Babak Javid of Tsinghua University School of Medicine in China will determine whether drugs that increase the accuracy of protein production in Mycobacterium tuberculosis, which causes TB, can boost the effect of existing TB drugs and thereby shorten the current 6 month treatment period. They hypothesized that resistance to TB drugs is caused in part by the ability of the bacterium to change its proteins by making random errors during their synthesis (known as mistranslation). In Phase I, they proved that this was indeed the case, and performed a screen to identify candidate drugs that improved the accuracy of protein production. In Phase II, they will perform a further screen and test whether the identified compounds can reduce therapy duration in two mouse models of TB infection.

Daniel Roth of the Hospital for Sick Kids in Canada and colleagues will test whether endocrine factors cause stunting in early infancy. They will analyze parathyroid hyperactivity in a cohort of infants from Bangladesh, where stunting is estimated to affect almost half of all children under the age of 5. To uncover the mechanisms responsible for this hyperactivity, they will conduct a vitamin D supplementation trial and analyze maternal, cord, and infant plasma specimens for evidence of dysregulation of the parathyroid-­vitamin D axis. Their goal is to understand the cause of widespread vitamin D deficiency in the region, which is under­-appreciated, and its linkage to early growth retardation.

Kevin Kain of the University Health Network and the University of Toronto in Canada will investigate malaria infections of the placenta to reveal specific roles of the immune response that lead to preterm birth, low birth weight, and stillbirth. This project will focus on discovering biomarkers to identify at-risk pregnancies as well as new interventions to prevent adverse pregnancy outcomes. Funding partners: Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) and Bill & Melinda Gates Foundation.

Peter Gluckman of the University of Auckland in New Zealand and colleagues will test whether intrauterine growth retardation and childhood stunting, which are commonly seen in developing countries, are caused by epigenetic changes that can be corrected in pregnancy and infancy by modifying nutrition. Stunting is associated with many negative outcomes including decreased cognitive ability and immune function. Using epigenetic analyses, and clinical and epidemiological approaches in stunted and control children from Jamaica, Ghana and Singapore they will identify underlying pathophysiological mechanisms of stunting that can act as targets for intervention. The long-­term goal is to prevent infant stunting and its associated adverse consequences.