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BME 365R: Engineering Physiology I
Fall 2022
HOMEWORK 2
Use this space to list your collaborators and which question #’s you worked on
together. This assignment includes links to additional required reading so plan
your time appropriately.
Firstname Lastname (Question #)
2
1. Cell Membranes
A 5-year-old child presents with a history of recurrent bacterial infections. During each
infection, there is an appropriate increase in his total white cell count (including
neutrophils), but his biopsies show very few neutrophils at the sites of infection.
You suspect that this patient suffers from a rare genetic disorder called leukocyte
adhesion deficiency, caused by a mutation in the gene
ITGB2
.
This gene encodes a
subunit of the β2
– integrin protein.
A.
Where are functional integrin proteins located in mammalian cells? (2 point)
B.
Integrins assemble into heterodimers, each consisting of one alpha and one beta
subunit.
What level of protein structure does this represent?
(2 points)
C. Among patients with leukocyte adhesion deficiency, mutations in
ITGB2
fall into
two main categories.
Class 1 mutations are deletions and insertions in the
ITGB2
sequence while Class 2 mutations are missense mutations.
How do you
expect the protein levels of ITGB2 to differ in Class 1 versus Class 2 patients?
(6 points)
D.
How would a missense mutation in the
β2
– integrin ectodomain impact function
of the integrin?
In the endodomain?
(6 points)
3
2.Cystic Fibrosis
Mary is a 19 year old woman who has been diagnosed with this genetic disease. Her
past laboratory findings include a positive sweat test and an elevated concentration of
chloride ions.
She frequently suffers from bacterial infections and digestive ailments.
Over time, Mary’s lung function has reduced to 28% of normal.
A.
To measure lung dysfunction, it is first necessary to establish values for normal lung
function. Often we may not be aware of the underlying factors that were part of the
decisions in setting these values.
Read the following 2 brief commentaries and explain how the values for normal lung
function were determined in each study.
How might this impact clinical care?
(3-4 sentences each, 10 points each)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631137/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136072/
B.
CF is primarily caused by one of several DNA mutations. What protein is affected by
the mutation?
Describe the normal function and location in the cell of this protein.
(5 points)
C.
How do the different mutations in the gene affect the structure of the protein?
(suggest at least two mechanisms)
(5 points)
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