Robert Dunn and colleagues at the University of Kansas in the U.S. will develop a diagnostic tool for the early detection of disease that employs writable compact discs that can be read in conventional computer disc drives. Microfluidic structures and immobilized antibodies will be fabricated onto small sections of a compact disc, along with enzymes that produce a reflective “silvering” surface upon recognition of target biomarkers. These changes in reflection can be read by any conventional CD drive, allowing for diagnosis using laptops in low resource settings.

Filippo Mancia of Columbia University in the U.S. will perform crystallization experiments on a key olfactory receptor used by mosquitoes to detect humans. The aim of these studies is to determine at an atomic level the conserved regions on the olfactory receptor in order to develop drug therapies to block these receptors. This project's Phase I research generated diffraction quality crystals of this targeted mosquito olfactory receptor, and in Phase II, the team will optimize the crystal to determine the structure of the receptor and how it binds to small molecule anti-malarial compounds. Visualizing this interaction in atomic detail will aid in the optimization of these compounds as highly effective insect repellents.

Roozbeh Ghaffari, Patrick Beattie, Jason Rolland, and Jeff Carbeck of Diagnostics For All & MC10 Inc. in the U.S. sought to develop disposable paper-based diagnostics devices embedded with optoelectronics, allowing quantitative colorimetric analysis for HIV viral load monitoring. This platform addresses practical limitations of current image capture methodologies and eliminates the need for external readers. In Phase I, they built a point-of-care detection device by incorporating ultrathin, flexible electronics onto a paper substrate, and tested its ability to quantify viral load by measuring levels of HIV p24 antigen. Having improved the sensitivity of their colorimetric assay, in Phase II Christina Swanson and her team will develop and test a new class of multiplexed, paper-microfluidic devices called electronics-enabled-Point of Care (E-POC) that can quantitate micronutrient markers from whole blood and transmit the data wirelessly to existing mobile phones equipped with near-field communication.

Gregory Moseley, Stephen Rawlinson and David Jans at Monash University in Australia will engineer a live virus with a self-destruct sequence for use in a vaccine. This virus would be identical to a wild-type virus, but contain destabilizing domains fused to key proteins that can be regulated to first allow the virus to replicate and induce an immune response, and then be destroyed.

Jun Zhu and Mark Goulian of the University of Pennsylvania in the U.S. propose to use phage display technology to engineer a commensal “sentinel” bacteria that be introduced into the gut flora. Bacterial toxins would be detected by the sentinel commensal, which would bind to the toxin and express enzymes to destroy it.

Vineet Gupta of the University of Miami in the U.S. will develop a computational model to identify new DNA sequences in the Tuberculosis bacterium that can be used as biomarkers, and then employ zinc-finger tags to detect the identified DNA sequence in a diagnostic test.

Paul Kelly of Queen Mary, University of London in the United Kingdom and the University of Zambia will test the idea that retinoic acid (a form of vitamin A) given with an oral vaccine will boost the mucosal immune response. If successful, vitamin A derivatives could be used as adjuvants for oral vaccines that target childhood diarrhea. In this project’s Phase I research, Kelly was able to demonstrate that retinoic acid enhances gut IgA responses to an oral typhoid vaccine in Zambian adults. In Phase II Kelly seeks to define the mechanisms by which retinoic acid works as an adjuvant, its optimal dosage, whether it works with other vaccines, and whether the effect can be generalized to children in tropical populations with varying degrees of growth impairment.

Aydogan Ozcan of the University of California, Los Angeles in the U.S. will test the feasibility of a lens-free cell phone microscope for rapid, automated and accurate diagnosis of malaria in field settings. This on-chip cell phone microscope is based on digital holography and does not require any lenses, lasers or other bulky components making it extremely cost-effective and compact.

James Shorter of The University of Pennsylvania in the U.S. will engineer enzymes that disassemble protein fibrils found in semen, which are known to allow for the transmission of HIV infection. The ability to reverse fibril formation could block sexual transmission of HIV and provide a new weapon against the global HIV/AIDS pandemic.

Simon Spivack, Albert Einstein College of Medicine in the U.S. will test the theory that DNA of the Tuberculosis bacterium can be detected in exhaled breath. The team will capture exhaled breath condensate samples via a non-invasive device and use nucleic acid amplification to detect the presence of mycobacteria.

Juliana Cassataro of the Universidad Nacional de San Martín-CONICET in Argentina will test whether the bacterial protease inhibitor Omp19 can make vaccines more effective when they are administered orally. Oral delivery of vaccines is far simpler than by injection, which is particularly useful in low-resource settings, and it may also stimulate mucosal immunity making them more effective against some diseases. However, most vaccines administered orally are degraded in the stomach or do not induce a sufficient immune response to protect against the disease. In Phase I, while at the Universidad de Buenos Aires-CONICET, they discovered that Omp19 protects antigens from degradation and serves as an adjuvant, contributing to induction of both a mucosal and systemic immune response in mice orally immunized with proteins from the Salmonella bacterium and the Toxoplasma parasite, both of which have mucosal routes of infection. In Phase II, they will extend their mechanistic studies in order to move towards a Phase I clinical trial, and evaluate the ability of Omp19 to help induce an immune response in mice upon oral vaccination against Enterotoxigenic E. coli (ETEC), which is the most common cause of bacterial diarrhea in children from developing countries.