The centrosome is the major cellular microtubule-organizing center (MTOC) in mammalian cells. Centrosomes are composed of a pair of barrel-shaped structures called centrioles, surrounded by a proteinaceous matrix termed pericentriolar material (PCM). Centrioles mark the site at which PCM is recruited and hence, through the control of their duplication, define the number of centrosomes present. Prior to mitosis, duplicated centrosomes need to increase sufficiently in size by recruiting more PCM leading to an increase in MT nucleation capacity, which is needed to orchestrate the assembly of a robust bipolar spindle. Centrioles have fascinated biologists ever since their discovery by Boveri in 1888, not only for their stunning 9-fold symmetry but also for their enigmatic mode of duplication and assembly. We initially defined using the nematode C. elegans as a model system, a structural and molecular pathway that regulates centriole duplication (Pelletier et al., Nature 2006). This core duplication pathway is conserved in human cells and is a focus of study in the laboratory as well as the identification of novel regulators of centriole duplication. Another keen interest of the laboratory is to understand how centrosome assemble and increase in size and microtubule nucleation capacity at the onset of mitosis. Using sub-diffraction resolution imaging, we have defined higher-order organizational properties of pericentriolar material and centriole (Lawo et al., Nature Cell Biology, 2012 and Comartin et al., Current Biology, 2013).  Thus, an important goal of the laboratory is to decipher the cellular pathways that regulate centrosome duplication and assembly, to identify novel regulators of these processes and to delineate how these novel molecules contribute to centrosome biogenesis. We have recently identified a number of novel regulators of centrosome function through proximity mapping and are currently studying them in greater detail (Gupta et al., Cell, 2015). For more information on the higher-order organizational properties of centrosomes, see our review on this topic (Mennella et al., Trends in Cell Biology, 2014).

Pelletier et al. Nature 2006
Lawo et al. Nature Cell Biology 2012
Comartin et al. Current Biology 2013
Gupta et al. Cell 2015
Mennella et al. Trends in Cell Biology 2014

Cilia are microtubule-based structures that protrude from the cell surface and participate in a plethora of developmental processes and signaling events. Disrupting their assembly and function can lead to several diseases including myriad ciliopathies. Although motile and sensory cilia are without a doubt most famous for their paramount roles in cell motility, hearing, and in cleansing the respiratory track of pathogens, it has become increasingly clear that most cell types have immotile primordial cilia referred to as primary cilia. Primary cilia are implicated in key developmental signaling events mediated by the Wnt and Hedgehog (Hh) morphogens, planar cell polarity (PCP) and are defective in signaling events leading to the onset of disease. It is therefore critical that we understand the composition of cilia and the mechanisms underpinning their assembly and how they efficiently transduce extracellular cues through various signaling pathways. Using proximity-dependent protein identification (BioID) we have recently defined a dynamic proximity interaction landscape of the human centrosome-cilium interface (Gupta et al., Cell, 2015) highlighting vast and novel functional interaction space in those areas that remains virtually unexplored. Thus, a major goal of the laboratory is leverage this information to understand the molecular mechanisms that govern cilia formation and their roles in diverse signaling pathways and the onset of human ciliopathies. For more on this topic, see our current review (Goncalves et al., Mol. Cells, 2017).

Gupta et al. Cell 2015
Goncalves et al Mol Cells 2017