Overview of Research at the Centre

The Manitoba Centre for Proteomics and Systems Biology was established to use new methods to study questions of biological and medical relevance. The approach has been to consolidate expertise in several areas of basic and clinical research at one site to encourage interaction, discussion and collaboration. The Centre is also intended to function as a resource for the research community of Manitoba offering intellectual and technical expertise on a collaborative basis.

Immunology & Cell Biology

Immune cells migrate in the body and enter infected and inflamed tissues during infection and inflammatory diseases. In cancer, tumor cells can migrate and invade other tissues resulting in the disruption of normal tissue architecture and function. Studies using proteomic and microscopic methods are aimed at defining the mechanisms controlling cell adhesion in a number of key cell types. The aim is to understand how these events work and to identify ways of selectively interfering with them. This could be of significance in autoimmunity, transplantation, cancer and viral infections.

In conjunction with our colleagues in the Arthritis Research Centre, we are examining the autoantibodies present in the joints of patients with arthritis. This is achieved using proteomic methods (mass spectrometry, biochemistry) to identify the autoantibody reactivity. The goal is to define what the autoantigens are in these patients and to determine if these can be used to identify at risk individuals before disease develops. This may provide a basis for understanding how the disease starts and what may be targets for early intervention.

Virology

Virology research examines the mechanisms by which a virus can, or cannot, cause disease in an organism. Infectious diseases account for 15-20 million deaths and tens of billions of dollars worth of societal costs per year. The vast majority of such infections are caused by viruses, and those viruses with RNA genomes account for more than ? of disease and economic loss. This lab uses assembly-defective temperature-sensitive virus mutants, and applies genetic, molecular biologic, biophysical, and Proteomic analyses to understand how the model virus "reovirus" infects cells, causes pathology, and assembles. Other research interests involve understanding how certain viruses can cause disease in some cells but not in others (for example, West Nile virus kills animal cells but has little, if any, effect upon insect cells).

The new infrastructure within the MCPSB will allow more complete and systematic analysis of how particular viruses affect the various cells they grow in. This will provide clues about how cell and tissue damage are caused by viruses, which in turn can be used to find the underlying mechanisms whereby viruses cause disease. This is hoped to lead directly to better fundamental understanding of complex cellular events as well as better chemotherapeutic strategies to greatly reduce virus-associated morbidity and mortality.

Rheumatic Diseases

The rheumatic diseases research program undertakes projects related to the pathogenesis, prognosis, and treatment of rheumatic diseases. Currently, the following questions are being addressed in funded research projects: 1. What are the biological mechanisms in the inflamed joints of rheumatoid arthritis (RA) patients that contribute to the persistence of the inflammation and its lack of resolution; 2. Can the onset of RA be predicted in high risk Aboriginal populations using combinations of antibody, genetic, and proteomic testing; and 3. Can the response to treatment of patients in the early stages of RA be predicted using proteomic and genomic approaches?

Addressing these questions involves a coordinated approach between basic scientists, clinical scientists, and epidemiologists. The scientists in the Rheumatic Diseases Research Lab work closely with the clinician scientists in the University of Manitoba Arthritis Centre in analyzing biological samples and relating this data to data generated from the patients' clinical course.

Transplantation

The Winnipeg Adult Renal Transplant Group has as its goal to discover the immune mediators of kidney transplant rejection and how to improve survival of the transplants and the overall lives of our patients. For example researchers are using state-of-the-art proteomic research tools to identify unique proteins involved in kidney rejection. Recognized for their ground breaking work in this area, the Winnipeg Transplant Group was the only Canadian centre recruited as a member, to act as the core proteomic and pathology labs for a multi-centre NIH (US National Institutes of Health) sponsored clinical trials group involving the Cleveland Clinic, Emory and Yale Universities. Once these proteins are fully characterized and identified this body of work will provide the pharmaceutical industry with novel targets in the design of new immunosuppressive therapies to prevent and treat transplant rejection and thereby improve the lives of patients with kidney disease.

Models of Genetic Diseases

The Manitoba Institute of Cell Biology (MICB), a joint institute of the University of Manitoba and CancerCare Manitoba, is co-leading the Canadian component of "The International Knockout Mouse Project", a major international genomics research project aimed at better understanding human genetic diseases. Researchers are working with other scientists from around the world to create a library of genetic mutations in mouse cells — a powerful research tool with immense possibilities in furthering research on cancer and hereditary diseases, as well as the pursuit of new treatments.

Physiology

There are two areas of physiological and clinical importance open to a systems biology approach. These are the molecular regulation of the human growth hormone gene family, as well as the growth factor (FGF) and FGF receptor axis in the context of heart muscle growth and response to injury.

Cardiology

Current research projects include examining the role of heart cells and how it controls the cell survival and growth.

Cancer

Research interests include understanding the mechanisms regulating gene expression in normal and cancer cells. They are also researching biomarkers in early detection of breast cancer and biomarkers in the detection of life-threatening forms of prostate cancer.

Models of Genetic Diseases

The Manitoba Institute of Cell Biology (MICB), a joint institute of the University of Manitoba and CancerCare Manitoba, is co-leading the Canadian component of "The International Knockout Mouse Project", a major international genomics research project aimed at better understanding human genetic diseases. Researchers are working with other scientists from around the world to create a library of genetic mutations in mouse cells — a powerful research tool with immense possibilities in furthering research on cancer and hereditary diseases, as well as the pursuit of new treatments.

Instrument & Separation Development

This group develops improved methods of mass spectrometry for applications in the biological sciences. They are active in studying fundamental processes in ion production from biological material, and in development of instrumentation related to time-of-flight mass spectrometry, some of which has been successfully commercialized. Recent efforts are directed toward mass-selected imaging of biological tissue.

Biological systems are highly complex mixtures containing 100s of thousands of different types of molecules. The challenge is to separate these so that they can be identified and characterized. A major research area in the Centre is to develop new approaches that interface with mass spectrometry to increase these capabilities.