BIO360: The Molecular Biology of Cancer
Fall 2014
Take-Home Exam 1
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.
Hedblom, A., K.B. Laursen, R. Miftakhova, M. Sarwar, L. Anagnostaki, A. Bredberg, N.P. Mongan,
L.J. Gudas and J.L. Persson. 2013. CDK1 interacts with RAR and plays an important role in
treatment response of acute myeloid leukemia. Cell Cycle. 12:1251-1266.
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. For example, don’t say “the data are in
Figure 12” but rather say “the data are in the first four lanes of Figure 12C, comparing the western blot
on the top versus the western blot on the bottom”. 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 8. Email submissions
are fine, but still must meet the same deadline.
1. What is the hypothesis that was behind the experiment shown in Figure 1B? What’s the rationale
behind the hypothesis? Based on your analysis of the data, is the hypothesis supported or refuted? Or is
it hard to say? (5 points)
2. Figures 3A and 3B are investigating the affect that ATRA treatment has upon the subcellular
localization of CDK1. Why did the authors do these experiments in U-937 cells? Why were these
scientists interested in ATRA? What are -Tubulin and Lamin B? Why are they included in this
experiment? (5 points)
3. In some cases in Figure 3A, there seems to be two bands in the CDK1 western blots. Why do the
authors think that there are two bands? Does the relative abundance of the two bands stay constant or
change in each of the samples? Might this suggest anything that is biologically important? (5 points)
4. In the abstract, the authors state that the presence of the Cdk1 protein is needed for ATRA to have an
“optimal effect” on leukemic cells. Where are the data in which they evaluate the hypothesis that ATRA
decreases cell cycling but only if Cdk1 is fully expressed? Briefly, how did they measure cell cycling?
Based on the data, is this hypothesis supported or refuted? Where are the data in which they evaluate
the hypothesis that ATRA increases terminal differentiation but only if Cdk1 is fully expressed?
Briefly, how did they measure terminal differentiation? Based on the data, is this hypothesis supported
or refuted? (10 points)
5. Figure 4F shows that knocking down CDK1 expression decreases the number of cells that are
expressing CD11c. The authors contend that this means that CDK1 is needed for the cells to be fully
responsive to ATRA. An alternative explanation is that the CDK1 knockdown decreased expression of
the CD11c gene. Is this alternative explanation consistent with the data? Why or why not? (5 points)
6. In the abstract, these scientists state that “CDK1 modulates the levels of P27 kip and AKT
phosphorylation in response to ATRA treatment.” I have some real concerns about this statement.
Relying on the data that they show us, do we have evidence that either CDK1 or ATRA can affect the
total amount of P27kip protein? Do we have evidence that either CDK1 or ATRA can affect the
phosphorylation state of the P27kip protein? When combined, how do CDK1 and ATRA affect P27kip?
Similarly, do we have evidence that either CDK1 or ATRA can affect the total amount of AKT protein
that is phosphorylated? Is it possible that CDK1 or ATRA affects the total amount of AKT present
without affecting the proportion of AKT that is phosphorylated? (10 points)
7. 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 Hedblom 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 Hedblom et al., Zhang et
al. or Hoare et al.
For example, you might decide to knockdown the expression of the NCC1 gene in cultured cells and
monitor the expression of the Ncc2 protein by western blotting. For this experiment, you don’t need to
report your NCC1 siRNA sequences or how to run a western blot but you should explain why you
expect NCC1 to affect Ncc2 (or why you’d expect no effect!) and what important controls you would
run. (10 points)