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Senior Scholar Award in Global Infectious Disease
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Gary K.
Schoolnik,
M.D.
Stanford University School of Medicine
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The Molecular Ecology of Vibrio cholerae in the Gangetic Delta—Whole genome expression profiles as ecosystem bioprobes
The legendary capacity of Vibrio cholerae, the agent of Asiatic cholera, to spawn global epidemics, is well known to medical historians. Its epicenter is the delta formed by the confluence of the Ganges and Brahmaputra rivers in Bangladesh. There, localized outbreaks occur most years at the end of the monsoon season. Between outbreaks of human disease, the organism resides as a normal component of the rivers, estuaries and ponds that comprise this vast delta system. Within this aquatic habitat, V. cholerae exhibits a surprisingly complex life cycle. It attaches to and digests the chitin-containing exoskeletons of small crustacea. It forms a symbiotic partnership with a variety of algae, scavenging their photosynthetic products. And, it forms surface-attached consortia with other aquatic microorganisms on a variety of submerged objects. Taken all together, these observations suggest the following: physicochemical changes in delta water at the end of the monsoon season transform V. cholerae from a stable member of this ecosystem to a rapidly-transmitted agent of human disease.
While the details of every infectious agent differ, a common theme of many in the “emerging and resurging” group is their capacity to reside quiescently for years in natural environmental reservoirs until changing circumstances transform the organism into a threat to human health. This project will study this quite general phenomenon by correlating the physiological state, biomass, infectivity and virulence of V. cholerae with features of the Ganges delta climate. By using the recently completed DNA sequence of V. cholerae and microarray expression profiling, climate-dependent events will be captured at the genome-level of resolution. Genes of the organism that are activated during V.cholerae’s association with copepods or algae, and in biofilms, will be identified by whole genome microarray expression profiling using laboratory-based microcosms that simulate components of its natural aquatic habitat. Proof that the identified genes are functionally important will be ascertained by measuring the environmental fitness of mutants and the expression state of these genes in nature will be determined using specimens collected in Bangladesh. From these data, we hope to learn how to deduce the effect of climate on an ecosystem from the expression state of individual genes; to use gene expression data to predict outbreaks of human disease; and to gain insight into how bioremediation of this ecosystem might reduce this infectious disease threat.
Contact
Dr. Schoolnik.
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