1994 — 1995 |
Brown, Steven H. [⬀] |
F38Activity Code Description: To provide opportunities for scientists to make major changes in the direction of research careers for the purpose of engaging in the synthesis, organization, and management of knowledge. |
Clinical Test of Umls and Problem Statement Closure |
0.923 |
1999 |
Harvey, H. Rodger (co-PI) [⬀] Tenore, Kenneth Anderson, Robert Haasch, Mary Brown, Steven |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Fsml: Upgrading Seawater Filtration Capabilities to Enhance Support of Research Using Seawater System Facilities @ University of Maryland Center For Environmental Sciences
This project will support the upgrade of the seawater filtration capabilities of the sea water system at the Chesapeake Biological Laboratory (CBL) to provide enhanced support research programs involving culturing of marine organisms. The controlled experimental research that characterizes much of today's activities at marine laboratories includes leading-edge biochemical/molecular and physiological/bioenergetic research on the ecology of marine organisms. The nature of the sea water systems at marine laboratories have evolved from simple supply of, at most, coarse-filtered sea water to holding tanks and aquaria to fairly sophisticated systems that must provide fine-filtered and temperature-regulated sea water to support the experimental studies underlying that research. Over the last decade the sea water and laboratory support facilities at CBL in its Truitt Controlled Environmental Laboratory(CEL) have been redesigned, reconfigured, and engineered to provide the treatment components that support experimental needs. Many of the research programs carried out at CBL in the fields of ecology/oceanography, aquatic toxicology, and environmental chemistry/geochemistry depend on the high quality of temperature-controlled and filtered sea water provided to support the experimental studies of marine organisms in the Truitt Controlled Environment Laboratory.
However, the present filtration equipment is inadequate for the larger demand and more stringent quality requirements for filtered sea water to support the research needs currently underway and anticipated growth in the near future. Maintenance of the present system is also labor intensive. This project would replace the current sand filter system with a membrane- Based micro-filtration system that will double the present volume of filtered water (from 50 to 100 gpm) and greatly increase suspended particle removal (from>5 to 1 micron). The new system will eliminate inadequate especially during summer months when research demand for filtered water is especially high and the need for downtime and labor-intensive and costly media changes using the present pressure sand filter technology.
|
0.954 |
2017 — 2018 |
Brown, Steven David [⬀] Brown, Steven David [⬀] |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Engineered Probiotics and Bile Acid Metabolism in the Gut Microbiome @ University of California, San Diego
Project Abstract Although the gut microbiome is an independent environmental contributor to both obesity and diabetes, the biochemical mechanism(s) underlying the microbiome?s effects on these diseases are unclear. Mouse models have suggested that dysbiosis may affect host metabolism through altered bile acid (BA) signaling. Recent studies have shown that BA signaling is necessary for microbiota-induced dysmetabolism and that it plays an important role in the gut?s control of glucose homeostasis. Therefore, manipulation of BA signaling by the gut microbiome may have therapeutic potential in obesity, type 2 diabetes, and non-alcoholic fatty liver disease. One method to understand the functional role of the microbiome is to use engineered probiotics (EnProbs), commensal bacteria that can colonize the gut of the host and can be genetically manipulated to express enzymes of interest. The primary hypothesis of this proposal is that manipulation of the gut microbiome with EnProbs will help determine the functional role of gut microbiota in BA signaling and host metabolism. Three biochemical transformations will be investigated as part of this proposal: deconjugation by bile salt hydrolase (BSH), 3? sulfonation by SULT2A1, and 7?-dehydroxylation (7DH) by a microbial multigene operon. Hydrolysis of the BA side chain amino acid by BSH is the first step toward secondary BA metabolism. Sulfonation of BAs by BAS blocks reabsorption from the lumen. In metatranscriptomic data of the gut lumen, the 7DH pathway was overrepresented in an obesity-protective feeding paradigm. Preliminary results show that EnProbs marked with fluorescence and expressing BSH can colonize wild-type C57Bl/6 mice for more than a week after a 48 hour gavage. In this proposal, a series of EnProbs expressing BSH, SULT2A1, and a 7DH operon or their catalytically- inactive controls will be introduced into healthy and disbiotic mice. First, the response of the gut microbiome composition and luminal metabolites to EnProb colonization in wild-type mice will be assessed by 16S sequencing and LC-MS. Enrichment with specific enzyme activity should produce corresponding biochemical changes in the luminal metabolite pool, but subsequent effects on the luminal microbial ecology and metabolites are unknown. Second, the effects of the enzymatically-active BSH EnProbs on host BA signaling, insulin sensitivity, lipid and glucose metabolism, and whole-body metabolism will be assessed using the diet-induced obesity mouse model and leptin-knockout (ob/ob) mice. Developing and using EnProbs to identify the role of the gut microbiome expands our ability to (1) understand the role of the gut microbiome in metabolism and (2) manipulate the function of the gut microbiome to achieve a health benefit.
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0.911 |