Reference number : GC-2017-Q1-02189, amendment number : , agreement type : G, recipient legal name : Roux, Philippe (Université de Montréal), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : OVERVIEW OF THE PROBLEMATIC
 
The preparation of eukaryotic cells for division requires an extensive cellular reorganization, affecting cytoskeletal elements, chromatin, and organelles. These changes in cellular architecture ensure the proper segregation of chromosomes and inheritance of organelles. Defects in mitotic reorganization can affect mitotic entry, chromosome segregation, organelle inheritance, and cell fate. At mitosis entry, cells round up to generate optimal cell geometry for mitotic spindle assembly and cytokinesis. These changes are, for the most part, regulated by the central cell cycle regulator Cdk1, which controls many events affecting cell shape and cell adherence. While Cdk1 regulates nearly all intracellular events occurring during mitosis, much less is known about its potential impact at the cell surface. As with other cellular compartments, the plasma membrane undergoes dramatic reshaping at the onset of mitosis, but the global function of these changes is poorly known. While mitotic cell rounding is not fully understood, it appears to be driven by changes in the actin cytoskeleton and by the downregulation of adhesive systems. Some receptors were shown to be depleted from the surface of mitotic cells, but a more global analysis would be required to fully understand the role and regulation of cell surface proteins during mitosis.
 
 
 OBJECTIVES
 
Plasma membrane proteins have been historically understudied because of technical limitations. Chemoproteomic techniques that target the cell surface proteome (i.e., surfaceome) have begun to overcome these limitations by providing comprehensive analyses of surface-accessible protein domains. We have adapted this technology to study the role of cell surface proteins in mitosis, and have two main goals for this project:
 
 
 1) We want to generate high-resolution surfaceome maps of cells at different phases of the cell cycle. In this aim, we will use proteomic approaches, biochemical and cellular assays, to monitor cell-surface proteins during the cell cycle.
 
 
 2) We want to determine the biological significance of cell-surface changes as they relate to mitosis. In this aim, we will use cell-biological methods and microscopy to study the role of cell-surface proteins in mitosis.
 
 
NOVELTY and EXPECTED SIGNIFICANCE OF THE WORK
 
Using innovative approaches in proteomics, we expect to uncover the precise changes that occur at the cell surface during the cell cycle. These data will help define how mitotic cells reorganize the cell surface, and will likely reveal important information about this basic biological process.
Our results will be a resource for our lab and the scientific community, and will likely stimulate new investigation paths for years to come. This project will provide an outstanding platform for training the next generation of scientists on highly complex biological questions relating to the cell cycle., program purpose french : OVERVIEW OF THE PROBLEMATIC
 
The preparation of eukaryotic cells for division requires an extensive cellular reorganization, affecting cytoskeletal elements, chromatin, and organelles. These changes in cellular architecture ensure the proper segregation of chromosomes and inheritance of organelles. Defects in mitotic reorganization can affect mitotic entry, chromosome segregation, organelle inheritance, and cell fate. At mitosis entry, cells round up to generate optimal cell geometry for mitotic spindle assembly and cytokinesis. These changes are, for the most part, regulated by the central cell cycle regulator Cdk1, which controls many events affecting cell shape and cell adherence. While Cdk1 regulates nearly all intracellular events occurring during mitosis, much less is known about its potential impact at the cell surface. As with other cellular compartments, the plasma membrane undergoes dramatic reshaping at the onset of mitosis, but the global function of these changes is poorly known. While mitotic cell rounding is not fully understood, it appears to be driven by changes in the actin cytoskeleton and by the downregulation of adhesive systems. Some receptors were shown to be depleted from the surface of mitotic cells, but a more global analysis would be required to fully understand the role and regulation of cell surface proteins during mitosis.
 
 
 OBJECTIVES
 
Plasma membrane proteins have been historically understudied because of technical limitations. Chemoproteomic techniques that target the cell surface proteome (i.e., surfaceome) have begun to overcome these limitations by providing comprehensive analyses of surface-accessible protein domains. We have adapted this technology to study the role of cell surface proteins in mitosis, and have two main goals for this project:
 
 
 1) We want to generate high-resolution surfaceome maps of cells at different phases of the cell cycle. In this aim, we will use proteomic approaches, biochemical and cellular assays, to monitor cell-surface proteins during the cell cycle.
 
 
 2) We want to determine the biological significance of cell-surface changes as they relate to mitosis. In this aim, we will use cell-biological methods and microscopy to study the role of cell-surface proteins in mitosis.
 
 
NOVELTY and EXPECTED SIGNIFICANCE OF THE WORK
 
Using innovative approaches in proteomics, we expect to uncover the precise changes that occur at the cell surface during the cell cycle. These data will help define how mitotic cells reorganize the cell surface, and will likely reveal important information about this basic biological process.
Our results will be a resource for our lab and the scientific community, and will likely stimulate new investigation paths for years to come. This project will provide an outstanding platform for training the next generation of scientists on highly complex biological questions relating to the cell cycle., agreement title english : Cellular reprogramming during cell cycle progression, agreement title french : Cellular reprogramming during cell cycle progression, agreement number : RGPIN, agreement value : 170000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada