MI4 Platforms

We carry ~2 kg of microbes (bacteria, fungi and viruses collectively referred to as microbiota) in and on our bodies that have potent effects on diseases ranging from diabetes and cancer to neurodegeneration. To understand the function of these complex microbial communities, the use of small animals, such as mice, raised under germ-free conditions (i.e. devoid of all microorganisms) offers a blank canvas onto which known communities of microbes (i.e. gnotobiotic) may be "painted” and studied. The MI4 gnotobiotic animal research platform will provide infrastructure, experimental consultation and training for any investigators in the McGill community and our collaborators interested in performing germ-free or gnotobiotic animal studies.

The human microbiome—the ecosystems of micro-organisms in us and on us—is a new frontier in health research. Mostly still unknown to science, these microbes permeate our skin, mouths, lungs, genitals, gastro-intestinal tracts and interact with our own cells for healthy body functioning. With your help, we are bringing together researchers from across the University and its hospitals to better understand the spectrum of beneficial and detrimental roles of the microbiome in health and disease, and to develop new and improved health care strategies.

The Infectious Disease Clinical Trials Unit will allow McGill University hospital sites to both lead and participate in exciting studies which define and refine our understanding of how to treat infectious diseases. The trials unit will help researchers and patients at the McGill University Health Centre and Jewish General Hospital achieve optimal care by both determining how we can make better use of the antibiotics we currently have and by providing access to new antibiotics for the hardest to treat infections. Paramount in these efforts will be the development of the strategies required for judicious and safe use. Leveraging the wealth of clinical excellence at our hospitals and the scientific wealth at our university, the MI4 Clinical Trials Unit will become an internationally recognized centre of excellence in the development of the most innovative and effective clinical treatments, research methodologies, and analytic approaches.

Imagine looking at a painting through a pinhole—it would be impossible to know what the full picture looked like. Now imagine looking at that same painting through 100 pinholes, and now the full picture starts to become clearer. Imaging mass cytometry (IMC) is a new, cutting-edge technology that finally gives researchers the ability to look at diseased tissues through many pinholes simultaneously, providing unprecedented knowledge that has the potential to lead to curative therapies for diseases ranging from neurodegenerative disorders, cystic fibrosis and cancer.

MI4 investigators studying infectious diseases work in the lab with microogranisms that make millions of people sick worldwide. To ensure that the people working with these bugs stay healthy, and that these organisms stay contained in the lab, MI4 supports the use of containment labs. By ensuring safe and secure handling of microbes, the level 3 containment lab allows investigators to directly study the microbes that are most likely to make people sick, with the view to developing new tests, treatments and vaccines to prevent these illnesses.

The challenges to design and develop successful drugs and therapies to treat diseases originates from the tremendously high complexity of the cellular heterogeneity of healthy and diseased tissues. To tackle these hurdles we have established our Flow Cytometry & Cell Sorting Platform (FCCSP) that allows the genetic, molecular and functional analysis of cells from preclinical and clinical samples with tremendous analytical depth. Thereby, our platform is essential to provide mechanistic insights that define health vs disease, to assess and develop biomarkers for diagnosis and tracking of disease progress vs regress, and to guide the development of personalized prophylactic and therapeutic treatment strategies to improve human health.

Animal models are often blamed for the high failure rate in the drug discovery pipeline, with promising results and small molecules in rodents often failing to replicate when brought to humans. Thus, to model and treat diseases linked to immunity and infectious agents, as researchers we should aim to work with a human system, closely resembling the areas affected in the disease itself. With this in mind, our platform proposes to generate three dimensional neuronal, lung, liver and GI organoids, to provide MI4 researchers with a unique, physiological human model to ask any number of questions with “human tissue on a dish”.

The human body consist of 37.2 trillion cells, an incredible number! In the past, we didn’t have the ability to study the behaviour of each of these cells, but now, new cutting edge Single cell genomic technologies open the way to study samples at unprecedented resolution, and address questions that have remained unanswered for years. This facility combines powerful, state of the art laboratory and computational tools that will allow the development of a better understanding of the immune system and new therapies to be developed for infectious diseases and autoimmune disorders.

Antibodies are molecules with the extraordinary property of honing and binding their targets very tightly, and are therefore indispensable to the diagnosis and therapy of infectious and immune diseases, and to basic and translational biomedical science in general. Here we propose a platform to barcode antibodies - using DNA as a programmable barcode – to allow us to quickly detect bound antibodies in blood and tissue and track multiple targets simultaneously. Our platform and barcoded antibodies will help map the complex molecular landscape that underlie health and disease, and will lead to biomarkers for early diagnosis of disease using a drop of blood, help track disease progression, and help guide personalized and precision therapeutic interventions.

Immune cells need to travel through the body to fight off infections. Several rare inherited immunodeficiency diseases in children are caused by defects in the movement of immune cells. Recent technological breakthroughs allow us to follow cells as they migrate through tissues and watch cellular motion involved in infections, cancers and inflammation. Our team has tremendous expertise in harnessing these new microscopy technologies. MI4 funding will allow us to further build our diverse interdisciplinary team to generate new data with state-of-the-art microscopy and computationally analyze these dynamic image data to fully exploit the information they contain. We will visualize and measure the immune system in action, scale up analysis using machine learning and Artificial Intelligence and learn how immune cells behave in normal and diseased states. The technology and expert team will be available to the broader community to improve the health of Canadians.

Mouse model studies are a cornerstone of understanding disease pathogenesis, the development of new drugs and vaccines, and regulatory compliance when drugs are brought to market. Building on 30 years of experience, our Genome Canada funded Infection & Inflammation core provides standardized functional and outcome analysis in mouse models of pathogen or immunogen challenges that mimic common infectious and inflammatory diseases (e.g. influenza, malaria, herpes virus infections, multiple sclerosis, inflammatory bowel disease). Support from MI4 will allow the Infection & Inflammation Phenotyping core to meet translational researchers’ growing needs for additional disease models (e.g. rheumatoid arthritis, lupus, scleroderma, asthma) and provide mice that are stably engrafted with a functional human immune system, making them ideal for efficacy and safety assessments and the study of human-specific pathogens.

Advances in genomics have opened the door to research on the role of human genetic variation in the population distribution, transmission, and severity of infectious diseases revealing genes and immune cell pathways associated with disease susceptibility. These discoveries offer enormous potential for the development of preventive and therapeutic strategies. Building on the McGill Regenerative Medicine network initiative and the support of our partner, Cryoviva (https://www.cryoviva.com/), the HSC-GP platform will (i) establish a reference panel of hematopoietic stem cells (HSCs) that capture genetic diversity throughout the world; (ii) provide the conditions to differentiate HSCs into immune cell types and to infect them with biocontainment level 2 microbes; and (iii) train the users for a genomic-driven analysis of the immune cell function (e.g. pathogen load, cytokine expression, transcriptional profiles) in response to pathogen challenge. The platform will bring novel genomic approaches to MI4 investigators interested in discovering basic cell mechanisms that underlie susceptibility to infection and can provide targets for intervention, markers of susceptibility and correlates of disease progression.