Tuberculosis

Because tuberculosis manipulates host cells to resist the immune response and current drug therapies, Nigel Savage of Leiden University Medical Center in the Netherlands will utilize RNAi analysis to identify the essential pathways used by the bacteria to modify its host cell. By discovering these pathways, novel therapies can be developed to counteract this host manipulation without directly targeting the pathogen and causing the development of resistance.

Dan Feldheim of the University of Colorado in the U.S. will test his hypothesis that gold nanocrystals coated with drug compounds can effectively inhibit protein- protein interactions that often drive disease pathogenesis, will be less susceptible to evolutionary mechanisms that lead to drug resistance, and offer enhanced drug delivery characteristics. This project's Phase I research demonstrated that gold nanocrystals can be tailored to circumvent many viral and bacterial evolutionary drug resistance mechanisms.

Samantha Sampson of Imperial College London proposes introducing short strands of modified DNA into tuberculosis cells for direct and highly specific targeting of DNA sequences. If successful, it will effectively "lock" DNA, obstruct replication and transcription, and prevent bacterial growth and survival.

Anwar Jardine of the University of Cape Town in South Africa will attempt to disrupt the biosynthetic pathway of mycothiol, which is produced by the tuberculosis bacterium as a protective chemical compound. By targeting this metabolic pathway specific to mycobacteria, Jardine hopes to eliminate latent tuberculosis or make it more vulnerable to existing drugs.

Shaorong Chong of New England Biolabs in the U.S. will synthetically reconstruct essential biological processes of Mycobacterium tuberculosis and use this system as a drug-testing platform for the screening of small-molecule therapeutics against multi-drug resistant M. tuberculosis.

Robert Abramovitch of Michigan State University in the U.S. will use their high-throughput drug discovery platform to identify new drugs for treating chronic tuberculosis and for potentially shortening the current treatment time of six to nine months. Their platform exploits a genetic region known as the DosR regulon thought to underlie the behavior of the causative bacteria in humans under low oxygen conditions, when they become dormant and thereby resistant to current drugs.

Erdogan Gulari of the University of Michigan in the U.S proposes to design and produce a large library of antimicrobial peptides (AMPS) that will be tested against Mycobacterium tuberculosis strains to identify potential new drugs that can damage the bacterial membrane and be less susceptible to evasion by the development of resistance.

Ines Atmosukarto of Lipotek Pty Ltd. in Australia proposes to develop a novel TB vaccine utilizing synthetic "nano-sacs" called liposomes that carry TB antigens and are anchored with a self-adjuvanting protein that binds to and stimulates dendritic cells.

Jeff Schorey of the University of Notre Dame in the U.S. will evaluate the use of exosomes, which are small membrane vesicles released from macrophages infected with Mycobacterium tuberculosis, as a new platform for TB vaccines. Exosomes contain proteins and glycolipids that can elicit a robust innate and acquired immune response.

Gyanu Lamichhane of Johns Hopkins University in the U.S. will develop a novel vaccine for TB based on existing BCG vaccines modified to express a gene that is specific to latent TB in order to generate a robust immune response to a latent infection.