Jay Solnick of the University of California, Davis will explore whether the bacteria Helicobacter pylori, which can cause peptic ulcers in some people, might enhance immunity to tuberculosis and help maintain tuberculosis in a latent state.
Carl Nathan, Julien Vaubourgeix and Gang Lin of Weill Cornell Medical College will test their hypothesis that tuberculosis is able to exit latency by distributing damaged proteins to a senescent cell lineage, while more functional proteins are diverted to a lineage with full replication potential. Regulating this post-latency cell division could be the target of new drugs. This project's Phase I research demonstrated that M. tuberculosis accumulates irreversibly oxidized proteins when its replication is blocked. These proteins form small aggregates that fuse into larger ones.
In an attempt to capture and study latent tuberculosis cells, which are reservoirs of infection and highly resistant to treatment, Kim Lewis of Northeastern University will pulse-label tuberculosis cells with green fluorescent protein. While active cells divide and dilute the GFP, latent cells, which are dormant, will remain bright green, allowing for their observation and tracking.
Because cystic fibrosis patients and carriers appear to be resistant to tuberculosis, Jerry Nick of National Jewish Medical and Research Center in the U.S. will study whether mutations of the CFTR gene, which causes the disease, reduce or eliminate latent TB infection.
Pulmonary macrophages are the principal host of tuberculosis, where it can remain latent and inaccessible to current TB drug therapies. Dmitry Shayakhmetov of the University of Washington will study whether infecting these host cells with adenovirus will induce rapid cell death, reducing TB load and blocking the re-infection cycle.
Matyas Sandor of the University of Wisconsin will graft granulomas, nodules that form as a result of long-term inflammation, to study the role they play in TB latency and reactivation.
Sarah Fortune of Harvard University will research whether chromatin crystallization, in which DNA condenses into a protective matrix due to environmental stress, occurs in tuberculosis and is a characteristic of latent organisms.
Axel Heiser of AgResearch Ltd. in New Zealand proposes to develop a new type of tuberculosis vaccine that uses polyester biobeads produced in mycobacteria that carry a large repertoire of known and undiscovered antigens on their surface. This new technology combines the multiple antigenic benefits of live vaccines with a better safety profile and lower costs of production.
Jeffrey Withey of Wayne State University in the U.S. will test whether oral consumption of the unsaturated fatty acid linoleic acid could be used as a simple low-cost therapeutic to block the production of cholera toxin by the bacterium V. cholerae, which causes diarrhea. Linoleic acid could be used as a preventative therapy or as a supplement to the standard treatment of oral rehydration solution to improve recovery time for cholera patients.
Manu Prakash and a team at Stanford University in the U.S. will field test their origami-based paper microscopes designed for disease diagnostics. These lightweight print-and-fold "Foldscopes" can be packed in a flat configuration, assembled in minutes, have no mechanical moving parts, and can be incinerated if required. Testing the device in India, Thailand, and Uganda will allow user feedback to help refine the design for future scale-up.