Reference number : GC-2017-Q1-02451, amendment number : , agreement type : G, recipient legal name : Ewart, Kathryn (Dalhousie University), recipient country : CA, recipient province : nan, recipient city : Nova Scotia|Nouvelle-Écosse, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : Proteins carry out the work of life. Most of these linear polymers must fold into specific forms in order to function. However, under stressful conditions such as temperature extremes, properly folded proteins can unfold and thereby lose their functionality. They can also then misfold, resulting in alternative non-functional forms. Species have evolved various means of preventing protein unfolding and of remedying it when it occurs. Many species in our north temperate oceans withstand temperatures that challenge stable protein folding. Therefore, these species are ideal for the study of adaptations that allow maintenance of folded, functional proteins. There is a great deal known about protein fold preservation within cells; most recently, reversible aggregation of correctly folded proteins was found to be adaptive during heat stress [10]. However, the adaptations that protect functional folded proteins in the extracellular milieu, and specifically in blood plasma, are not as well understood. Therefore, the proposed research aims to examine extracellular adaptations in a northern fish species, the winter flounder, using complementary strategies. In one approach, fold preservation will be studied in blood plasma proteins in order to identify reversible native protein aggregation and protein chaperoning by small molecules (chemical chaperones) that may alter folding. In the other approach, mechanisms of folding failure will be examined using a helical plasma antifreeze protein (AFP). As a result of specific ice binding, the AFP can convert from its functional helical structure to a misfolded aggregate referred to as amyloid. The role of ice binding in this transition will be defined. In addition, the amyloid form of AFP will be used as an endogenous template for cross-seeding of aberrant folding in other plasma proteins. The effects of natural chemical chaperones on these processes will also be examined. Together, these results will indicate the conditions under which normal folding can be maintained in winter flounder plasma proteins, along with small molecules that favour or counter it. These findings will be critical to the understanding of mechanisms by which winter flounder and other species might survive in our warming coastal environments. Furthermore, since proteostasis is disrupted and amyloids accumulate in diseases such as Parkinson&rsquo;s and Alzheimer&rsquo;s, these results may also find application in the prevention of some forms of human neurodegeneration., program purpose french : Proteins carry out the work of life. Most of these linear polymers must fold into specific forms in order to function. However, under stressful conditions such as temperature extremes, properly folded proteins can unfold and thereby lose their functionality. They can also then misfold, resulting in alternative non-functional forms. Species have evolved various means of preventing protein unfolding and of remedying it when it occurs. Many species in our north temperate oceans withstand temperatures that challenge stable protein folding. Therefore, these species are ideal for the study of adaptations that allow maintenance of folded, functional proteins. There is a great deal known about protein fold preservation within cells; most recently, reversible aggregation of correctly folded proteins was found to be adaptive during heat stress [10]. However, the adaptations that protect functional folded proteins in the extracellular milieu, and specifically in blood plasma, are not as well understood. Therefore, the proposed research aims to examine extracellular adaptations in a northern fish species, the winter flounder, using complementary strategies. In one approach, fold preservation will be studied in blood plasma proteins in order to identify reversible native protein aggregation and protein chaperoning by small molecules (chemical chaperones) that may alter folding. In the other approach, mechanisms of folding failure will be examined using a helical plasma antifreeze protein (AFP). As a result of specific ice binding, the AFP can convert from its functional helical structure to a misfolded aggregate referred to as amyloid. The role of ice binding in this transition will be defined. In addition, the amyloid form of AFP will be used as an endogenous template for cross-seeding of aberrant folding in other plasma proteins. The effects of natural chemical chaperones on these processes will also be examined. Together, these results will indicate the conditions under which normal folding can be maintained in winter flounder plasma proteins, along with small molecules that favour or counter it. These findings will be critical to the understanding of mechanisms by which winter flounder and other species might survive in our warming coastal environments. Furthermore, since proteostasis is disrupted and amyloids accumulate in diseases such as Parkinson&rsquo;s and Alzheimer&rsquo;s, these results may also find application in the prevention of some forms of human neurodegeneration., agreement title english : Protein aggregation in a variable environment, agreement title french : Protein aggregation in a variable environment, agreement number : RGPIN, agreement value : 130000.0, 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