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| Current Projects Applying Basic Bacteriology to the Global Health Challenges of Infectious Disease Characterizing the in vivo Plasmodium Metabolome The Future of Global AIDS Treatment Multidisciplinary Program on Disease Management: Drug Resistance and Social Norms New Strategies to Detect and Prevent Tuberculosis Potable Water for Global Health Applying Basic Bacteriology to the Global Health Challenges of Infectious Disease PI: Zemer Gitai, Department of Molecular Biology The rise of antibiotic resistance in bacterial pathogens represents an escalating global health crisis. Our lab will help tackle this problem by lending its expertise in bacterial cell biology to identifying new antibiotic drugs and drug targets. More specifically, we will use our understanding of a new set of essential bacterial proteins, the bacterial cytoskeleton, to discover both new families of proteins that are essential for bacterial pathogenesis (candidate drug targets) and small molecules that perturb these proteins (candidate drugs). As a promising proof of principal, we recently identified a small molecule that targets the essential bacterial actin-like cytoskeleton, and preliminary studies suggest that this simple and inexpensive compound can block the growth and virulence of a wide range of human pathogens. Our research will engage a multidisciplinary group of scientists at the undergraduate, graduate, postdoc, and faculty levels. We will also hope to integrate our efforts with those of the greater Princeton community through new inter-disciplinary courses, seminar series, and interest groups.
Characterizing the in vivo Plasmodium Metabolome PI: Manuel Llinás, Department of Molecular Biology Our goal is to understand the metabolic interaction between the malaria parasite, Plasmodium falciparum and the human host during infection. One aspect of this study will rely on patient samples from endemic regions for analysis by mass spectrometry to catalogue the small molecule metabolite levels in infected and uninfected individuals. The methodology for this project is already well established in our lab to look at in vitro cultures of infected red blood cells. A main motivation, therefore is to extend this work to field samples from infected individuals. The results of this study could provide valuable insight toward future therapies aimed at abrogating the severity of disease and ultimately allow us to clear patients of the disease. This research is an ideal platform for an international partnership, because we can provide training here for personnel from abroad (who can then go back and perform these experiments in established locations worldwide), the technological investment is feasible, and the methodologies are easily transferable.
The Future of Global AIDS Treatment PI: João Biehl, Department of Anthropology Unprecedented alliances among AIDS activists, governments, philanthropic and international agencies, and the pharmaceutical industry have made increased access to antiretroviral drugs (ARVs) possible. The battle for access has been hard-fought. Many public- and private-sector treatment initiatives are being launched worldwide, raising a whole new set of national and global healthcare policy challenges regarding adequate drug delivery, sustainable treatment access, and the integration of treatment with prevention. This research and teaching project will address the aftermath of HIV/AIDS treatment rollouts in resource-poor settings, based on Brazil’s model leadership in the efforts to universalize access to AIDS therapies in the mid-1990s. The primary goals are to chart the emerging global networks (comprised of governmental, nongovernmental and industry actors) that are developing around AIDS technology and delivery, and to uncover the new health policies and medical realities emerging in the wake of treatment rollout in select African and Latin American/Carribean countries.
The Integration of Chemistry and Biology to Seed a Next Generation of Malaria and Tuberculosis Therapeutics PIs: Erik Sorensen and Joel Freundlich, Department of Chemistry Professor Erik J. Sorensen and Dr. Joel S. Freundlich are leading a chemistry-driven effort to seed the discovery of novel antitubercular and antimalarial agents. Key to their effort is the development of novel synthetic methodology to efficiently construct complex organic molecules, both natural products and their designed analogs, that have the desired biological activity. Through extensive biology-based collaborations, both at Princeton University and abroad, their goal is to detail the in vitro and in vivo efficacy of these small molecules while thoroughly understanding their mechanism of action. The end result of this research should be both novel biological targets and facilely accessible small molecules that modulate them to achieve the desired antitubercular and/or antimalarial activity.
Multidisciplinary Program on Disease Management: Drug Resistance and Social Norms PIs: Simon Levin and Ramanan Laxminarayan, Department of Ecology and Evolutionary Biology This program addresses aspects of the role of the social context in the management of disease, through two related projects: (1) challenges in drug resistance management; (2) the role of social norms in health care. Incentives and norms are important for determining how infection and drug resistance externalities are addressed in health care. Our overarching goal is to see how incentives and norms interact in the context of clinical practice.
New Strategies to Detect and Prevent Tuberculosis PIs: John Groves and Joshua Rabinowitz, Department of Chemistry This new collaborative program aims to discover and implement novel strategies for the detection and prevention of tuberculosis in humans. The program builds on recent discoveries in the Groves laboratories at Princeton that have elucidated pathways used by virulent mycobacteria to access the iron they need for propagation within human cells. The host-pathogen interaction for tuberculosis is extraordinarily complex since the bacterium exploits some aspects of normal cell function while inhibiting or deactivating others. However, little is known about the iron acquisition and transport pathways adapted by mycobacteria in vivo.
Potable Water for Global Health PI: Winston Soboyejo, Department of Mechanical and Aerospace Engineering Within the developing world, many of the life threatening diseases are water borne. These include diseases such as cholera, dysentery, and typhoid that are transmitted largely by the unclean water that is consumed by more than half of the world’s population. The Grand Challenge Program on Potable Water for Global Health will explore the effects of ceramic water filters on the health and wealth of a community in Africa in which the filters will be made by local people within a community-based enterprise. A combination of fluid mechanics, materials science and biological techniques will be used to study the filtration and pathogen killing mechanisms. The program will conclude by identifying the potential implications of the project for the sustainable development of ceramic water filter enterprises within a global context. The program will engage: Princeton undergraduate/graduate students; Princeton faculty/staff; the Global Development Network at Princeton University, collaborators from Africa, Latin America, as well as development partners and policymakers.
Who Governs the Microbe? Exploring the Emergence of Authority as Response to the Risk of Infectious Disease PI: Evan Lieberman, Department of Politics Within any inhabited territory, people are vulnerable to various types of infections and the onset of disease and death. Any number of governing authorities -- ranging from local governments to international NGOs to traditional healers -- might allocate resources and energies to curb the spread of infectious disease, but across time, space, and infection type, these efforts vary widely. What explains who attempts to govern such problems? To what extent do different infections receive different responses, and why? What are the positive pressures that drive and what are the countervailing pressures that impede aggressive action?
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