BIO360: The Molecular Biology of Cancer
Fall 2013
Take-Home Exam 2
The goal of this take-home exam is to assess how well you are able to read and evaluate scientific
literature because this is a central skill that you will need in whatever you do after NCC. For this to
work, it is simply essential that you are the only one answering these questions. Please read the
following statements. If you agree to these provisions, please sign and date below and turn this in with
your completed take-home exam. As always, please ask if something is unclear.
 You may not receive help from another person. This is true for any student enrolled in this
course or from any other person at North Central or elsewhere. The only exception is that you
are encouraged to ask Dr. Johnston for any clarification that is needed.
 You may not provide assistance to any other member of the class. If anyone approaches you
for help with this exam, you are obligated to report that immediately to Dr. Johnston.
 You may use any published material or on-line resource to help you answer the questions, so
long as you do not plagiarize that source. At the end of your answers to the exam questions,
please provide a brief, informal list of all sources that you used.
 Seeking or providing help to another student on the take-home exam will result in your failing
BIO360 and being reported to the Dean’s Office for further disciplinary action, including the
possibility of permanent dismissal from the College.
By signing below, I certify that I have neither received nor provided any help from another person in
completing this assignment. I have read, understood and agree to abide by all of the above terms and
conditions.
Printed Name: ___________________________________________
Signed: _________________________________________________
Date:__________________
Read the following paper and answer the questions below.
Schmidt, V.A., C.S. Chiariello, E. Capilla, F. Miller and W.F. Bahou. 2008. Development of
hepatocellular carcinoma in Iqgap2-deficient mice is IQGAP1 dependent. Mol. Cell. Biol.
28:1489-1502.
Try not to analyze what the authors of the paper say in the text – rather analyze what the data say.
Please type your answers. You are welcome to augment your written answers with hand-drawings if
that helps explain your ideas. Don’t quote this paper or any other. Be sure to refer to specific data
contained in this paper frequently to support your answers. Please put your name only on the signature
page only and not on the paper itself. All answers are due at noon on Wednesday October 23. Email
submissions are fine, but still must meet the same deadline.
1. The authors design, build and confirm an Iqgap2 knockout mouse as documented in Figure 1.
A. In the southern blots shown in Figure 1C, the genomic DNA was digested with ApaI before
being separated by electrophoresis. What result would the authors have seen if they digested the
DNA with XbaI instead of ApaI? What result would the authors have seen if they digested the
DNA with BamHI instead of ApaI or XbaI? (3 points)
B. Four different tissues were analyzed by western blotting for IQGAP2 in Figure 1E. Which one
tissue is most important to show here? Why? (3 points)
C. What hypothesis were the authors evaluating when they ran western blots for IQGAP1 in Figure
1E? What conclusion did they reach about IQGAP1 from this experiment? (4 points)
2. In the abstract, the authors assert that they found “no evidence for direct IQGAP1-IQGAP2
interactions,” meaning that the two proteins don’t bind each other. Where are the data that support this
conclusion? When you analyze the available evidence, do you agree with this conclusion? (5 points)
3. Figure 5D shows that E-cadherin levels are substantially lower in hepatocellular carcinomas than in
untransformed liver tissues from Iqgap2-/- mice. Why didn’t they include livers from Iqgap2+/+ mice on
this western blot? If they had included this wildtype tissue, what result would you expect to find? Or is
it unclear what they might find? Why? (10 points)
4A. The paper goes into detail about how the Iqgap2-/- mice were produced. In Figure 7, the authors
look at double knockout mice, which have the genotype: Iqgap1-/- Iqgap2-/-. How were these double
knockout mice produced? (5 points)
4B. What can we conclude from the Kaplan-Meier curve shown in Figure 7C? (5 points)
4C. The data seem pretty clear that IQGAP2 acts as a tumor suppressor gene in these mice. Would you
classify IQGAP1 as a putative tumor suppressor gene or a putative proto-oncogene for these mice? Or
neither? Or is it unclear? Please explain your answer. (5 points)
5. What else do you want to know? Good papers always tell us something new about the world which
has the effect of raising new questions. Begin by putting forth a specific hypothesis or question. In your
answer, list your hypothesis or question in one sentence and underline that sentence. Design an
additional experiment or two that will significantly extend the results of Schmidt et al. Be original and
don’t just re-state your answer to an earlier question on this exam.
Be sure to explain the rationale behind your hypothesis, briefly outline an experiment or two and show
why the new results will be important. Be very clear about your dependent and independent variables.
In other words, what will you alter and how you will alter it? What will you measure and how will you
measure it? In your answer, cite at least one primary research paper other than the papers that we have
read as a class. (10 points)
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BIO360: The Molecular Biology of Cancer