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Professor Makes New Strides in Blocking Intestinal Infection

Steven Singer  “While both humans and mice produce a strong antibody response during infections with Giardia, we have found that these antibodies –unlike certain other cell responses – are not necessarily required to control acute infections with this parasite," said Steven Singer, co-director of Georgetown's Center for Infectious Disease.

November 6, 2013 – A Georgetown professor has made another step toward eradicating Giardia, the leading parasitic cause of diarrhea in humans in the United States and around the world.

Biology department chair Steven Singer, who also co-directs Georgetown’s Center for Infectious Disease, has been studying Giardia for 17 years.

His lab was the first to successfully manipulate the parasite genetically, and his research team also has demonstrated that antibodies are not required to control the infection, and that intestinal neurons play an important role in parasite elimination.

Fighting the Infection

“The research area in my lab focuses on the host's immune response to the parasite,” Singer says. “While both humans and mice produce a strong antibody response during infections with Giardia, we have found that these antibodies –unlike certain other cell responses – are not necessarily required to control acute infections with this parasite.”

In a study published today in the online journal mBio, Singer and his research team examined the effect of the intestinal parasite Giardia duodenalis on different genes in mice.

The products of one particular gene – called Mmp7 – can kill Giardia in a test tube, but removal of the gene has only a minor effect on mice that have contracted the infection. Another gene – Nos2 – that produces nitric oxide has been shown to inhibit parasites in culture, but also has little effect in live animals.

The researchers bred mice lacking both genes and found that they were much more susceptible to infection than the mice lacking either one of them.

Redundant Genes

“This is a rare concrete example of the redundancy of our immune system, showing exactly which genes are redundant and can therefore work together to fight an infection,” he says. “Our findings suggest that the function of these genes are redundant – either one couldhelp eradicate the infection, so while blocking either one had little effect, blocking both was much more dramatic.”

He says that the idea that immune systems are highly redundant is not new – but the study revealed one of only a few examples in which this phenomenon is clearly demonstrated.

“This research brings us one step closer to understanding the best mechanisms to control this pervasive infection,” says Singer.

Multiple Weapons

“The immune system has multiple weapons which it uses to help control infections,” Singer writes in the study. “Many infections result in activation of several of these response mechanisms, but it is not always clear which responses actually contribute to control of the pathogen and which are bystander effects.”

Also an adjunct associate professor at Georgetown’s Lombardi Comprehensive Cancer Center and in the Department of Microbiology and Immunology, Singer worked on the research with Erqui Li, associate research professor of biology, Ernest Tako (G’08) and Maryam Farzad Hassimi (G’01), now of the Sloan-Kettering Institute.

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