Two UTHCT scientists receive NIH grants to fund their research into tuberculosis

Thursday, April 13, 2006

Two Tyler scientists investigating distinct approaches to combating tuberculosis recently received two years of funding for their research from the National Institutes of Health.

Malini Rajagopalan, Ph.D., an associate professor of biochemistry at The University of Texas Health Science Center at Tyler, received $378,000 to study how tuberculosis bacteria multiply and spread inside the body. Amir Shams, Ph.D., an assistant professor of microbiology and immunology, received $368,000 to continue his research into a DNA-based TB vaccine.

Tuberculosis kills about 2 million people worldwide each year, according to the World Health Organization. About one third of the world’s population is infected with tuberculosis. TB is the second most common cause of death in the world resulting from infectious disease. It is caused by a bacterium called Mycobacterium tuberculosis.

Dr. Rajagopalan is examining a specific pair of genes in the TB bacterium called MtrAB. Genes are the building blocks of inheritance; they contain the instructions to produce a particular protein. MtrAB is the only essential gene pair out of all 11 regulatory gene pairs in the TB bacterium, she said. Dr. Rajagopalan and her research team want to know if this gene pair controls the multiplication of the TB bacterium.

“When we say it’s essential, we mean it’s needed for the TB bacterium to survive. We cannot remove this gene from the bacteria,” Dr. Rajagopalan said.

However, she and her team discovered that if they increased the number of copies of the gene, the TB bacteria inside the host organism quit reproducing.

“Because of the unique growth characteristics of the MtrA strain in macrophages – immune cells that act as scavengers and engulf foreign substances such as bacteria – and mice lungs, we think our MtrA strain has the potential to be part of a vaccine,” Dr. Rajagopalan said. MtrA makes up one-half of the gene pair.

TB bacteria need the MtrA gene to survive, making it a logical target for drugs designed to interfere with its functions, she said.

“We know tuberculosis bacteria can stay latent for extended periods of time and then revive when conditions become favorable. Does this gene have a role in modulating the multiplication of the TB bacterium?” Dr. Rajagopalan said. That’s the question she and her group want to investigate.

Dr. Shams and his research team are investigating peptides, short fragments of protein, from M. tuberculosis. These peptides are recognized by the immune systems of most people with latent tuberculosis. People with latent TB have efficient immune systems, do not have symptoms of the disease, and don’t infect other people.

The immune systems of people with latent TB effectively contain the infection, and they also respond very well to these peptides. Hence, these peptides could be good candidates for a new TB vaccine, Dr. Shams said.

“We wanted to look at how these peptides can induce protection against infection with M. tuberculosis,” he said. These “promiscuous” peptides are recognized by most people’s immune systems, and therefore they have strong potential for inclusion in a new TB vaccine.

“We are formulating a DNA vaccine that expresses these short peptides. We don’t know how protective they will be. Previous experiments with TB vaccine candidates worldwide have not generated optimal results. We expect that this DNA vaccine will be one of the first that does,” Dr. Shams said.

It’s likely that the results of his research will be applied to more than the development of an effective tuberculosis vaccine.

“It also will advance our knowledge of the peptide vaccines for infectious disease in general and for pulmonary diseases in particular,” Dr. Shams said.

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