$17 million grant helps fight disease

November 17, 2005, vol. 34, no. 6
By Carol Thorbes

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Pathogenic microbes - bacteria and viruses that have the potential to wipe out huge numbers of people and animals by causing infectious diseases - have good reason to fear Fiona Brinkman.

The Simon Fraser University molecular biologist is a co-investigator on an international project that has been awarded $17 million dollars by Genome Canada and Genome B.C.

Brinkman will use $1 million of the funding for the Pathogenomics of Innate Immunity project (PI2) to fuel her crusade to improve treatments of infectious diseases. Building on knowledge gained in previous projects about how microbes mimic their hosts' gene functions to bypass their innate immune systems, Brinkman will create the world's first innate immune database.

PI2 brings together scientists in B.C., Saskatchewan, England, Singapore and Ireland to isolate how genes common to humans and animals can be modified to make innate immune systems more impenetrable to microbial pathogens. “The innate immune system provides the initial line of defence against an invading microbe,” explains Brinkman, the research director of bioinformatics on PI2.

“It makes sense to beef up that system's ability to shut out pathogens, rather than rely on antibiotics to kill pathogens after they have already gained a foothold in the body. Not only can pathogens mutate within their hosts to resist antibiotics, but also bacteria, such as Salmonella, produce toxins that antibiotics cannot destroy. In fact, killing some bacteria with an antibiotic can worsen disease symptoms, since more toxin is released from the bacteria when they are killed.”

Salmonella causes both non-typhoid salmonellosis and typhoid fever. Salmonellosis is one of the most common bacterial infections in North America, killing 600 people annually in the United States. There are 16 million cases of typhoid fever worldwide annually, resulting in 600,000 deaths.

That is why PI2 investigators are focused on seeing how genetic manipulation of the innate immune systems of humans and various animals improves their ability to lock out salmonella. Brinkman's project partners will conduct gene knockout experiments in labs to see how salmonella reacts to innate immune system genes being turned on and off. Brinkman will collect, cross-reference and analyse this data, ultimately creating a computational reference manual on how to build the most pathogenic microbe-resistant innate immune systems.

“If we can figure out which genes need to be turned on or off to boost our immune system function, without prompting that system to cause harmful inflammation, then we'll have won a major battle,” says Brinkman. Brinkman is a firm believer of a famous Chinese military strategist's theory: “Attack your enemy where he is unprepared.”

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