Medical researchers hunt for cells' production secrets

Brain gain researchers show the power of taking an interdisciplinary approach to medical research

by Hilary Thomson staff writer

Why does one blood cell spend its lifetime fighting infection while another concentrates on clotting?

Kelly McNagny and Sarah Townsend, two researchers at UBC's Biomedical Research Centre (BRC) are working together to find out.

They're collaborating on a study of the molecular mechanics of stem cells, the single precursor cell that produces the wide variety of mature cells found in blood, each with its own function.

"Knowing how to trigger the production of specific cells could allow us to correct the imbalances that result from diseases or even from toxic therapies such as chemotherapy," says Medical Genetics Asst. Prof. McNagny, who joined the BRCin 1998 from the European Molecular Biology Lab in Heidelberg, Germany.

Stem cells produce at least six types of cells: oxygen-carrying red blood cells; platelets that help blood coagulate; granulocytes that poison bacteria and parasites with toxic chemicals; macrophages that attack and consume infected cells; and T-cells and B-cells that help the body defend itself from infection.

Normal stem cells, also called progenitors, are rare--only one exists in 100,000 cells--and that makes them hard to find, track and study.

That's where immunologist Sarah Townsend comes in.

An expert in ultra-high sensitivity cell sorting recently recruited from California's Stanford University, she has founded UBC's Multi-user Flow Cytometry Facility at the BRC. It recently installed a cell sorter that can scan and analyse up to 25,000 cells per second. The instrument then picks out rare cells that have been tagged by a fluorescent marker and purifies them into a population that can be studied.

The cell sorter is a key part of the multi-user facility, which is used by biologists across campus in disciplines ranging from forestry to pathology. "This instrument is probably the best in Western Canada--it allows us to do cutting edge science here at UBC," says Townsend, an assistant professor of Medical Genetics. "With it, we can find an individual cell, see what it does, where it goes and what genes it expresses."

Townsend is helping McNagny examine MEP21, a molecule that he discovered which can be used as a new marker to sort stem cells.

MEP21 closely resembles another molecule called CD34 that has been used for more than a decade to identify human stem cells in bone marrow and blood. With McNagny's identification of MEP21, scientists now have two independent markers to help them track down stem cells.

In studying MEP21 for its use as a potential marker, McNagny has learned that it may serve as "molecular Teflon" that makes cells more mobile.

McNagny's lab has found that a strain of mice with mutations in the MEP21 gene have a birth defect where tissues of the intestine stick too tightly to the abdominal wall.

This closely resembles a life-threatening birth defect that affects one in 6,000 human babies and McNagny's work may provide insights into new therapies for treating this defect. The protein may also be useful in treating thrombosis where cells are overly sticky and bind to form blood clots.

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