Project Leaders:   
Marco Marra, Pamela Hoodless

Involved Institutions:   
Canada’s Michael Smith Genome Sciences Centre, Terry Fox Laboratory, University of British Columbia  

Technology Applications:   
Stem cell therapies, tissue engineering

Research Funding Program:   
Competition III

GE³LS Activity:
Effects of Different Intellectual Property Regimes on Research and Development

The development of a complex organism with many cell and tissue types from one cell is truly remarkable. It requires cells to communicate and co-ordinate but there is little known about development or the genes that regulate the process. This project will examine the development of the heart, liver, and pancreas in the mouse embryo. These organs were chosen due to their close relationship in embryonic development and because their diseases cause a significant burden for our health care system. Congenital heart defects are the most common birth defect, occurring in approximately 1% of births. Liver disease and diabetes are on the rise in our population and the organs are sites of difficult to treat cancers. Plus, all three sites are potential candidates for stem cell therapy and tissue engineering. This project plans to gain an understanding of the gene expression networks that regulate development in these tissues.

Genes are turned on and off throughout development and the regulation of gene expression is required for normal development. Gaining an understanding of gene regulation during the development of tissues and organs in the embryo will impact medical therapies, from repairing congenital defects to the new technologies of stem cell therapies and tissue engineering. Before these things can be done, we must understand how organs form and therefore the gene networks that regulate the process.

In a previous project, the Mouse Atlas of Gene Expression, the researchers established a database of 200 libraries, detailing the genes expressed from different tissues and at different times of development. This is the largest source of publicly available gene expression data for mouse development and is available on their website and the Cancer Genomics Anatomy Project website operated by the National Institutes of Health in the USA.

This project will determine how the regulation of gene expression specifies organogenesis. By examining the transcriptional networks of organogenesis, there should be insight into the mechanisms that regulate the expression of genes during organogenesis.

The project will provide an in depth understanding of the mouse transcriptome during organogenesis. The researchers will generate SAGE libraries from the developing heart, liver or pancreas with the SuperSAGE technology that generates 26bp tags for the gene expression profiling experiments. Plus, the researchers will characterize novel tags to address the origin of tags that map to their regions.

The project will also identify transcriptional regulatory networks that govern gene expression. They will use chromatin immunoprecipitation coupled with SAGE to identify genome-wide binding patterns of specific transcription factors and then integrate theseis data with gene expression data to develop insight into the transcriptional networks.

The resulting data will be released through the project website, as with the previous project, but this time the researchers will also examine the impact and ethics of public data release as part of the project. Furthermore, they are extending the public accessibility beyond the scientific community by creating an “adopt a high school science class” program to provide interaction between students and researchers.