Lorne special: Cell polarity and the T-cell

Sarah Russell

This feature appeared in the January/February 2010 issue of Australian Life Scientist. To subscribe to the magazine, go here.

Sarah Russell describes herself as a hard-core biologist of the signalling variety. She spent her early career doing straight biochemistry to get a handle on the signalling pathways that make lymphocytes - specifically T cells - do their stuff.

However, in recent years, Russell has seen the light. Literally. She now spends much of her time addressing the same core biological questions but through the lens of a microscope. And it’s certainly one of the best times in the history of microscopy to be just that, with new advances in fluorescence and laser capabilities for viewing and analysing cells appearing almost monthly.

The change in Russell’s experimental approach to T cell research really kicked off about a decade ago. After a highly successful postdoctoral stint at the National Institutes of Health (NIH) in the U.S. working on the pathways that control IL2-receptor signalling to mediate the immune response, she returned to Australia and started looking for different ways to further understand these immune signalling pathways and complexes.

“I had a fabulous time at the NIH, identifying players in the IL2-receptor complexes and so on. But at the end of my postdoc we had a large collection of proteins, and couldn’t really work out what was doing what. Then I realised that simply finding out what sticks together, from a biochemical viewpoint, was not enough to elucidate the signalling pathways.”

Once back in Australia, Russell became interested in the idea that cellular context and compartmentalisation were going to be defining factors in the control of signalling responses. In other words, she needed to find out exactly where, and with what other proteins, her proteins of interest reside in the cell at any given stage in the T cell’s many functions.

She also realised that microscopy was really the only way to look at the pathways and components that she needed in the context of cell compartments. One of the first technologies that piqued her interest for investigating the bank of candidate protein-protein interactions emerging from her biochemical and molecular biology data was Fluorescence Resonance Energy Transfer, or FRET microscopy. FRET gives information about whether two or more fluorescently labelled proteins that are close together in a cell might actually be interacting.

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