Quantum Dots Light the Way

$400K study will zoom in closer on cancer cells

Three researchers from diverse fields have joined forces to develop a next-generation “microscope” for better understanding the important roles that proteins play in diseases such as cancer.

The study’s goal is to develop a new method for obtaining a clearer view of a cell and how the even smaller proteins within a cell behave and interact with one another. “This information is crucial to understanding the fundamental aspects of diseases like cancer,” says University of Calgary (U of C) chemist Dr. David Cramb, who is working on the project with U of C cancer biologist Dr. Susan Lees-Miller and University of Toronto quantum dots expert Dr. Greg Scholes.

The trio’s innovative project is fuelled by a four-year $400,000 grant from NSERC, Canada’s Natural Sciences and Engineering Research Council. The funding is part of NSERC’s Accelerator Grants for Exceptional New Opportunities (AGENO) initiative, which supports researchers with outstanding new ideas that have the potential for major breakthroughs.

“Solving the big problems in our world, like those in the field of medicine, absolutely requires a collaborative approach,” says Cramb. “It’s heartening to see that funding agencies recognize this and enhance the potential success of a new type of project like this.”

Specifically, the research team is developing a new technology – called fluorescence cross-correlation spectroscopy (or XCS) – to allow the simultaneous observation of three different types of proteins within a cell. Current methods only allow researchers to see a single type of protein in its native environment.

“One of the long-term goals of the study is that we hope the new technology will contribute to the diagnosis and treatment of disease on an individual basis,” says Cramb. For example, a potential application of XCS would allow oncologists to test various treatments or drugs on tissue samples from individual cancer patients. With a better view of protein activity, the oncologists could identify and personalize the most effective treatment for each cancer patient. “If the oncologist wanted to stop certain proteins from coming together, this would be a technology that could help them do that,” says Cramb. “They can test the drug of choice and see the results.”

Overall, XCS would provide a boon to the study of proteomics (the study of proteins within a cell). For example, Lees-Miller, the Engineered Air Chair in Cancer Research, is studying how cells recognize and repair radiation-damaged DNA. This type of DNA damage is not repaired by a single protein. “In these types of processes there are likely multiple proteins that come into play. So, one of the current challenges is observing this complex process happening in a live cell in real time,” says Cramb, adding that current imaging methods, such as electron microscopy or fluorescent microscopy, simply can’t do this job well enough.

The team’s new idea for studying proteins was hatched, in part, by the emerging use of quantum dots in the biological sciences. These nanoscale particles can “light up” biological entities in a range of sharp colours. Made from semiconductor materials, quantum dots are more durable, visible and easily manipulated than the chemical-based dyes that are currently being used. In fact, one of the world’s premier scientific journals, Science, named the quantum dot bio-imaging technology as one of the top 10 scientific breakthroughs in 2003.

“Our novel approach is to tag the proteins of interest with fluorescent quantum dots and use XCS to monitor the interactions between the proteins, since XCS provides a signal only when the proteins are connected to each other,” says Cramb.

The international pharmaceutical company AstraZeneca sees potential in the new technology and is currently funding a parallel study in the Cramb lab.