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Mote Marine Laboratory is undertaking a coordinated, multi-disciplinary study to determine the ecological health of Charlotte Harbor, southwestern Florida. The study builds on Mote's history of pioneering research in the Harbor, present expertise in specific research areas, and access to cutting-edge technology. Five research centers of the Laboratory are actively involved in this comprehensive program. The research honors the memory of William R. Mote, and his interest in Charlotte Harbor, through significant advances in basic and applied science, and the sustainable management of Charlotte Harbor. Charlotte Harbor on Florida’s southwest coast is one of the state’s last large and relatively healthy estuaries. It is vulnerable to projected future population growth and land development, so there is a pressing need for Harbor-wide health assessments and indicators that can communicate to the public how the ecosystem works, and whether the Harbor is declining or improving. Mote Marine Laboratory believes the most effective solution to this problem in the long run will be to develop the ability to predict how the estuary will respond to human-caused stress through studies of how the estuary presently responds to natural stress. An undertaking of this scope represents a scientific milestone for Mote Marine Laboratory because it will for the first time make possible interactive, cooperative research among talented new and experienced scientists. A second significant benefit to Mote will result from the community outreach, advisory committee input, and educational opportunities resulting from the study. The proposed study encompasses all of Charlotte Harbor. The project will require at least five years to conduct. Aspects of the study may continue beyond five years. The project is drawing on satellite imagery and remote sensing, automatic sampling and measurement devices, acoustic, radio, and satellite telemetry, underwater video and geographic information systems. Objectives of the overall program are to: identify sentinel species of estuarine health, and the flora and fauna upon which they rely for habitat, nursery, and food; describe populations and food-webs relative to natural background variation of the physical and chemical environment; account for species and ecosystem responses to natural and anthropogenic (human-caused) perturbations; and develop a predictive capacity relating changes to estuarine health that may be expected as a consequence of future management decisions.