13 Jun Biomedical research – In class we discussed the importance of finding a biomarker
As promised, here is problem set #2. Note that the questions require logical thought and
imagination more than good memory and good note taking (although your notes will certainly
help you get ideas to answer these questions). Remember, there are no single right answers. Each
question is worth 12.5 points, for a total of 50 points on this problem set.
Please don’t hesitate to come by office hours, or make an appointment with me if you feel that a
particular question is unclear.
Please read these instructions carefully:
Each question should be answered in no more than half a single spaced page. Therefore the
assignment should not exceed two single spaced pages.
Don’t use font smaller than 10 point so that I can read without straining my eyes.
1) In class we discussed the importance of finding a biomarker that can reliably detect heart failure,
especially before major symptoms become obvious to the patient. To answer this question, imagine
that a new biomarker for heart disease is discovered. You read that this biomarker is a protein which
is normally not found in blood, but which appears in 80% of asymptomatic people who will eventually
go on to develop heart disease. The article you read is very positive about this new biomarker and its
potential to save lives, but being a critical thinker you decide to play the role of devil’s advocate. Is
there any potential disadvantage of using this biomarker? Would you ultimately (after considering the
pros and cons) be in favor or against its use? Why?
2) How did Dr. Wang model chronic heart disease in mice? How does this model compare to actual heart
disease in humans? What are some of the disadvantages of using this disease model? Why was this
disease model used despite its flaws?
3) One of the surprising findings in this seminar is that the splicing patterns of diseased heart tissue
mirror the splicing patterns of the developing heart (see slide 15). Remember that we still don’t know
exactly what this means, but this should not stop us from thinking about it. For example, we could
make an argument that the splicing patterns we see in the diseased heart are “damaging” (i.e. casing
the actual damage to the heart). Alternatively we could just as easily say that these splicing patterns
are “protective” (i.e. helping minimize damage to the heart). Notice that these two statements are
starting to look like alternative hypotheses. So, what would you choose as your initial hypothesis? Do
you think that the splicing patterns are “damaging” or “protective”? How would you justify your
choice? Last, conceptually how would you test your hypothesis? (Notice that I say conceptually, so
please don’t focus on experimental techniques. Focus on the logic of your experiment.)
4) Take a look at the hypothetical results seen in figure 1. Here you see a representation of a qRT‐PCR
experiment telling you that tube #2 (diseased heart) contains more of the “heart structural gene” than
tube #1 (healthy heart). You know this because the signal reaches the threshold first in tube #2. If you
take a look at figure 2 you notice that this makes perfect sense as there is more “heart structural
mRNA” in tube #2 to begin with, so you might even feel safe to conclude that indeed the diseased
1
heart produces more of the “heart structural mRNA” and that this change in expression might be
associated with heart disease. Why would this conclusion be flawed? How can the “housekeeping
gene” help you prove the flaw?
[Note: a housekeeping gene is one of the many genes that are expressed more or less equally in all cells
and helps maintain them].
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