged as one of the key players in regulating diverse cellular functions. Cilia and flagella play a variety of roles in cellular signalling, chemo- and mechanosensing, organogenesis, cell and tissue homeostasis (non-motile primary cilia), as well as fluid flow and motility (motile cilia and flagella). All cilia are assembled around microtubule-based structures, the axonemes.
Despite their unique structure and function, axonemal microtubules are assembled from similar tubulin units as other cellular microtubules. Thus, one long-standing question is how do the microtubules adapt to their unique functions in cilia and flagella. One possible mechanism is through the posttranslational modifications (PTMs) of tubulin, which are key components of the ‘tubulin code’ which currently emerge as main regulators of MT properties and functions. The mechanism of how these tubulin PTMs regulate cilia and flagella functions is barely understood.
We are interested in understanding how specific posttranslational modifications of tubulin control diverse molecular processes within cilia and flagella, and how this in turn assures the physiological functions at cellular, organ and organism levels. The long-term goals of my team is to determine how defects in enzymes responsible for specific tubulin PTMs affect cilia function, thus leading to diverse human pathologies, called ciliopathies. Understanding these mechanisms can pave the way to future therapeutics.
We undertake a synergistic approach that involves in vitro, in cellulo and in vivo approaches combining biochemical, cell biology, molecular biology and proteomics to address the diverse questions