Reference number : GC-2017-Q4-01038, amendment number : , agreement type : G, recipient legal name : Leonenko, Zoya (University of Waterloo), recipient country : CA, recipient province : nan, recipient city : Ontario, recipient postal code : nan, program name english : DND/NSERC Discovery Grant Supplement, program name french : Supplément aux subventions à la découverte MDN-CRSNG, program purpose english : Cellular membrane is a fundamental unit of life and consists of nanoscopic, highly dynamic rafts composed of condensed lipids, cholesterol, and membrane proteins. These rafts are a major aspect of cell organization and central to the communication of cells with their environs. Real biological membranes are very complex and synthetic lipid bilayers or model lipid membranes are therefore widely used to mimic them in biophysical studies. The main goals of my research program are two-fold: 1) to discover novel phenomena in the biophysics of model lipid membranes, design complex and biologically relevant model membranes and elucidate the molecular mechanism of membrane interactions with charged peptides. This will provide a fundamental platform for understanding the molecular mechanism of amyloid toxicity in Alzheimer s disease (AD) and the mechanism of antimicrobial action; and 2) to develop novel membrane-based biosensing platforms, by merging lipid membrane with nanofabricated plasmonic substrates. Studying the nanoscale structure of model membranes, which mimic neuronal membranes are important for the understanding of the molecular mechanisms of amyloid binding to the membrane and amyloid toxicity in AD. I propose to investigate the similarities and differences between amyloid and antimicrobial peptides in order to expose the fundamental molecular mechanisms of their interactions with lipid membranes. My group will elucidate the effects of lipid composition and cholesterol that induce domain formation and change electrostatic heterogeneity in the lipid membrane. To tackle these problems, we will combine atomic force microscopy (AFM), atomic force spectroscopy (AFS), frequency modulation Kelvin probe force microscopy (FM-KPFM), Black Lipid Membrane (BLM) and plasmonics methods, including surface Plasmon resonance (SPR) and surface enhanced Raman spectroscopy (SERS). These advanced physical methods will be used to test my hypothesis that the membrane nanoscale structure is a dynamic property which plays an active and decisive role in its interactions with charged peptides. We will develop protocols to attach model lipid membrane to metallic nanostructured substrates and use SPR and SERS methods to monitor real time peptide-lipid interactions quantitatively and with high sensitivity. This will open new directions in biosensing applications allowing for monitoring membrane &ndash; proteins interactions for various applications. The proposed research program will advance knowledge in the areas of membrane biophysics, will provide further insight into the role of nanoscale membrane structure in amyloidal and antimicrobial peptides action and will serve as platform for the development of novel biosensors for protein detection. Furthermore, my research program will provide an excellent interdisciplinary training opportunity for multiple trainees of all levels., program purpose french : Cellular membrane is a fundamental unit of life and consists of nanoscopic, highly dynamic rafts composed of condensed lipids, cholesterol, and membrane proteins. These rafts are a major aspect of cell organization and central to the communication of cells with their environs. Real biological membranes are very complex and synthetic lipid bilayers or model lipid membranes are therefore widely used to mimic them in biophysical studies. The main goals of my research program are two-fold: 1) to discover novel phenomena in the biophysics of model lipid membranes, design complex and biologically relevant model membranes and elucidate the molecular mechanism of membrane interactions with charged peptides. This will provide a fundamental platform for understanding the molecular mechanism of amyloid toxicity in Alzheimer s disease (AD) and the mechanism of antimicrobial action; and 2) to develop novel membrane-based biosensing platforms, by merging lipid membrane with nanofabricated plasmonic substrates. Studying the nanoscale structure of model membranes, which mimic neuronal membranes are important for the understanding of the molecular mechanisms of amyloid binding to the membrane and amyloid toxicity in AD. I propose to investigate the similarities and differences between amyloid and antimicrobial peptides in order to expose the fundamental molecular mechanisms of their interactions with lipid membranes. My group will elucidate the effects of lipid composition and cholesterol that induce domain formation and change electrostatic heterogeneity in the lipid membrane. To tackle these problems, we will combine atomic force microscopy (AFM), atomic force spectroscopy (AFS), frequency modulation Kelvin probe force microscopy (FM-KPFM), Black Lipid Membrane (BLM) and plasmonics methods, including surface Plasmon resonance (SPR) and surface enhanced Raman spectroscopy (SERS). These advanced physical methods will be used to test my hypothesis that the membrane nanoscale structure is a dynamic property which plays an active and decisive role in its interactions with charged peptides. We will develop protocols to attach model lipid membrane to metallic nanostructured substrates and use SPR and SERS methods to monitor real time peptide-lipid interactions quantitatively and with high sensitivity. This will open new directions in biosensing applications allowing for monitoring membrane &ndash; proteins interactions for various applications. The proposed research program will advance knowledge in the areas of membrane biophysics, will provide further insight into the role of nanoscale membrane structure in amyloidal and antimicrobial peptides action and will serve as platform for the development of novel biosensors for protein detection. Furthermore, my research program will provide an excellent interdisciplinary training opportunity for multiple trainees of all levels., agreement title english : Nanoscale structure of lipid membrane and its role in membrane-mediated interactions, agreement title french : Nanoscale structure of lipid membrane and its role in membrane-mediated interactions, agreement number : DGDND, agreement value : 120000.0, agreement start date : 2018-01-10, 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 2020-2021)., additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier (2017-2018 à 2020-2021)., 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