Grand Challenges Explorations projects receive new grants for tuberculosis research

Nov 10 2010

Weill Cornell Medical College announced today that it was awarded two $100,000 grants from the Bill & Melinda Gates Foundation as part of the next phase of Grand Challenges Explorations, an initiative to encourage bold and unconventional ideas for global health. The grants will provide continued support to promising and innovative global health research projects conducted by Dr. Carl Nathan, titled "Senescent and Rejuvenated Mtb Subsets on Exit From Latency," and Dr. Kyu Rhee, titled "Metabolosomes: The Organizing Principle of TB Latency."

Dr. Nathan's and Dr. Rhee's projects are two of nine grants to receive new funding. In 2008 and 2009 respectively, Dr. Nathan and Dr. Rhee received initial $100,000 grants under Grand Challenges Explorations. These new awards represent "next stage" funding for Grand Challenges Explorations grants that have shown progress in their initial grant period and that align with the Gates Foundation's strategic priorities.

"The Grand Challenges Explorations projects receiving this new funding have been scientifically successful in their initial research and show great potential," says Dr. Tachi Yamada, president of the Gates Foundation's Global Health Program. "Our hope is that one day these projects will lead to breakthroughs that could save millions of lives in developing countries."

Targeting TB as It Emerges From Latency

Dr. Nathan and his lab will study the genetic mechanism by which tuberculosis emerges from its latent state into an infectious and symptomatic disease. Specifically, they are testing the idea that tuberculosis exits dormancy by dividing asymmetrically, so that one progeny cell inherits most of the oxidatively damaged proteins and the other is spared. Blocking this process could aid treatment.

Tuberculosis is a major cause of death around the world, with as many as one-third of the world's population infected with the bacterium, among whom about 8 million develop the disease each year and more than 1.6 million succumb, mainly in developing countries. The majority of those infected have a clinically latent infection; that is, they test positive for the bacterium but are asymptomatic and not contagious. However, 5 percent to 10 percent of this latent group will develop tuberculosis, becoming symptomatic and infectious.

"Understanding how the mycobacterium resumes replication will be key to reducing the prevalence of latent infection to break the cycle of TB transmission," says Dr. Nathan, who is chairman of the Department of Microbiology and Immunology, the R.A. Rees Pritchett Professor of Microbiology, and director of the Abby and Howard P. Milstein Program in Chemical Biology of Infectious Disease at Weill Cornell Medical College.

Looking at Metabolic Basis of Latency in Mycobacterium Tuberculosis

Dr. Kyu Rhee and colleagues are testing the theory that Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, utilizes specific protein-based structures called metabolosomes to enter into, maintain and exit from latency.

According to Dr. Rhee, a major challenge to control of the TB pandemic is the lack of effective therapies against non- or slowly replicating forms of Mtb. Such variants are currently thought to represent the major form of Mtb found in latent TB infection. Latent Mtb is thought to represent the principal barrier to faster and more effective TB cures. Current TB treatments are longer than those for virtually any other bacterial infection and associated with significant rates of treatment default, failure and the emergence of drug resistance itself.

"Understanding how metabolosomes work may thus lead to new therapies that would help achieve control of the pandemic and potentially lead to its eradication," says Dr. Rhee, assistant professor of medicine in the Division of Infectious Diseases in the Department of Medicine, assistant professor of microbiology & immunology, and the William Randolph Hearst Foundation Clinical Scholar in Microbiology & Infectious Diseases at Weill Cornell Medical College.

Source: New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College