Our Presentation - BioQUEST Curriculum Consortium

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4 Οκτ 2013 (πριν από 3 χρόνια και 9 μήνες)

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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


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



target audience and required
prior knowledge,


learning objectives,


concepts covered,


student assignments/handouts,


r
equired resources,


s
uggested activities,
implementation.

Lesson guides will include/specify

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.






Model problem space: cholera

Concepts:


Evolution,


Pathways,


Structure
-
function,


Information flow,


Systems


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
)


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

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_200
5_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.


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
idetified

22
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.
cholerae

serogroups

O1 or O139, which produce
cholera toxin (i.e., toxigenic
V.
cholerae

O1 or O139).


The most frequently reported post
-
hurricane
Vibrio
illnesses were
V.
vulnificus

and
V.
parahaemolyticus

wound 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
illnesses

after

Hurricane

Katrina
--
multiple

states
, August
-
September

2005
. MMWR
Morb

Mortal

Wkly

Rep
. 2005
Sep

23;54(37):928
-
31.

Center for Disease Control and Prevention (CDC).
Two

cases

of

toxigenic

Vibrio
cholerae

O1
infection

after

Hurricanes

Katrina
and Rita
--
Louisiana,
October

2005
.
MMWR Morb Mortal Wkly Rep. 2006 Jan 20;55(2):31
-
2
.

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
Vibrio

cholerae

Serogroup

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
Vibrio

cholerae

from Haiti, Asia, and Africa

http://wwwnc.cdc.gov/eid/article/17/11/11
-
0794_article.htm

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

Advanced courses: analysis of gene
expression workflow

Disease

(cholera)

Differentially

e
xpressed genes

Classify genes by function

(Location,

cell process,

molecular function)


ID pathways

Involved/affected


by disease

AMIGO in

Gene Ontology

ArrayExpress

Atlas

1. Explain mech. of disease on

the molecular and cellular levels

2. Propose


Experiments to test mechanisms


strategies for therapies

A promising experiment on cholera in

Expression ATLAS


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
)

Top 10 differentially expressed genes


Reactome

database

Over
-
representation analysis


Unfortunately, none of these pathways exactly leap out as
being over
-
represented


Drosophila
and
C.
elegans

experiments found very few
genes that mapped to pathways

Model organism

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

Heat Map

Sample expression data from ATLAS

http://www.ebi.ac.uk/gxa/experiment/E
-
GEOD
-
35439


Advanced courses: analysis of gene
expression workflow

Disease

(cholera)

Differentially

e
xpressed genes

Classify genes by function

(Location,

cell process,

molecular function)


ID pathways

Involved/affected


by disease

AMIGO in

Gene Ontology

ArrayExpress

Atlas

1. Explain mech. of disease on

the molecular and cellular levels

2. Propose


Experiments to test mechanisms


strategies for therapies

Disease

(cholera)

Differentially

e
xpressed genes

Classify genes by function

(Location,

cell process,

molecular function)


ID pathways

Involved/affected


by disease

Transcription

f
actors involved

AMIGO in

Gene Ontology

Biomart

Sequence 2KB upstream of

Transcription start site

Meme

B
inding sites

for
Txn

factors

ArrayExpress

Atlas

Uniprot

Advanced courses: analysis of gene
expression workflow

make simple models for regulatory networks and try to test their models with other
data

Assessment:

Learning
Obj.:

Students should
be able to

Concept

Common
misconception

Ideas for ways to
assess

1. Use appropriate
sources to find info
(Information literacy)

1B. Peer reviewed
source is more more
trustworthy than
non
-
peer reviewed.

?1C. Expert source
is more trustworthy
than non
-
expert (as
long as its a real
expert with no
conflict of interest
e.g. Dr. X is selling
pill Y that will make
you live forever)

1B and 1C. If it is on
the web, it must be
true

give students X
websites/sources
and ask to evaluate
most appropriate
source of info for a
given question.

Alt: Pose a question,
ask students to find
info and report 3
credible sources
and explain why
these are credible

Learning Obj.:

Students should
be able to

Concept

Common
misconception

Ideas for ways to
assess

1A. Use scientific
databases to find
info.

1A. Curated data
is more trustworthy
than automated
data.

1A. if it is in the
database, it is
correct.

content specific
questions: can
student find X

2. Formulate
questions and
hypotheses.

Patterns in data
can suggest
relationships that
can be tested.

3. Draw
conclusions
supported by
evidence.

Credible
statements in
science must be
supported by
evidence.

correlation implies
causation