BME365R

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University of Texas *

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365R

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Mechanical Engineering

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Dec 6, 2023

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pdf

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6

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1 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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