Protein interactions are at the basis of all cellular processes. This project from Dr. Philip Kim and Dr. Sachdev Sidhu at the University of Toronto is developing a novel technology platform and associated methodology that can probe such interactions in a high-throughput manner. They are combining oligonucleotide chips with combinatorial chemistry and computational methods to create a powerful technology that directly scans biologically relevant interactions. Their work will result in new insights into the biology of viral infections and novel routes to treatment.
Our work in the health sector:
Developing monomeric genome-editing nuclease
June 5, 2012The ability to alter the genetic material of mammalian cells in a precise and time-effective manner will enhance our ability to understand the molecular basis of disease and facilitate treatment options. Altering the genetic makeup relies on the development of biochemical reagents that interact with DNA in a site-specific manner, with minimal interactions at unwanted sites. The lab under Dr. David Edgell and Dr. Gregory Gloor at The University of Western Ontario has recently developed a new type of molecular scissor based on the nuclease (or cutting domain) from the phage T4 protein I-TevI that is fused to the TAL effector targeting domain which encodes DNA sequence specificity. The Tev-TAL fusions promise to be more specific and smaller than existing reagents. To realize the potential of the Tev-TAL nucleases, the team is working to understand the DNA recognition “code” of the Tev-TAL scissors.
Enhanced newborn screening
June 5, 2012Newborn screening (NBS) programs represents one of the few proven strategies to prevent infant mortality and long-term disabilities associated with rare yet treatable genetic diseases. Drs. Philip Britz-McKibbin of McMaster University and Osama Aldirbashi of Newborn Screening Ontario, Children’s Hospital of Eastern Ontario, are developing novel chemical reagent for newborn screening to enhance the analytical performance and prevent infant mortality and long-term disabilities.
Bayesian analysis of next-generation sequencing data
June 5, 2012This SPARK project will develop robust statistical data analysis tools for next generation sequencing (NGS), which refers to a set of high throughput technologies for measuring signals across the genome. Dr. Theodore Perkins’ project through the Ottawa Hospital Research Institute proposes a novel approach to reconstructing genomic signals represented in NGS data using Bayesian statistics. The main features of this approach are that the team is able to put forth a best estimate of the signal, and also to quantify the uncertainty in the estimate. Quantifying uncertainty is useful for visualization of genomic signals, and is critical for comparing them under different conditions. This statistical approach will be implemented in efficient, open-source, well-documented software, for the benefit of the NGS community.
Treating epilepsy using personalized medicine
June 5, 2012Every time someone with epilepsy has a seizure there is a risk of brain damage. This is particularly true for children. Unfortunately, today’s anti-epileptic drugs simply don’t work on about one third of patients. The team led by Drs. Patrick Cossette, Berge Minassian and Jacques Michaud will identify genes that are associated with epilepsy and that are predictive of the response to various antiepileptic drugs. This will result in earlier and more effective care and potentially prevent cognitive decline in children.
Early detection of esophageal adenocarcinoma risk
June 5, 2012Chronic heartburn can damage the lining of the esophagus, leading to a condition known as “Barrett’s esophagus”. Patients with Barrett’s esophagus have a much higher chance of developing cancer of the esophagus. Until recently, the only way to diagnose Barrett’s esophagus was through endoscopy—an uncomfortable and time-consuming procedure. However, a swallowable sponge under development in the United Kingdom allows for quick and painless diagnosis of Barrett’s esophagus in a doctor’s office. The team led by Drs. Lincoln Stein and Tony Godfrey aim to supplement this test with genomic technologies, allowing doctors to follow patients over time to identify and treat those progressing to cancer. Early detection, treatment and even prevention of these cancers could save the healthcare system over $300 million a year.
Autism spectrum disorders: Genomes to outcomes
June 5, 2012Drs. Stephen Scherer, Peter Szatmari and team are using the $9.9 million LSARP funding to identify the remaining genetic risk factors for autism spectrum disorder. This ground-breaking work will mark Canada’s contribution to an ambitious international initiative that aims to sequence and analyze the genomes of 10,000 people with autism spectrum disorder. With a more complete understanding of the genetic elements of autism, doctors will be able to make earlier diagnoses, provide better, more personalized care to patients and reduce the enormous cost autism imposes on our health care system.
Enhancing care for rare genetic diseases
June 5, 2012Drs. Kym Boycott, Alex MacKenzie and team will use powerful new gene sequencing technologies to identify the genes implicated in many of the rare diseases affecting the Canadian population. Besides providing important new understanding into human disease, this $11.7 million LSARP project will yield other benefits, including: avoiding invasive procedures, stopping ineffective treatments, developing earlier and better diagnoses, devising more appropriate treatment, and predicting the chances that one of these rare diseases could be passed on to offspring. Once the disease-causing genes have been identified, researchers will test drugs that are currently on the market to identify those that might be effective against these rare diseases.
Development of a novel macrocycle compound library
June 5, 2011A University of Toronto-based research effort is developing innovative methods around an emerging class of therapeutics called macrocycles. The team has developed a novel and effective process for making linear peptides circular. Utilising an Ontario Genomics’ PBDF investment, as well as support from MaRS Innovation, the team will to further their efforts, including building a compound library and testing for important properties such as cell permeability and stability to capitalize on emerging potential in drug development.
Potential for therapeutics in cyclic peptide scaffolds
June 5, 2011In 2010, Dr. Andrei Yudin and his students at the University of Toronto found that the molecules of cyclic peptides can be readily made using novel chemistry. Funded in part by Ontario Genomics’ SPARK program, the Yudin lab has made an exciting discovery: that not only the stability of the peptides but also the ability to enter human cells is increased when circular molecules are made with their method. The team is now working to capitalize on these molecules’ ability to enter cells to program them to also kill disease-associated proteins found in infected cells–an exciting path towards real therapeutics.