Generating solutions

Proteins are large molecules responsible for the structure, function and regulation of cells. Canadian­led research over the last two decades has demonstrated that proteins interact with one another, and assemble pathways and networks within cells, which account for sophisticated cellular behaviour.

According to Tony Pawson, director of the Samuel Lunenfeld Research Institute at Toronto’s Mount Sinai Hospital, a key to understanding diseases such as cancer lies in investigating the dynamic changes in the cell’s protein interaction network. Pawson, his colleague and fellow molecular biologist Jeff Wrana, and University of Western Ontario biochemist Shawn Li, are project leaders of the Dynactome: Mapping SpatioTemporal Dynamic Systems in Humans.

This project will map protein interactions within human cells in order to determine whether diseases such as malignant cancers result not only from specific changes to individual genes and proteins, but also from changes in the entire cellular network. The project draws on important discoveries made by the research team.

For example, Pawson was the first to show that proteins interact in a regulated way through specific domains – something, which is important for normal cell organization but is taken over by cancer causing oncoproteins. Wrana is a world leader in understanding a super family of proteins, called Transforming Growth Factor Beta (TGF­ß), which plays a major role in regulating human cell growth and function, through molecular pathways. This project, drawing on international collaboration in the United States and China, represents the first large­scale effort to map dynamic interactions. It is expected to lead to new proteomic and computational technologies as well as innovative cancer therapies.

Integrated GE³LS Research: Ethical issues and guidelines relating to the crossjurisdictional use of human tissues and genetic information
GE³LS Project Leaders: Kerry Bowman, Mount Sinai Hospital

Summary

The GE³LS project team is examining ethical questions relating to the use of human tissues and genetic information, and ensuring confidentiality and protection of research subjects’ privacy. A critical review of consent documents from China, and evaluation of conformity with Canadian laws and guidelines set forth in Canada’s Tri-Council Policy Statement, Ethical Guidelines for Research involving Humans, as well as international guidelines (e.g., International Ethical Guidelines for Biomedical Research Involving Human Subjects (Council for International Organizations of Medical Sciences/World Health Organization) and the Declaration of Helsinki (World Medical Association)) will be performed. Where nonconformities exist, the team will develop and implement an enhanced consent form for future donors to the biobank from which this project obtains its human tissue samples.

In addition, international research guidelines, including those mentioned above, will be assessed with respect to how they address biobanking studies, culminating in a review that details ways that genomics and proteomics researchers can deal with different international research guidelines in this area. The finished product will examine topics such as informed consent, standards for external review, recruitment of participants, and cultural challenges related to consent. The assessment will uncover where these guidelines are uniform and where they diverge, and highlight problems associated with this in relation to international research, particularly with the ‘Dynactome’ project. We will also study problems that arise when a standard is included on one or more documents but omitted on others.