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Application
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Bad Hygiene or Bad Bug? (Investigation of C. difficile outbreak and toxicity using bioinformatics tools, case-based approach, and molecular genetics simulation using CaseIt software; linked with Project 2 above)
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Entry level courses in biology or microbiology |
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Investigation of the molecular basis for strain differences in Clostridium difficile pathovars associated with recent outbreaks of severe C. difficile-associated disease in North America. |
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Currently a few tcdC sequences from outbreak-related and historical C. difficile strains, obtained from GenBank (NCBI). |
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(1) McDonald et al, New England Journal of Medicine 353(23): 2433-41, Dec. 2005. This paper presents evidence that outbreak-associated strains have a deletion in the gene for a down-regulating protein that controls expression of a pair of toxin genes, and share also antibiotic resistance and other features. (2) Case It! http://caseit.uwrf.edu/, a source of software that provides simulation of restriction digestion, PCR, Southern blotting, and PFGE (in silico performance of experiments that were used to generate data relevant to the case). These methods are currently prominent in epidemiological investigations involving C. difficile. (3) Biology Workbench Biology Workbench http://workbench.sdsc.edu. This resource facilitates use by novices of DNA and protein sequence analysis tools for generating multiple sequence alignments, rooted & unrooted trees, and other goodies. (4) NCBI http://www.ncbi.nlm.nih.gov/entrez/, resources such as BLAST & PubMed for finding and downloading DNA sequence data and related materials and locating relevant journal articles. |
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Write a finished case incorporating these materials to be used in classroom settings and for dissemination to interested teachers. This includes generating text for background and other support documents, identifying additional print resources students can use, collecting a dataset of sequences of relevant C. difficile genes from various sources, both historical and outbreak-related, and fleshing out the interfaces between the case documents and the Case It! and Biology Workbench tool collections. |
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