Immunity and Infection Research Centre

2003 Research Unit Award

This unit’s overall mission is to advance understanding of the human immune response involved in transplantation and mitigation of infectious diseases. The unit brings together a multidisciplinary team of basic scientists, clinicians and health professionals who are undertaking basic and translational research involving molecular and cellular mechanisms of immunity. Their goal: to improve transplantation outcomes and the ability to understand and deal effectively with infectious diseases.

The health of an individual — and of a population — is critically dependent on the capability of the immune system to protect against disease. The immune system has evolved to protect against both new and variant pathogens (viruses, bacteria, parasites). However, pathogens also evolve and develop new ways of evading immune system defenses. Besides reacting to pathogens, the immune system also recognizes abnormal or foreign tissues as threats. Whether it is a cancer tumour or islet cells implanted for treatment of diabetes or a transplanted heart, the immune system is programmed to reject the foreign tissue. Since the underlying mechanisms of the immune response to pathogens or transplanted tissue are the same, infectious disease research and transplantation immunological research intersect and inform one another significantly.

This unit’s transplant immunology sub-theme addresses two key obstacles to effective transplantation: rejection of the graft (transplant) and side effects caused by immunosuppressive drugs required to limit the rejection response. At present, the status of graft tissue is monitored by clinical signs. Typically, however, the graft will already be damaged by the immune response before such symptoms are detected. Unit researchers will explore gene expression profiling as a mechanism for predicting the onset of rejection. They will also focus on better understanding molecular mechanisms that regulate immune cell function to help address the pressing need for better, more specific immunosuppressive drugs and drug regimens. By targeting the action of specific immune cells or processes rather than suppressing immune function generally, such drugs would counter rejection with less compromise to the patient’s immune system.

The infectious disease cohort at the Immunity and Infection Research Centre is focused on understanding mechanisms that enable certain pathogens, such as salmonella and TB, to infect and multiply inside immune cells — a remarkable phenomenon since these cells are programmed to ingest and destroy infectious agents. The centre’s research and other studies show that pathogens have the ability to disrupt key regulatory networks required for normal immune function. The goal is to develop new information about the molecular mechanisms that enable these infectious organisms to avoid destruction, and to apply the findings in the development of targeted therapeutics and vaccines. Studies will address:

• Interactions between proteins produced by pathogens, to understand the mechanisms pathogens employ to specifically target and manipulate regulatory enzymes within host cells.
• How protein networks are organized within microbial cells to confer viability and determine behaviour (e.g. virulence).
• How an immune response is activated, maintained and halted, in order to better understand how pathogens may simultaneously activate and repress different aspects of the immune system.

Completed award term September 2009.

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