Genome sequencing has revolutionized our understanding of the genetic changes that lead to cancer. Unfortunately, treatment still remains in the relative Dark Ages, with decades-old treatments that can be highly toxic and that don’t consider the subtle genetic differences among each patient’s disease. Dr. Charles Boone and his team at the University of Toronto are developing AbSyn, a new technology that will identify combination therapies tailored to individual cancers. AbSyn stands for the development of antibodies (Ab), whose promise for treating cancer has been hugely under-realized, and synergistic (Syn) therapies for cancer based on these antibodies. AbSyn will change the way we prioritize and discover new cancer drugs, building a new bridge between the gap of biological understanding and the commercial drug discovery process.
Genetic abnormalities are a leading cause of death among Canadian newborns and infants. Less invasive, less expensive prenatal diagnostic techniques that are able to provide relevant information at earlier stages of pregnancy are needed. Scientists and physicians at Toronto’s Mount Sinai Hospital have developed a method to collect and isolate fetal cells non-invasively, using a technique similar to a PAP smear. Now Dr. Aaron Wheeler’s research group at the University of Toronto is developing techniques to isolate and analyze these cells for prenatal diagnosis of genetic abnormalities. If successful, these techniques could transform the way prenatal diagnosis is delivered, resulting in higher coverage of the population, reduced patient anxiety, increased medical options for at-risk pregnancies and significant reductions in healthcare costs.
Diagnostic tests based on blood samples are mainstays of the healthcare system. Adding RNA sequencing (RNA-seq) can extract more information from blood samples, including a snapshot of all the genes active in a patient’s blood cells. Such a snapshot can tell us about the current condition of the patient’s immune system, whether there are cancer cells in the blood and/or whether blood cells are fighting an infection. Drs. Michael Wilson and Adam Shlien of The Hospital for Sick Children are developing an RNA-based clinical test called SANGRE (systematic analysis of blood gene regulation in blood) that will provide unprecedented power to use RNA expression as a routine and affordable test that can better diagnose disease, disrupting clinical practice and improving the health of Canadians.
Our cells remove damaged or nonfunctional proteins through a small protein called ubiquitin, which attaches to target proteins and signals their destruction. In many diseases, ubiquitin does not work as it should. Dr. Sachdev Sidhu of the University of Toronto is using an innovative high-throughput molecular genetics engineering platform, which is unique in the world and has attracted intense interest from industry and academia, to enable the rapid and cost-effective development of highly specific and potent ubiquitin-like molecules. These molecules attach to key, cancer-associated enzymes of the ubiquitin system, to block or enhance their function. The project will enable the discovery of new drug targets, speed up drug development and generate effective anti-cancer drugs with fewer side effects, all of which should be of great socio-economic benefit to Canadians.
Often in cancer it’s the spread of the cancer to other areas of the body, a process called metastasis, that kills. This is particularly the case with two highly lethal types of cancer, medulloblastoma (MB), the most common malignant brain tumour in children, and pancreatic adenocarcinoma, the fourth leading cause of cancer deaths in Canadians. Recent results from the lab of Dr. Michael Taylor of The Hospital for Sick Children have shown that the biology of the metastases is extremely different from the primary tumour, making it unlikely that treatments developed to treat the primary tumour will work on the metastases. Dr. Taylor has teamed with Dr. Rama Khokha (Princess Margaret Cancer Centre) to develop and deploy unique tools to discover the drivers of metastasis, helping to improve survival rates of Canadians with these deadly human cancers.
Many illnesses, such as cancer or cardiovascular disease, leave physical evidence in our bodies, called biomarkers. Spotting these biomarkers early would make it possible to begin treatment with personalized, targeted therapy, or even prevent disease entirely. Solid-state nanopore-based devices can do this, but are too expensive for widespread use. Dr. Tabard-Cossa’s laboratory has pioneered a technique to fabricate nanopore devices more rapidly and at substantially lower cost than present-day technology. They are integrating the devices into a disposable cartridge within compact platforms offering comprehensive sample-in, answer-out capability. The lab is positioned to develop a point-of-care prototype that can be used in the lab and the clinic, resulting in significant economic and health benefits for Canada.
“De novo” sequencing, or constructing an individual’s genome from his or her own data alone (as opposed to comparing it to a reference genome), is a formidable task, akin to assembling a jigsaw puzzle comprising hundreds of millions of small blank pieces. Drs. Si Lok, Stephen Scherer, and their colleagues from The Hospital for Sick Children are developing a new “mate-pair” technology that would overcome the financial and logistical barriers to de novo sequencing by linking sequences to one or more other reads in precisely known orientations and distances. Mate-pair technology would create a high-resolution backbone to enable de novo sequencing to be carried out in a single simple step. This new adaptation of mate-pair sequencing is a disruptive technology that could supersede all current methods of de novo sequencing, thereby representing a leap forward in many areas of research and, ultimately, in healthcare.
Today, the Honourable Kirsty Duncan, Minister of Science, announced $32 M in federal support for 13 large-scale applied research projects that will use genomics to solve long-standing challenges. These projects, representing a total investment of $110M, look to mitigate the effects of climate change on forestry and fisheries, protect the Arctic, and support wildlife.
Boreal Agrominerals Inc. is collaborating with researchers from Wilfrid Laurier and Algoma University to identify soil that contains beneficial naturally-occurring microorganisms to enhance the benefits in amended soils. This academic-industry partnership will work to characterize the distribution of microorganisms naturally found at various mining sites from the SRC deposit near Sudbury, Ontario, and investigate the effects of mining and site characteristics on soil microbial communities based on nutrient solubilisation and plant nutrient availability.
SickKids’ Drs. Cynthia Hawkins and John Racher and NanoString Technologies are merging their individual strengths to develop additional tools for diagnosing cancer in children. Funded through Round 6 of Genome Canada’s Genomic Applications Partnership Program, they are working to create tools that will deliver key information in a targeted, cost-effective and timely way. This initial work will focus on low-grade glioma (brain tumours), leukemia and soft-tissue sarcoma, for which no comprehensive tests currently exist. This tool will improve survival times and quality of life for children with cancer, reduce healthcare costs and generate licensing revenue, which will be shared between the partners.