1 / 26

Nancy Boury Anya Goodman Jose Monterrubio Srebrenka Robic Liz Ryder Arlin Toro

Investigation of the molecular basis of diseases with bioinformatics tools for students in different stages of training: problem space for cholera. . Nancy Boury Anya Goodman Jose Monterrubio Srebrenka Robic Liz Ryder Arlin Toro.

rasul
Download Presentation

Nancy Boury Anya Goodman Jose Monterrubio Srebrenka Robic Liz Ryder Arlin Toro

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Investigation of the molecular basis of diseases with bioinformatics tools for students in different stages of training: problem space for cholera. Nancy Boury Anya Goodman Jose MonterrubioSrebrenkaRobic Liz Ryder ArlinToro

  2. Goal: Create a framework for engaging biology students in investigation of human disease in classrooms from freshman to senior level. The problem space will include • background info/links/resources/data • data from molecular to population levels • curriculum/lesson guides of varying complexity Intro Bio Genetics Mol.bio Cell Bio Microbiology Genomics Indep. study Capstone

  3. Lesson guides will include/specify • target audience and required prior knowledge, • learning objectives, • concepts covered, • student assignments/handouts, • required resources, • suggested activities, implementation.

  4. Learning objectives for all levels (different depth): Students should be able to • 1. Use appropriate sources to find info (Information literacy) 1A use databases to find info. • 2. Formulate questions and hypotheses from data exploration. • 3. Draw conclusions supported by evidence.

  5. Model problem space: cholera Concepts: • Evolution, • Pathways, • Structure-function, • Information flow, • Systems

  6. Why is clean water important? • Cholera is a well-known hazard • Cholera is a bacteria • Fecal Oral transmission • Cholera Toxin (A-B toxin) • Species Varability • Serovars(different strains within each serovar)

  7. Intro/intermediate level assignments for investigation: 1. Case study investigating cholera outbreak in Haiti after the earthquake – origin of outbreak – relief worker. Another example: Katrina 2. Some people are resistant to cholera– genetic basis of that? http://www.cbsnews.com/8301-504763_162-20020850-10391704.html

  8. Intro/intermediate level assignments for investigation: 3. Cholera toxin protein structure – understand how it causes disease, how this fold evolved, how it relates to other toxins. 4. Explore the evolutionary relationship between the bacterium and phages encoding the toxins. molecule of the month 10.2210/rcsb_pdb/mom_2005_9

  9. The 2010 Earthquake in Haiti • Photos • Destruction of Infrastructure • Cholera Casualties • 534,647 cases resulting in 287,656 hospitalizations, and 7,091 deaths have been reported in Haiti as a result of the outbreak.

  10. Katrina outbreak Hurricane Katrina made landfall on August 29, 2005, with major impact on the U.S. Gulf Coast. During August 29–September 11, surveillance idetified22 new cases of Vibrio illness with five deaths in persons who had resided in two state (Figure 1) Cholera is a severe diarrheal illness caused by V. choleraeserogroups O1 or O139, which produce cholera toxin (i.e., toxigenic V. choleraeO1 or O139). The most frequently reported post-hurricane Vibrio illnesses were V. vulnificusand V. parahaemolyticuswound infections. These cases represent an increase over the normal reported incidence of Vibrio wound infections in Gulf Coast states and are consistent with exposure after hurricane landfall.Illness likely resulted from infection of a wound or abrasion acquired before or during immersion in floodwaters. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm54d914a1.htm#fig1 Centers for Disease Control and Prevention (CDC).Vibrio illnessesafterHurricane Katrina--multiplestates, August-September 2005. MMWR MorbMortalWklyRep. 2005 Sep 23;54(37):928-31. Center for Disease Control and Prevention (CDC).Twocasesoftoxigenic Vibrio cholerae O1 infectionafterHurricanes Katrina and Rita--Louisiana, October 2005. MMWR Morb Mortal Wkly Rep. 2006 Jan 20;55(2):31-2.

  11. Data, resources, links: 1. Cholera in Haiti : The Origin of the Haitian Cholera Outbreak Strain - NEJM article http://www.nejm.org/doi/pdf/10.1056/NEJMoa1012928 2. Notes from the Field: Identification of VibriocholeraeSerogroup O1, Serotype Inaba, Biotype El Tor Strain — Haiti, March 2012 MMRW May 4, 2012 / 61(17);309-309 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6117a4.htm 3. Preoteopedia cholera toxin link http://www.proteopedia.org/wiki/index.php/1xtc 4. Cholera toxin molecule of the month Link to “molecule of the month” on pdb http://www.rcsb.org/pdb/101/motm.do?momID=69 5. Vibrio cholera database at Broad Institute http://www.broadinstitute.org/annotation/genome/vibrio_cholerae/MultiHome.html 6. Comparative Genomics of Vibriocholerae from Haiti, Asia, and Africa http://wwwnc.cdc.gov/eid/article/17/11/11-0794_article.htm

  12. Cholera Problem Space in an Upper level Bioinformatics class • Revisit the Cholera Problem Space • Have students perform the alignment and phylogenetic tree generation from the paper from the Intro course • Ask students to find an experiment related to cholera in Expression ATLAS • Hypothesize pathways that might be enriched for differentially expressed genes • Perform the analysis and interpret data • Pick an enriched pathway and explore it

  13. Advanced courses: analysis of gene expression workflow AMIGO in Gene Ontology ArrayExpress Atlas Disease (cholera) Differentially expressed genes Classify genes by function (Location, cell process, molecular function) Reactome ID pathways Involved/affected by disease • 1. Explain mech. of disease on • the molecular and cellular levels • 2. Propose • Experiments to test mechanisms • strategies for therapies

  14. A promising experiment on cholera in Expression ATLAS

  15. Nice, simple, one factor set up • Mouse dendritic cells • Cholera toxin, forskolin, control media • In mice – should have nice annotated pathways • Looked at top 400 genes (p values 10-6 to 10-4)

  16. Top 10 differentially expressed genes

  17. Reactome databaseOver-representation analysis • Unfortunately, none of these pathways exactly leap out as being over-represented • Drosophila and C. elegansexperiments found very few genes that mapped to pathways

  18. Model organism

  19. Experiment compared gene expression in two fly mutants with different susceptibility to cholera

  20. Heat Map

  21. Sample expression data from ATLAS http://www.ebi.ac.uk/gxa/experiment/E-GEOD-35439

  22. Advanced courses: analysis of gene expression workflow AMIGO in Gene Ontology ArrayExpress Atlas Disease (cholera) Differentially expressed genes Classify genes by function (Location, cell process, molecular function) Reactome ID pathways Involved/affected by disease • 1. Explain mech. of disease on • the molecular and cellular levels • 2. Propose • Experiments to test mechanisms • strategies for therapies

  23. Advanced courses: analysis of gene expression workflow AMIGO in Gene Ontology ArrayExpress Atlas Disease (cholera) Differentially expressed genes Classify genes by function (Location, cell process, molecular function) Reactome Biomart Sequence 2KB upstream of Transcription start site ID pathways Involved/affected by disease Uniprot Meme Binding sites for Txn factors Transcription factors involved make simple models for regulatory networks and try to test their models with other data

  24. Assessment:

More Related