Immunologist Professor Frank Griffin is excited about his research group's latest work - identifying and mapping genes that contribute to resistance and susceptibility to infection, using deer as an experimental model.

This could have applications to human health, potentially leading to genetic tests and other interventions for infectious diseases, such as malaria and tuberculosis, that kill millions worldwide every year.

Griffin, who heads the Disease Research Laboratory (DRL), based in the University's Department of Microbiology and Immunology, has been studying deer genes since the mid 1990s, in collaboration with Colin Mackintosh at AgResearch, Invermay.

He says deer are a "wonderful" model for studying infection because they show extremes of resistance and susceptibility, are very sensitive to the environment and produce a distinct immune response.

Much of the DRL's work has focused on combating tuberculosis (TB) and Johne's disease (a wasting disease that affects the gut) in deer.

Griffin says when his group began this work they noticed subgroups of deer were particularly resistant or susceptible to infection. "So we developed experimental models that allowed us to study infection with great precision, by infecting them with a small dose of bacteria, to see how infection became established. This allowed us to separate them into different groups, some inordinately susceptible or resistant."

Further experiments crossing highly resistant or susceptible stags with uninfected females found these traits were heritable - the genes were passed on to their offspring. Subsequent work identified naturally-occurring breed lines there that were susceptible and resistant.

Having established that there is a strong genetic component to resistance and susceptibility, the DRL team is now looking at "unbundling" the genes involved.

Griffin says we're living at a time when modern medicine has "arrested" natural selection by preventing babies from dying from infections that were once fatal. This effectively means a lot more susceptibility genes are present in the human population than there used to be.

If we can map genes contributing to resistance, and measure the effect of the environment and how these genes function, we can develop a preventive approach to managing disease.

Add the coming of HIV/AIDS, and the damaging effects of malnutrition and stressful lifestyles on our immune systems, and there are more immunecompromised people today than there were people 100 years ago.

The upshot is that we need to get smarter and better in finding ways to protect people who are susceptible.

"So we need to understand the genes that contribute to protection and resistance. We can't do this in humans because we obviously can't infect them [with bacteria], whereas with animals we have a model to study infection from day one - how disease develops, how we can prevent or reverse it. That's the really exciting thing."

Griffin says if we can map genes contributing to resistance, and measure the effect of the environment and how these genes function, we can develop a preventive approach to managing disease.

He envisages a time when a simple blood test will show whether a person is resistant or susceptible to TB, malaria, or viral infections such as hepatitis and HIV/AIDS. Susceptible individuals could then be vaccinated to boost their immunity or, with malaria, encouraged to take anti-malarial tablets when visiting affected countries.

Griffin's group is currently looking at up to 50 candidate genes to see which combinations give "true resistance" or make individuals susceptible. The next step is to refine them down to a small number that gives them the answers they want.

He expects five or six genes will be involved because the immune system relies on combinations of genes, rather than a single one, to prevent system failure.

Funding