Donnelly Teams Sweep National Funding Grants
Five Donnelly Centre teams have won Genome Canada’s Disruptive Innovation in Genomics grants in support of research projects totalling more than $6 million. The competition was set to boost development of technologies that have a potential to transform and speed up the commercialization of biomedical discovery.
Professors Sachdev Sidhu and Igor Stagljar received advanced Phase Two grants — the sole two grants awarded in Ontario — to further advance their technologies for the study of disease-related proteins. Stagljar was also awarded an early stage grant, along with Professors Charlie Boone, Jason Moffat and Andrew Emili for proposals that tackle how genes and proteins work together in human cells.
The awarded projects will advance our understanding of genetic and protein networks. Genes code for proteins, which make up our cells and do most of the work in them. But no protein acts alone, and it is when these molecular interactions are disrupted that disease occurs. The trick is then to find the Achilles Heel of the disease and target it selectively in a way that does not harm healthy cells and tissues.
Recent advances in genomic technologies have allowed scientists to hunt for genetic causes of diseases faster than ever before. With Genome Canada’s support, these Donnelly teams will develop new ways of finding precise molecular antidotes to target diseases, including cancer.
Boone and Moffat teams, in collaboration with Professor Brenda Andrews’ group, will use the genome editing CRISPR technology to hunt for genes in cancer cells that help tumours evade available treatments. Working together with Sidhu, they will create selective, protein-based compounds to block the molecules that give cancer its competitive edge in order to stall its growth. These compounds can then be further developed to be tested on patients, together with already available drugs, as combination therapies.
With previous funding from Genome Canada, Sidhu and Moffat have already established a platform for generating protein-based drugs to target disease proteins found at the cell’s surface. In less than six years, they have created hundreds of anti-cancer compounds, and many of these have been licensed or partnered with the pharmaceutical industry through the University of Toronto’s Centre for Commercialization of Antibodies and Biologics (CCAB), which was co-founded by Sidhu and Moffat in 2014. Several of these compounds are on track to reach the clinic as early as 2018. The current grant will allow Sidhu to expand the strategy to also include proteins that are found inside cells.
Stagljar’s team will tackle membrane proteins, which are tucked inside a layer that surrounds each cell and its inner compartments, and which are often mutated in cancer and many other diseases. The researchers will expand their technology for detecting membrane protein interactions to include every type of human cell. This will then allow them to identify those interactions that only occur in a disease state and screen for compounds that selectively block them in search of new treatments - an approach that was already shown to work for the most common type of lung cancer.
The awarding of Phase Two grants was conditional on the researchers securing two thirds of total project costs from external sources. Both Sidhu and Stagljar have raised the funds through their start-up companies, Ubiquitech and Protein Network Sciences, respectively, with Stagljar also securing support from Genentech, a pharmaceutical giant based in San Francisco.
To gain a thorough view of each protein’s whereabouts in cells, Emili’s team will build a new sub-microscopic imaging technology for studying each and every one of the many millions of individual protein molecules in human cells and tissues in unprecedented detail. This will allow scientists to understand how biological systems work at the molecular level and will provide clinicians with a tool to diagnose diseases like cancer faster and more accurately.
Genome Canada is a not-for-profit organization, funded by the Government of Canada, that supports research in genomics and development of genomic technologies. Learn more about Genome Canada here.