-Medical
applications of microarray technologies: a regulatory science
perspective
Read the
instructions
that follow below and begin your investigation of the promise
of microarrays in environmental medicine. Answer the questions,
according to your instructor's directions, to demonstrate your
understanding of this new and important
technology
You
are about to begin an Envirohealth WebQuest. Instructions
will appear in RED
and questions to be answered in
BLACK.
Read the directions carefully before going to any sites.
Look at the questions that are to be answered from the
information at a site and use the questions as objectives to
direct your reading and examination of any pages. Toggle
back and forth between the specified sites and these pages.
Use the BACK
and FORWARD
button on your browser bar. Your instructor will explain to
you how they want your data displayed for
grading.
Let's
begin! Click the
green heading
above each section of questions below. It will take you to
your destination. When you arrive there, read
Microarrays
Demystified
. The headings over each of the questions below will
indicate in which section of the page the information is
found to answer the questions.
Microarrays
Demystified
1. Since
1997, the NIEHS Microarray Group has been using microarrays to
analyze changing patterns of gene expression across the entire
genome, studying thousands of affected genes at a time and
revolutionizing the way that toxicologic problems are
investigated.
2.
Using microarrays, researchers can quickly and accurately,
and
3.
By
using an array containing many mRNA samples, scientists can
determine, in a single experiment, the expression levels of
hundreds or thousands of genes within a cell by measuring the
amount of DNA bound to each site on the array.
Medical
treatment tailored to each person's unique genetic make-up and
medical condition
4.
Scientists feel that the use of microarray chips cannot create
medical treatments tailored to each person's unique genetic
make-up and medical condition.
5. The
current problem with microarray use in medicine is reflected in
6.
The
researchers systematically examined the processes involved in
most microarray or gene expression studies, and found that
using a standardized process led to more consistent results.
7.
The
researchers also found that using commercially manufactured
microarrays produced the best results that can be more easily
replicated and that using microarrays made in-house by each lab
gave less consistent results.
8. If
protocols are standardized, then the knowledge gained from
microarray studies
9. When comparing normal
cells and tissues to those known to be diseased, patterns of
gene expression can emerge, allowing scientists to classify the
severity of the disease and to identify the genes that can be
targeted for therapy.
10. In order for microarrays
to be used effectively in the clinic to diagnose patients and
design patient-tailored therapies, they will need to be like
any other clinical tests; they will need to be standardized."
Cutting
Edge Science
DNA
microarrays offer us a "peek under the hood" of the
cell.
11.
Different genes are turned on or off in cells throughout the
body, depending on what that cell is doing. Scientists want to
know
12. By using
microarrays, researchers have started to tease out what they
call "molecular signatures" from cells.
13. Scientists are
confronted with patients responding differently to the same
chemotherapy treatment even though the two patients have, what
appears to be, the same cancer.
14. Being able to use
microarrays to create molecular profiles of tumors appearing to
be visually the same, allows treatments to be customized to the
individual's specific cell differences.
15. The identification of
gene expression signatures has allowed patients to avoid the
toxic aspects of many chemotherapeutic agents and complete
their treatments without the debilitating drug side
effects.
Continue
your Quest with the images and text that follows. Read the
BLACK
TEXT
below. Answer the questions following the
reading.
The Scope
of Microarrays in Treating Human Disease
Data
presented in this Quest, thusfar, seems to point to a rather
straightforward approach in research relevant to human disease.
The analysis and comparison of gene expression patterns
(molecular signatures) in blood samples, surgically removed
tissues or biopsies of normal and diseased specimens. This
simple approach can provide lists of genes correlated with a
disease, a feature that may improve the diagnostic options of
the disease and provide new targets for intervention.
