Investigating the Dynamic Interplay between the Extracellular Matrix and Cellular Behaviour

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The Extracellular Matrix (ECM) is the structural microenvironment necessary for the physical support of the population of cells embedded within it. Once viewed as only an inert scaffold for organizing cells into tissues, the ECM has gained importance in providing essential signals through integrin adhesion molecules necessary for controlling cellular behaviour, including cell proliferation, differentiation and survival. However, the detailed molecular mechanisms governing ECM signalling have yet to be fully understood. Matricellular proteins are a recently classified group of active matrix proteins known to regulate events that modulate ECM-cellular binding and signalling. Therefore, matricellular proteins offer a novel approach to understand the details between the matrix and cellular communication.******To best recapitulate the mechanisms implicated within ECM-cellular communication, we will use fibroblasts as a cellular model since these cells have a rich response mechanism to ECM signals to produce large amounts of various matrix proteins. This fibroblast response is known as Fibroblast-To-Myofibroblast Transition (FMT) and occurs during biological processes requiring ECM remodeling, i.e. development. We recently discovered several matricellular protein genes that were upregulated in a fibroblast model of ECM remodeling. Among those genes, MGP was one of the top selected candidates and is currently being used to understand how matricellular proteins activate cellular pathways through the FMT process, but also successfully validate the approach of studying matricellular proteins for our long-term program. ******Our research program will contribute to the understanding of the fundamental concepts underlying the understudied' role of matricellular proteins in the ECM, whose signals could be as dynamic as an intracellular signalling cascade. The program also provides optimal training opportunities for innovative thinking, technological advancement and scientific discovery that will benefit Canadians and the whole scientific community. Although such discoveries would be pertinent to scientists studying molecular and cellular processes, they will also provide a basis for technological advancement in matrix engineering needed for the development of 2D-3D biomimetic materials that are ECM analogs. Overall, our MGP study will be the platform to other discovered matricellular proteins from our RNA data to build our future program in matricellular protein research.**