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Non-communicable diseases (NCDs) now account for the majority of global morbidity and mortality and are increasingly affecting developing countries whose under-resourced health care systems also have to handle a high burden of infectious disease. To counter the global devastation caused by NCDs, the United Nations General Assembly decided to "set a new global agenda" and convened a high-level meeting on NCDs in September 2011. In connection with this meeting, the authors of this article took a first step toward developing a policy research agenda for improving access to NCD medicines in developing countries, a step that the research-based pharmaceutical industry, in particular, can carry forward as part of broader global efforts to combat NCD. The authors provide a framework for understanding the obstacles to access for NCD medicines, review specific issues to be confronted within each obstacle in the developing world, identify promising ideas for improving access to NCD medicines, and point to several highly promising areas for the research-based pharmaceutical industry to focus on as it develops its NCD policy research program in close collaboration with other key stakeholders.

To provide accurate biological hypotheses and elucidate global properties of cellular networks, systematic identification of protein-protein interactions must meet high quality standards.We present an expanded C. elegans protein-protein interaction network, or 'interactome' map, derived from testing a matrix of approximately 10,000 x approximately 10,000 proteins using a highly specific, high-throughput yeast two-hybrid system. Through a new empirical quality control framework, we show that the resulting data set (Worm Interactome 2007, or WI-2007) was similar in quality to low-throughput data curated from the literature. We filtered previous interaction data sets and integrated them with WI-2007 to generate a high-confidence consolidated map (Worm Interactome version 8, or WI8). This work allowed us to estimate the size of the worm interactome at approximately 116,000 interactions. Comparison with other types of functional genomic data shows the complementarity of distinct experimental approaches in predicting different functional relationships between genes or proteins

To initiate a system-level analysis of C. elegans DAF-7/TGF-beta signaling, we combined interactome mapping with single and double genetic perturbations. Yeast two-hybrid (Y2H) screens starting with known DAF-7/TGF-beta pathway components defined a network of 71 interactions among 59 proteins. Coaffinity purification (co-AP) assays in mammalian cells confirmed the overall quality of this network. Systematic perturbations of the network using RNAi, both in wild-type and daf-7/TGF-beta pathway mutant animals, identified nine DAF-7/TGF-beta signaling modifiers, seven of which are conserved in humans. We show that one of these has functional homology to human SNO/SKI oncoproteins and that mutations at the corresponding genetic locus daf-5 confer defects in DAF-7/TGF-beta signaling. Our results reveal substantial molecular complexity in DAF-7/TGF-beta signal transduction. Integrating interactome maps with systematic genetic perturbations may be useful for developing a systems biology approach to this and other signaling modules.