Reference number : GC-2017-Q1-01962, amendment number : , agreement type : G, recipient legal name : Li, Isaac (The University of British Columbia), recipient country : CA, recipient province : nan, recipient city : British Columbia|Colombie-Britannique, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : My research program aims to understand how physical forces regulate cell behaviour. Mechanical forces were recently discovered to play a vital role in the development and functioning of biological systems. Therefore, understanding and controlling mechanical forces in the cellular micro-environment provides significant opportunities for discovery and biotechnology development. Cells interact with their environment mainly through adhesion, where adhesion proteins on cell surfaces bind to receptors on other cells or materials in the environment. A particularly important area of cell adhesion research is the rolling adhesion cascade of leukocytes and circulating tumor cells, which are key processes behind inflammatory response and cancer metastasis. Although forces can now be readily measured on the whole cell scales, very little is known about the dynamics of adhesion force at the molecular level. Understanding and measuring molecular forces is one of the major challenges facing mechano-biology. In particular, little quantitative knowledge exists on the rolling adhesion force magnitude, distribution, stoichiometry, activation state, signalling, and cooperative effects at the molecular level. The lack of mechanistic details at the molecular level hinders further advances in understanding and controlling of cell behaviours. My research program aims to develop new techniques to visualize and control forces across single adhesion bonds during cell adhesion. Applying force probes I have previously developed, we will investigate the functional aspects of molecular force events in rolling adhesion cascade. Applying DNA nanotechnology, we will continue to advance and create novel molecular force probes to detect various aspects of molecular adhesion events. Understanding how molecular forces influence cell adhesion and signalling will open new directions in controlling cell behaviour beyond conventional biochemical means, enabling novel cell screening technologies. Research enabled by the proposed infrastructure will create fundamental knowledge and applied technology that will potentially benefit the Canadian health care system, biotechnology, and pharmaceutical industries., program purpose french : My research program aims to understand how physical forces regulate cell behaviour. Mechanical forces were recently discovered to play a vital role in the development and functioning of biological systems. Therefore, understanding and controlling mechanical forces in the cellular micro-environment provides significant opportunities for discovery and biotechnology development. Cells interact with their environment mainly through adhesion, where adhesion proteins on cell surfaces bind to receptors on other cells or materials in the environment. A particularly important area of cell adhesion research is the rolling adhesion cascade of leukocytes and circulating tumor cells, which are key processes behind inflammatory response and cancer metastasis. Although forces can now be readily measured on the whole cell scales, very little is known about the dynamics of adhesion force at the molecular level. Understanding and measuring molecular forces is one of the major challenges facing mechano-biology. In particular, little quantitative knowledge exists on the rolling adhesion force magnitude, distribution, stoichiometry, activation state, signalling, and cooperative effects at the molecular level. The lack of mechanistic details at the molecular level hinders further advances in understanding and controlling of cell behaviours. My research program aims to develop new techniques to visualize and control forces across single adhesion bonds during cell adhesion. Applying force probes I have previously developed, we will investigate the functional aspects of molecular force events in rolling adhesion cascade. Applying DNA nanotechnology, we will continue to advance and create novel molecular force probes to detect various aspects of molecular adhesion events. Understanding how molecular forces influence cell adhesion and signalling will open new directions in controlling cell behaviour beyond conventional biochemical means, enabling novel cell screening technologies. Research enabled by the proposed infrastructure will create fundamental knowledge and applied technology that will potentially benefit the Canadian health care system, biotechnology, and pharmaceutical industries., agreement title english : Imaging and Controlling Molecular Forces in Live Cell, agreement title french : Imaging and Controlling Molecular Forces in Live Cell, agreement number : RGPIN, agreement value : 135000.0, 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