Reference number : GC-2017-Q1-02576, amendment number : , agreement type : G, recipient legal name : Côté, Jocelyn (University of Ottawa)|Côté, Jocelyn (Université d’Ottawa), recipient country : CA, recipient province : nan, recipient city : Ontario, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : Each of our cells contain in their nucleus the exact same genetic information, encoded into our DNA. However, most of our cells have distinct roles and functions in our body, as they can be part of very distinct tissues (for example, the cells from your liver are very different from the cells in your brain). It is therefore how this genetic information is decoded and processed that will vary from cells to cells, and in turn, this is largely how the incredible cellular diversity and tissue complexity is created in our body. This decoding of genetic information, which we call &lsquo;gene expression&rsquo; involves several steps and generates many intermediates along the way (including molecule known as &lsquo;messenger RNAs or mRNAs&rsquo;). The first step of gene expression is transcription, and it is by far the most studied. Our research group is interested in steps of gene expression that are after transcription, and that are thus referred to as &lsquo;post-transcriptional processes&rsquo;. 
 
For the research program described here we propose to study a family of highly conserved proteins known as &lsquo;Staufen&rsquo; proteins, for which our group has recently uncovered a new function in a post-transcriptional process termed &lsquo;splicing&rsquo; &ndash; the process by which &lsquo;mRNAs&rsquo; are produced. Staufen was first discovered in fruit flies, where it was found to be essential for proper embryonic development. Since then, homologs of Staufen have been discovered and characterized in several other organisms, including mammals, where they were found to play multiple roles along the gene expression pathway. However, a role for Staufen proteins was never explored before our work. 
 
We thus propose here a research program to systematically and comprehensively characterize this novel function of Staufen proteins in pre-mRNA splicing. As a first short-term objective, we will use a series of sophisticated biochemical approaches in order to gain a better understanding of &lsquo;how&rsquo; Staufen proteins can impact on splicing. As a second objective, we will use state-of-the-art molecular genomics approaches to precisely identify all the genes for which expression is controlled by Staufen in specific cell types, tissues and/or at various stages during mammalian embryonic and post-natal development. 
 
Overall, our studies will provide key new insights into the molecular mechanism(s) by which Staufen proteins regulate splicing. The identification of the full spectrum of splicing targets regulated by Staufen proteins will undoubtedly lead to the discovery of novel regulatory pathways crucial for normal tissue differentiation and function. These advances in knowledge will benefit the broader research community. Finally, our research program will contribute to the very specialized training of highly qualified personnel in a field that has the potential to become transformative for academia as well as the public and private sectors., program purpose french : Each of our cells contain in their nucleus the exact same genetic information, encoded into our DNA. However, most of our cells have distinct roles and functions in our body, as they can be part of very distinct tissues (for example, the cells from your liver are very different from the cells in your brain). It is therefore how this genetic information is decoded and processed that will vary from cells to cells, and in turn, this is largely how the incredible cellular diversity and tissue complexity is created in our body. This decoding of genetic information, which we call &lsquo;gene expression&rsquo; involves several steps and generates many intermediates along the way (including molecule known as &lsquo;messenger RNAs or mRNAs&rsquo;). The first step of gene expression is transcription, and it is by far the most studied. Our research group is interested in steps of gene expression that are after transcription, and that are thus referred to as &lsquo;post-transcriptional processes&rsquo;. 
 
For the research program described here we propose to study a family of highly conserved proteins known as &lsquo;Staufen&rsquo; proteins, for which our group has recently uncovered a new function in a post-transcriptional process termed &lsquo;splicing&rsquo; &ndash; the process by which &lsquo;mRNAs&rsquo; are produced. Staufen was first discovered in fruit flies, where it was found to be essential for proper embryonic development. Since then, homologs of Staufen have been discovered and characterized in several other organisms, including mammals, where they were found to play multiple roles along the gene expression pathway. However, a role for Staufen proteins was never explored before our work. 
 
We thus propose here a research program to systematically and comprehensively characterize this novel function of Staufen proteins in pre-mRNA splicing. As a first short-term objective, we will use a series of sophisticated biochemical approaches in order to gain a better understanding of &lsquo;how&rsquo; Staufen proteins can impact on splicing. As a second objective, we will use state-of-the-art molecular genomics approaches to precisely identify all the genes for which expression is controlled by Staufen in specific cell types, tissues and/or at various stages during mammalian embryonic and post-natal development. 
 
Overall, our studies will provide key new insights into the molecular mechanism(s) by which Staufen proteins regulate splicing. The identification of the full spectrum of splicing targets regulated by Staufen proteins will undoubtedly lead to the discovery of novel regulatory pathways crucial for normal tissue differentiation and function. These advances in knowledge will benefit the broader research community. Finally, our research program will contribute to the very specialized training of highly qualified personnel in a field that has the potential to become transformative for academia as well as the public and private sectors., agreement title english : Defining the Role of Staufen proteins in pre-mRNA Splicing, agreement title french : Defining the Role of Staufen proteins in pre-mRNA Splicing, 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