Do these genes make me look "fat?"

Dr. Christopher McMaster (Abriel Photo)

Fat isn't just something that hangs around your middle after the holidays. Up to 1,000 different fats, or lipids, are part of the body's complex signalling network, telling our cells what to do, and when to do it.

But sometimes, there's a problem in the network. When lipid metabolism goes wrong, it can lead to diseases like obesity, heart attack, stroke, and cancer. As Canada Research Chair in Biosignalling, Dr. Christopher McMaster is using genetic approaches to find new ways to counter lipid misregulation. The goal is to identify new targets which may lead to better treatment options for these types of diseases. His research is also contributing to the development of a new class of antibiotics, which could help fight drug-resistant bacteria.

"Lipid molecules are involved in almost every aspect of cell biology," says Dr. McMaster. "Lipids are stimulating molecules within and between cells. When a cell needs to "talk" to itself or to other cells, it will actually metabolize these lipids and send them as a signal to multiply the cell's function, such as to tell it to start or stop growing."

This involves identifying the genes that control lipid metabolism and their protein receptors. As Dr. McMaster points out, this is no easy task since many different genes are involved and they are influenced by environmental factors like diet and exercise. The ultimate goal is to use this research to develop more effective, targeted drugs and treatments for various human diseases.

Developing the first new class of antibiotics in 30 years is Dr. McMaster's second avenue of research. "It's the same underlying processes in developing an anti-cancer drug and an antimicrobial," he says. "Both avenues of research are based in lipid metabolism and how it regulates cell growth."

He explains that bacteria possess lipid metabolizing proteins completely different than those in our bodies, so the idea is to find a molecule that only binds to the bacteria's protein to prevent it from forming a cell membrane. Bacterial toxins, which may cause conditions like septic shock, are also a type of lipid, and he is searching for drugs that also prevent toxin release.

In collaboration with Dalhousie researchers Drs. David Byers and Donald Weaver, Dr. McMaster has established a Chemiinformatics Drug Discovery Laboratory at Halifax's IWK Health Centre, to research and develop this new antibiotic, thanks to nearly $4 million in support from the Canadian Foundation for Innovation.

Dr. McMaster joined Dalhousie's Atlantic Research Centre in 1996, and is Associate Professor in the Departments of Pediatrics and Biochemistry and Molecular Biology.