Therapeutics/Drugs

In an effort to enhance pathogen vulnerability to existing antibiotics, Angharad Davies of Swansea University in the U.K. proposes using peptides which activate stationary-phase microbes, leading to cell growth, with the aim of increasing susceptibility to established treatments.

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.

The bacteria Bdellovibrio -- harmless to humans -- naturally kill a wide range of gram-negative pathogens which are known to cause many infections. Professor Liz Sockett of the University of Nottingham in England will study whether these pathogens have the ability to form resistance to Bdellovibrio, and if Bdellovibrio can be delivered to patients as a living antibiotic.

Graham Rook of University College London will target an essential bacterial nutrient transport system with an iron-binding nanoparticle. The particle will be designed not only to block the pore and prevent it from taking in needed nutrients, but to also carry antibiotics that can be released in the vicinity of the bacterium.

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.

Carmenza Spadafora of Panama's Institute of Advanced Scientific Investigations and High Technology Services and José A. Stoute of Pennsylvania State University College of Medicine in the U.S. investigated whether malaria can be treated by microwave irradiation, an idea based on the unique electromagnetic properties of hemozoin, a metabolite formed by Plasmodium parasites in infected red blood cells. This project's Phase I research demonstrated that malaria parasites inside red blood cells are sensitive to low doses of microwaves that do not harm uninfected red blood cells.

To fight emergence of drug and vaccine resistance in rapidly evolving parasites, Pradipsinh K. Rathod of the University of Washington in the U.S. will identify the parts of the malaria genome which contribute to rapid increases in mutations, and will screen for small molecules that inhibit these mechanisms. This project's Phase I research demonstrated that hypermutagenesis does play a strong role in the development of drug resistance.

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.

Christina Smolke of Stanford University in the U.S. will develop synthetic biology platforms to improve the scale and efficiency of microbial systems used to discover, develop, and produce drugs based on natural products. Such new biosynthesis approaches could lead to new and less expensive drugs for global health.

Andreas Matouschek and Keith Tyo of Northwestern University in the U.S. will develop synthetic compounds that target essential proteins in the Plasmodium parasite for destruction by its own protein degradation mechanisms. This strategy could aid new small molecule drug development efforts to combat malaria.