Project Leader: 
Megan Levings

Lead Institution: 
University of British Columbia
 
Research Funding Program:
SOF 3  

"Tweaking the immune system to treat immune-mediated diseases"

The human immune system is highly responsive, yet tightly controlled; it must be able to respond appropriately to new threats like infections and viruses, but at the same time must not over react and attack the host. Immune responses are normally controlled by T regulatory cells (Tregs). Studies have shown that when Tregs malfunction or when their numbers change, the immune response is impaired; either the immune system doesn't respond appropriately when confronted with infectious disease or else it over responds, and attacks itself leading to autoimmune disorders such as type 1 diabetes.
 
Dr. Megan Levings at UBC, in collaboration with Nicholas Haining from the Dana Farber Cancer Institute and Ciraco Piccirillo from McGill University, hypothesize that if they can identify which Treg genes are  involved in the immune response, they may be able to find ways to tune the immune response up or down in individual patients. They will use the information about the Treg genes to create a screening tool, called a GE-HTS (gene expression-based high-throughput screening) platform, which they will use to test compounds to see if they can activate or deactivate Treg genes.

The challenge of this research is in first identifying and separating the Treg cells from other cells in the immune system. To do this they will obtain blood samples from healthy volunteers, and sort the blood cells using "Fluorescent Activated Cell Sorting," a well-developed technique that identifies, sorts and separates specific types of human blood cells, to obtain purified Treg cells. They will then separate the Treg cells into two groups and will activate only one group. By analysing and comparing the data, they hope to identify genes that are expressed only in the activated Treg cells. They will then fine-tune their results, by comparing their data to other published data, and the most important genes will be used to create a tool for identifying potential therapeutics.

At the end of this project the research team will have knowledge of which genes are important for the activity of Treg cells, and they will have the technology to test a large number of compounds to identify those that are able to influence Treg activity. This may lead to a powerful approach to treating disease; instead of developing many new drugs that target each disease, this approach may yield a few drugs that can be used to treat many different diseases, by tweaking a patient's own immune response as necessary.