1. CBPH 852 Respiratory Question 1, 30 points total
1a. Idiopathic pulmonary fibrosis (IPF), now being termed “Progressive Pulmonary Fibrosis
(PPF) by some, is a devastating diagnosis, with no highly effective drug treatments and a dismal
survival rate after diagnosis. Its prevalence appears to be increasing in aging societies in
developed countries. Lung transplantation (which has many problems of its own) is the only
viable cure.
Preceding a disease with the term “idiopathic” indicates that its cause is unknown. However,
from what we have learned in class, there are now several known genetic causes of pulmonary
fibrosis.
In two concise paragraphs (300 words or less for each example) give two examples of known
genetic causes of fibrotic interstitial lung disease. Your answer for each should indicate the
molecular defect and the likely pathogenesis.
1b. Animal models of disease are critical for understanding disease pathogenesis and for testing
potential therapies. In a third paragraph (limited to 500 words) design experiments that test a
specific point in the pathogenic cascade you illustrate in one of the conditions above. Your
paragraph should include a brief introduction to the question, the purpose of your specific
experiment (including a clear statement of the hypothesis you propose to test), a brief
discussion of the methods (including the animal model that you will use – this can be an existing
animal model, or a novel model – if novel, you can describe its properties, but you don’t need to
include details of how to make it), and finally the expected outcome and its interpretation. If you
wish, you can illustrate the expected outcome with a figure of hypothetical data – the figure will
not count against the word limit.
(30 points total, 8 points each for paragraphs 1 and 2, and 14 points for paragraph 3).
2. CBPH 852 Respiratory Question 2, 30 points total
2a. What are the differences between chronic bronchitis and emphysema? Include anatomical
and morphological changes, as well as descriptions of cellular mechanisms that may be
abnormally activated in both diseases. (half a page single space or one page double space
maximum, 6 points).
2b. Describe the role that mucins play a role in innate defense. Describe how mucins are
deranged in CF lung disease. Include details of how mucin structure plays a role in mucus
function, i.e. clearance of bacteria on the mucociliarly escalator and how dehydration can impact
this mechanism. (half a page single space or one page double space maximum, 6 points).
2c. For your PhD thesis on chronic bronchitis,
Your advisor has agreed to fund the production of one knockout mouse. Which gene would you
choose to knock out, and why? What kind of knockout would you generate (global, conditional,
tissue-specific) and why? Propose one experiment that you could do with this mouse to help
define how your chosen gene participates in the pathological mechanisms that underlie chronic
bronchitis. Describe the experiment in one page or less, including a concise statement of the
hypothesis you are testing, the controls you will perform, and possible pitfalls. Include a figure
showing results that would support your hypothesis, and provide a critical interpretation of those
results. Note that your figure will be based on made-up data (something you are never allowed
to do in the lab!) – construct the figure so that it meets acceptable standards for submission to a
scientific journal – include units, scale bars, labeled axes, a figure legend, etc. Do not use
macrophage elastase (MME) as an example since Dr. Shapiro already did this in the example
paper that I uploaded. (one page single space or two page double space maximum, 12
points for text, 6 points for figure).
3. CBPH 852 Respiratory Question 3, 40 points total
Several of our CBPH852 Respiratory Block classes addressed mucociliary clearance, a critical
respiratory tract innate immune defense mechanism. Cystic fibrosis (CF), chronic obstructive
pulmonary disease (COPD) and asthma are characterized by impaired mucociliary clearance.
3a) Describe the basic parameters determining the efficiency of mucociliary clearance,
discussing its cellular and molecular basis. (limited to 1/2 page, 10 points)
3b) CF is the most common life-limiting genetic disease of the Caucasian population. State the
cause of CF, explain the pathogenesis of the characteristic chronic lung infection, and discuss
the main current approaches to novel therapies directed at the molecular basis of the disease.
(limited to 1/2 page, 10 points)
3c) You are performing basic lab research at the bench and believe that you have discovered a
novel therapy that enhances mucociliary clearance. You think it will be a blockbuster treatment
for CF, COPD and asthma. Outline the pathway for drug development, from your own basic
preclinical studies, intellectual property protection, FDA-required pre-clinical studies, to clinical
trial design, specifying and briefly discussing the key steps along the way. (limited to 1.5
pages, 20 points)
