February 2, 2010

Research Leaving the Lab: Prof Models Tuberculosis

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Tuberculosis is believed to have been affecting humans since approximately 7000 BC. Most Americans do not worry about TB because of its rare occurrence and regular screening throughout the United States. However, almost a third of the world’s population is thought to be infected with the disease. Because it remains prevalent, Prof. David G. Russell, microbiology and immunology, devotes much of his research to TB.

In order to study TB progression, Russell and Mijeong Kim grad studied the lung tissue of TB patients from Capetown, South Africa. Kim examined tissue granulomas, or the ball-like collections of immune cells which form when the immune system attempts to eliminate foreign substances. Kim’s research indicated that the granulomas were in different developmental states thus making disease diagnosis and treatment problematic.

“The progression of the disease is decided at the granuloma. It is a local response. And that has many issues when it comes to management of disease because there is no systemic way of identifying the disease until the patient starts coughing TB all over everyone else,” Russell said.

In order to solve this problem, Russell and his team created a model of TB progression. Russell found an altered lipid metabolism in the granuloma tissue.

Russell’s findings indicate that tuberculosis forces macrophages to release lipids. According to his model, this lipid excretion is then internalized by bystander cells.

While Russell’s model could lead to earlier TB detection methods, he admits it is currently controversial.

Russell’s research also examines what predisposes HIV patients to infections like TB. While working with patients in Malawi, Russell made a puzzling discovery.

“We found multiple patients with poly-microbial respiratory infections even when their CD4 [T-cell] counts were pretty intact. [For] most people, when you talk about development of TB or onset of AIDS, it’s because of a loss of T-cell surveillance, but there might be an underlying problem here.”

In order to study this, Russell examined the superoxide burst of infected HIV-patients. A superoxide burst is the release of a reactive oxygen compound, a superoxide radical, by immune cells in the presence of bacteria, like Mycobacterium tuberculosis. The bursts degrade foreign bacteria.

In collaboration with colleagues, Russell used an assay to study superoxide bursts. An assay is a procedure in molecular biology for testing and measuring the activity of a biochemical in an organic sample. The assay examined the superoxide burst of infected patients. Russell learned that HIV suppresses the burst in macrophages.

Russell’s recent research looks at how TB reacts to environmental shifts.

To determine what environmental elements the “bug” does respond to, Russell and his research associates looked at the effects of pH on infected macrophage cells and on artificial test-tube environments. The pH was altered in all environments, but the results were inconclusive.

According to Russell, these results show that further experimentation on actual cells with other experimental elements is needed.

Russell expressed his hope to move most of his research from artificial situations to real life situations. “That’s where the title ‘From Patients to Plastic Beads’ comes from,’” he said. “It’s sort of moving from a very, very controlled and defined lab environment to the real disease.”

Original Author: Maria Minsker