The human body is composed of trillions of cells that play specialized roles, from fighting infections, to transmitting nerve signals or forming a protective barrier to the environment. In order to carry out these many functions, cells need to organize their inner components, including organelles (e.g. the nucleus, mitochondria) and different kinds of molecular ‘machines’, at precise locations inside the cell. When this organization is defective, it can prevent cells from working properly and predispose individuals to developing different diseases, such as neuromuscular disorders and cancer.

Our laboratory seeks to understand how cellular organization is influenced by the subcellular localization of ribonucleic acids (RNA), essential molecules involved in diverse cellular processes that also serve as carriers of the genetic blueprint for protein synthesis. Indeed, the intracellular trafficking and localized-translation of messenger RNA transcripts has emerged as a key mechanism for dictating protein distribution in cells. By analogy to global postal services or the transit systems of large cities, RNA localization is dictated by a complex network of ‘zip-code’ targeting elements residing within the RNA molecule, which are recognized by transport machineries containing RNA binding proteins (Figure 1).

Our lab aims to:

  1. Dissect the mechanisms by which RNAs are localized to precise subcellular destinations.
  2. Understand the impact of RNA localization pathways on normal cellular physiology.
  3. Determine how these processes become misregulated in disease.

For our studies, we employ a combination of human cellular models, as well as an experimentally powerful in vivo model system, the fruit fly Drosophila melanogaster. Indeed, insights gained from studying genetically tractable model organisms, such as fruit flies, have been instrumental in understanding many essential cellular processes and disease mechanism. We combine the versatility of Drosophila genetics with high-throughput molecular imaging and functional genomics approaches, as well as bioinformatics strategies.

Some of our ongoing projects and funding sources are listed below:

  1. Defining the mechanisms and functions of mRNA targeting to the mitotic apparatus. Funded by the Canadian Institutes of Health Research (CIHR).
  2. Epithelial cell polarity regulation by localized mRNAs. Funded by the Canadian Cancer Society Research Institute.
  3. Defining the mechanism of RNA incorporation within cancer cell-derived extracellular vesicles. Funded by the Cancer Research Society (team project with Janusz Rak and Nada Jabado).
  4. The roles of MBNL proteins in the pathogenesis of myotonic dystrophy. Jointly funded by Muscular Dystrophy Canada-The Rachel Fund and CIHR (team project with Pascal Chartrand and Marlene Oeffinger).
  5. Comprehensive analysis of function RNA elements encoded in the human genome. This project is part of ongoing efforts within the ENCODE consortium (team project with Brenton Graveley, Gene Yeo, Xiang-Dong Fu and Chris Burge). Our labs main contribution involves the systematic characterization of the subcellular distribution properties of human RNA Binding Proteins (see the RBP Image Database website for more details).

For more information about our work, or if you would like to join our team, please contact Dr. Lécuyer or consult the contact section of the website.

On the left are pictures of our laboratory and some of the equipment that we use for our work. By combining these diverse experimental strategies, we aim to further understand the impact of mRNA localization pathways on normal physiology and how these become deregulated in disease.