There are
challenging technical aspects to be dealt with such as sample
quality and quantity. Despite these problems biotechnology is
moving forward with microarray development and have produced
chips to assess human diseases such as those listed on the
chart below. The chart has each disease listed with a link to
an information page describing each of the disorders in some
detail. The links are intended for your perusal to enhance your
understanding, but they it is NOT necessary that you
read them now in order to complete this Quest. Look at them now
and continue through the material and questions.
|
Disease
|
Microarray
Type
|
Summary
|
|
Melanoma
|
cDNA
|
Molecular
classification of malignant melanoma
|
|
Colon
cancer
|
Oligonucleotide
|
Grouping of
similar gene expression families and segregation of
pathological samples from the normal.
|
|
Diabetes
type I
|
cDNA
|
Ineffective
differentiation of diabetic T cells.
|
|
Ovarian
Cancer
|
cDNA
|
Comparison of
gene expression patterns in ovarian cancer tissues and
normal ovarian tissues.
|
|
Development
|
Oligonucleotide
|
Comparison of
adult vs. fetal tissue. Identified genes as candidates
as cell maintenance genes.
|
|
Acute
Myeloid Leukemia
Acute
Lymphoblastic Leukemia
|
cDNA
|
Discovered the
distinction between acute myeloid leukemia and acute
lymphoblastic leukemia.
|
|
Alzheimer's
Disease
Alzheimer's
Genetics
|
cDNA
|
Relative to
normal neurons, the neurons of Alzheimer's patients
displaying neurofibrillary tangles showed significant
reduction in several classes of genes that are known
to encode proteins implicated in Azheimer's
neuropathology.
|
On the right
you see a graphic of a healthy human heart, a diseased heart
with cardiomyopathy and an microarray with a probe pattern
displaying results that implicate specific genes as culprits in
the development of this fatal disorder. One more example of the
promise of gene chip technology.
16. The
analysis and comparison of gene expression patterns (molecular
signatures) in blood samples, surgically removed tissues or
biopsies of normal and diseased specimens appears to be a
rather straightforward approach in research relevant to human
disease.
17. The
microarray test results for ovarian cancer show the differences
in gene expression between normal and cancerous ovarian
tissue.
18. The
microarray test results for Alzheimer's disease
showed
19. The
disease of cardiomyopathy is yielding to microarray analysis by
displaying results that implicate specific genes as culprits in
the development of this fatal disorder.
20. The
microarray test results for acute myeloid leukemia and acute
lymphoblastic leukemia was unable to discover the distinction
between the two diseases.
The
Promise...
Your Quest
has taken you on a voyage of discovery. You have by this time
become fairly well versed in some of the details of microarray
technology and its application. The concept of identifying
hosts of different molecules using the protocols of
biotechology holds great promise for the future of medical
diagnostics and pharmacological treatment. The potential is
there, with ingenuity and hard work, to create individual
biochemical and genetic profiles for people that will allow for
customized medical treatments. There are ethical issues here,
as well as personal issues concerning how much anyone wishes to
know about themselves. Many things will be revealed with these
microarray profiles. Some will be good and others not so good.
How this technology will be used will ultimately be in the
hands of the public who will use it.
It is the
hope of the Envirohealth Connections instructors that you have
benefitted from this Quest. We encourage you to continue to
follow the development of envirohealth issues and keep yourself
as informed as possible on medical matters that affect your
life.
This
completes THE PROMISE OF MICROARRAYS. Now, using
Microsoft Power Point, or the software of your choice, create a
slide presentation. Follow the directions of your instructor on
the number of slides and content. The presentation should focus
on the affect of microarray technology on the diagnosis, or
treatment, of a disease. Support your position with the facts
presented in this presentation and other resources.
Good
luck!
The
potential medical applications of microarrays have generated much
excitement, and some skepticism, within the biomedical community.
Some researchers have suggested that within the decade microarrays
will be routinely used in the selection, assessment, and quality
control of the best drugs for pharmaceutical development, as well as
for disease diagnosis and for monitoring desired and adverse outcomes
of therapeutic interventions. Realizing this potential will be a
challenge for the whole scientific community, as breakthroughs that
show great promise at the bench often fail to meet the requirements
of clinicians and regulatory scientists. The development of a
cooperative framework among regulators, product sponsors, and
technology experts will be essential for realizing the revolutionary
promise that microarrays hold for drug development, regulatory
science, medical practice and public health.