Mennella, Vito - University of Toronto - Department of Biochemistry

研究领域

Our main interest is to discover how novel genetic mutations identified in pediatric patients at SickKids cause rare diseases of the lung and brain. We study motile ciliopathies and microcephaly, diseases with severe consequences for patients caused by impaired function of proteins that regulate centrosomes and cilia. To understand the mechanism underlying these rare diseases and how to diagnose them better we study how multiple proteins are organized together in “supramolecular assemblies” and how individual patients’ mutations affect their function. To study this level of cellular organization we use a unique and cross-disciplinary toolbox: we build nanometer-scale molecular maps of centrosome and cilia complexes by combining advanced imaging tools — e.g. super-resolution fluorescence and FIB-SEM electron tomography imaging— and we determine the role of these assemblies using functional analysis in patient-derived cells.

近期论文

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Super-Resolution Microscopy: From Single Molecules to Protein Complexes to Supramolecular Assemblies Sydor A, Czymmek KJ, Puchner EM, Mennella V. Trends in Cell Biology. 2015 Dec;25(12):730-48. Subdiffraction resolution microscopy methods for analyzing centrosomes organization. Mennella V, Hanna R, Kim M Methods Cell Biol. 2015; 129:129-52. The conserved Seckel syndrome and centrosomal protein Ninein localizes asymmetrically to stem cell centrosomes, but is not required for normal development, behavior, or DNA damage response *Zheng Y, *Mennella V, Marks S, Wildonger J, Elnagdi E, Nung Y. Jan, David Agard and Timothy Megraw Molecular Biology of the Cell, 2016 vol. 27 no. 11 1740-1752 Super-resolution Light Microscopy: SIM (Structured Illumination Microscopy). Vito Mennella Encyclopedia of Cell Biology, edited by Ralph A. Bradshaw and Philip Stahl Centriole Remodeling during Spermiogenesis in Drosophila. Khire A, Jo KH, Kong D, Akhshi T, Blachon S, Cekic AR, Hynek S, Ha A, Loncarek J, Mennella V, Avidor-Reiss T. Curr Biol. 2016 Dec 5;26(23):3183-3189 Amorphous no more: subdiffraction view of the pericentriolar material architecture. Mennella V, Agard DA, Huang B, Pelletier L. Trends Cell Biol. 2014 Mar;24(3):188-97. Subdiffraction-resolution fluorescence microscopy reveals a domain of the centrosome critical for pericentriolar material organization. Mennella V, Keszthelyi B, McDonald KL, Chhun B, Kan F, Rogers GC, Huang B, Agard DA. Nature Cell Biology. 2012 Nov;14(11):1159-68. Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome. Gopalakrishnan J, Mennella V, Blachon S, Zhai B, Smith AH, Megraw TL, Nicastro D, Gygi SP, Agard DA, Avidor-Reiss T. Nature Communications 2011 Jun 21;2:359. doi: 10.1038/ncomms1367.