Knowledge Generation

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.

Jennifer Friedman of the Center for International Health Research at Rhode Island Hospital in the U.S. will examine the role that chronic placental and fetal exposure to infectious diseases during gestation plays in low birth weight. This work will form the basis of further studies to identify biomarkers for fetal inflammation in the maternal circulation for possible use in diagnostic tests to identify at-risk pregnancies.

William Hay of the University of Colorado Denver in the U.S. will use multiple types of nutritional interventions in a sheep model of placental insufficiency to test the hypothesis that there is a window of opportunity to prevent intrauterine growth restriction (IUGR). Better understanding of the mechanisms underlying IUGR could help explain why nutritional intervention sometimes fails and could lead to better outcomes for infants in low-resource areas.

Andrew Patterson and Gary Perdew of the Pennsylvania State University in the U.S. will investigate the ability of the aryl hydrocarbon receptor (AHR) to modulate intestinal inflammation and general intestine health, and they will test in a mouse model whether natural AHR activators given to nursing mothers provide protection to pups from experimental intestinal inflammation.

Lin Xi and Jack Odle of North Carolina State University in the U.S. propose to use metabolomic and epigenetic analysis in a pig model to explore the mechanisms by which dietary choline and DHA (docosahexanoate) supplementation in gestating mothers could alleviate the effects of malnutrition on infants. The data could inform the design of nutritional supplements for mothers to improve the developmental outcomes of low birth weight infants.

Laura Woollett of the University of Cincinnati in the U.S., in collaboration with the MRC International Nutrition Group in The Gambia, will test whether increasing plasma cholesterol in pregnant mothers from developing countries can improve fetal growth rates and reduce the associated risk of mortality and developmental defects. They hypothesized that the high incidence of low birth weight in developing countries is caused by lower levels of cholesterol in pregnant women.