The Systems Biology Training Program
The Integrative Approaches to Breast Cancer Team employs systems biology approaches to tackle breast cancer. Led by Dr. Morag Park, and including Drs. Muller, Siegel, Giguère, and Hallett, this team project involves laser capture microdissection from human breast cancer tissue, gene expression microarrays, statistical analysis of gene expression correlated with prognosis, and protein biochemistry of selected targets. The project involves cutting edge histology, microarray technology, and in depth bioinformatics, combined with techniques of traditional biochemistry and genetics. The team works closely with a number of clinicians in the Montreal area, thus ensuring a flow of information and expertise between the lab and the clinic. This integrated approach has resulted in the identification of a novel set of biomarkers of disease progression that correlate with patients' clinical outcome. These findings will allow a major improvement in breast cancer therapy and an improvement in overall health for patients.
The Disease to Therapy Team is applying systems biology to the development of novel therapies for a number of so-called “orphan diseases”, principally cystic fibrosis (CF). Led by Dr. David Thomas and including Drs. Hanrahan, Hallett, Lukacs, Gehring, and Shore, this team project involves a multitude of techniques from chemistry, biology, and bioinformatics to better characterize and understand the mutation underlying the majority of CF cases. This project involves fluorescence microscopy to visualize the mutated protein at the cell surface, NMR to understand the structural elements of the mutation, and high-throughput screening of small molecule libraries to identify drug candidates to correct the defect. Gene expression arrays and advanced bioinformatic analysis are employed to better understand the pathways involved. Finally, lead compounds are tested by a variety of techniques – from traditional tissue-based physiological assays to whole-animal genetic mouse models to assays involving primary clinical samples. This project involves a large number of clinical collaborators, thus allowing for a feedback between the lab and the clinic.
The Complex Traits Group is using systems biology to understand the intricate interplay between genes and environment in the causes of human illness. Led by Dr. Philippe Gros, and including Drs. Vidal, Blanchette, and Malo, this team project combines techniques from classical genetics and biochemistry with cutting edge methods in proteomics, genomics, and bioinformatics to investigate poorly understood but deadly diseases like malaria, tuberculosis, Legionnaires’ disease and candidiasis. Recent work by the Complex Traits group identified an underlying genetic defect responsible for spina bifida, the second most common human birth defect. The group uses mice with demonstrated disease susceptibility to identify genes involved, and then characterizes these genes with a range of biochemical techniques and microarray approaches. Gene targeting with siRNA allows the group to probe the molecular mechanisms underlying these predisposing factors. For infectious diseases such as malaria and Legionnaires’ disease, genetic profiling with bacterial genomes provides insight into how these pathogens react to host defense mechanisms. The Complex Traits Group also collaborates with clinicians in order to help translate the findings from the lab to the clinic, and to ensure that the systems biology approaches employed reap benefits for human health.