BME365R.2022.HW1

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Dec 6, 2023

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1 BME 365R: Engineering Physiology I Fall 2022 HOMEWORK 1 Use this space to list your collaborators and which question #’s you worked on together. Firstname Lastname (Question #)

2 Cell Histology and Morphology 1. As an undergraduate research assistant, you are working in a lab that studies the biology of various types of epithelial cells. You have learned to prepare tissues for imaging by electron microscopy. a. Describe three advantages of electron microscopy over light microscopy. (3 points) b. Describe three disadvantages. (3 points) c. Unfortunately, in your first attempt to prepare samples you use a Crayola marker to label the slides, instead of a permanent lab marker. All of the labels wash away upon exposure to fixative. Trying to salvage the materials, you send the samples off for EM imaging anyway and receive back the following description from the pathologist. “ …Epithelial cells are columnated. They exhibit tight functions. Cilia are visible on the apical surface of the cells.” What tissue does this sample correspond to? Explain your answer. (6 points) 2. Write your own question about identifying tissues and cells from structure and morphology. Following the style of question 1C above, write your own question about a researcher who has neglected to label some slides. Describe properties of the sample that are observed by EM or phase contrast or fluorescence microscopy. You may provide as many “clues” as you like. Then, provide an answer key with an explanation. (8 points)

3 Cell Membranes 3. 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)

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4 Nuclear Structure 4. You are a medical student at a children’s hospital and meet a 7-year-old patient with the rare disease Hutchinson–Gilford progeria syndrome (HGPS). This disease is associated with tissue changes that resemble accelerated aging, including reduced tissue growth, bone fragility, decreased subcutaneous fat, atherosclerosis and heart disease, including cardiomyopathy. You learn that the disease is caused by a mutation in the gene that encodes lamin A, an intermediate filament protein that is found in the cell nucleus. Upon further reading, you learn that the mutation responsible for this patient’s disease is a silent mutation in the gene encoding lamin A. This is the most common mutation in HGPS and is observed in ~80% of affected individuals. A. What is a silent mutation? (2 point) B. Describe 2 different mechanisms by which silent mutations might have an impact on protein or cell function. (6 points) C. The defective version of lamin A protein results in unstable cell nuclei with disturbances in chromatin organization, mitosis, DNA replication and repair, and gene transcription. We’re going to be learning quite a lot more about this disease for Project 1, SO please demonstrate your skills in primary literature searching by finding 2 recent scientific papers (published in the past 5 years) on Hutchinson– Gilford progeria syndrome. One paper should be a review style manuscript and one should be a primary research study that reports new data. Paste the citations for each below and state what information you might expect to learn from each paper. You do not need to read the entire papers—you might decide to later when you start working on Project 1! (8 points)

5 Cytoskeletal Structure 5. For each of the features below, write the name of the corresponding cytoskeletal fiber. (1 point each) Feature Cytoskeletal fiber A solid fiber measuring ~7 nm in thickness A hollow fiber with an ~15 nm luminal diameter A solid fiber measuring 8-12 nm in thickness A major structural component of cilia and centrioles For each of the features below, write the name of the corresponding cellular junction. (1 point each) Feature Junction Seals the space between 2 adjacent epithelial cells A site of epithelial attachment of the basal lamina Facilitates intercellular communication by small molecules An intercellular junction connected to intermediate filaments