1University, Department, Street Address, City State Zip/Post Code, Country LB5

Authors Last Names

[BC1]

Title[LB2]

Author1[BC3]and Author2[LB4]

1University, Department, Street Address, City State Zip/Post code, Country[LB5]

2University, Department, Street Address, City State Zip/Post code, Country

(email address; email address[LB6])

Many undergraduate students in introductory biochemistry courses find it challenging to understand how different levels of protein structure relate to each other. To address this problem, we introduced an inquiry-based laboratory exercise in which students are challenged to explain how the effects of mutations on different levels of protein structure lead to changes in protein function and ultimately to genetically-inheritable diseases. The implementation of this exercise in a large, second-year undergraduate, introductory biochemistry course led to a high level of student satisfaction and a more integrated view of biochemistry and genetics[LB7].[BC8]

Firstpage

Keywords[BC9]: protein structure, biochemistry, genetics, inquiry-based learning[LB10]

Proceedings of the Association for Biology Laboratory Education, Volume 38, 20171

Authors Last Names

Introduction[BC11][LB12]

Ma[LB13]ny undergraduate students in introductory biochemistry courses find it challenging to understand how different levels of protein structure relate to each other. To address this problem, we introduced an inquiry-based laboratory exercise in which students are challenged to explain how the effects of mutations on different levels of protein structure lead to changes in protein function and ultimately to genetically-inheritable diseases. The implementation of this exercise in a large, second-year undergraduate, introductory biochemistry course led to a high level of student satisfaction and a more integrated view of biochemistry and genetics.

Secondary Heading[LB14]

Tertiary Heading[LB15]

Quaternary heading[LB16]

Proceedings of the Association for Biology Laboratory Education, Volume 38, 20171

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Student Outlin[LB19]e[BC20]

Objectives[LB21]

Use bioinformatics tools[LB22]

Evaluate DNA sequence variations in specific genes

Describe molecular basis for inherited diseases

Introduction

As first demonstrated ina classic paper by Linus Pauling and co-workers (1949), mutationsin hemoglobin lead to changes in protein structure,which in turn lead to a molecular explanation for the developmentof an important human disease, sickle-cell anemia. Since this classic study, many other papers have describedexamples of mutations that lead to changes in protein structures,and which in turn lead to the development of diseases (Steward et al. 2003). Over the next few weeks, you will have the opportunity to gain, using various bioinformatics tools, a structural perspectiveon the molecular basis of genetically-inherited diseases. As you saw in your introductory genetics course, human genetically-inheriteddiseases are caused by DNA sequence variations. Although disease-causing DNA sequence variations can occur inboth non-coding and coding regions of the genome, the majority of characterized mutations occur in the coding region of genes.Since they can be found in the coding region of genes, these mutations often affect the structure and function of proteins. Forthis laboratory exercise, we will focus on genetically-inheritable diseases that are caused by this type of mutation. More specifically,we will focus on genetically-inheritable diseases that result from a missense mutation. Recall that a missense mutation is achange in the nucleotide sequence of a gene, where one or more nucleotides is or are replaced by another. This mutation resultsin a new codon, which causes a different amino acid to be inserted into the growing polypeptide chain during translation.For this laboratory exercise, you will be asked to work with your laboratory partner. You and your laboratory partner willbe guided in the use of various bioinformatics tools to study the effects of disease-causing mutations on protein structure andfunction. We will specifically focus on different levels of protein structure and how they are intimately related to one anotherin the formation of the final, fully-folded protein. At the end of this exercise, you and your laboratory partner will be asked toorally present your results to the other members of your laboratory session via a 10-minute Power Point presentation.

Methods and Data Collection

Part A: Selecting Your Topic[LB23]

The first part of this project involves selecting your topic. There are eleven topics from which to select, and only one pair perlaboratory section can work on each topic. So, topic selection is first come, first served. All eleven available topics are listed inAppendix A. Also included in Appendix A are the protein structure coordinates for the wild-type protein and a file with a “.pse”file name extension. You will need this file for your work with the protein visualization software PyMOL. Appendix A alsocontains one seed reference for each disease, to help you get started in locating background information on your topic as wellas structural information and the disease-causing mutation.

Part B: Studying the Protein Structure and Physiochemical Properties

To help you complete your project, you will be guided through all of the steps using the K-Ras protein, which has been implicatedin lung cancer. To make it easier for you, screenshots using the K-Ras example have been inserted in the text below.

Data Analysis[LB24]

Insert text as appropriate.

Discussion

Over the next few weeks, you will have the opportunity to gain, using various bioinformatics tools, a structural perspectiveon the molecular basis of genetically-inherited diseases. As you saw in your introductory genetics course, human genetically-inheriteddiseases are caused by DNA sequence variations. Although disease-causing DNA sequence variations can occur inboth non-coding and coding regions of the genome, the majority of characterized mutations occur in the coding region of genes.Since they can be found in the coding region of genes, these mutations often affect the structure and function of proteins. Forthis laboratory exercise, we will focus on genetically-inheritable diseases that are caused by this type of mutation. More specifically,we will focus on genetically-inheritable diseases that result from a missense mutation. Recall that a missense mutation is achange in the nucleotide sequence of a gene, where one or more nucleotides is or are replaced by another. This mutation resultsin a new codon, which causes a different amino acid to be inserted into the growing polypeptide chain during translation.For this laboratory exercise, you will be asked to work with your laboratory partner. You and your laboratory partner willbe guided in the use of various bioinformatics tools to study the effects of disease-causing mutations on protein structure andfunction. We will specifically focus on different levels of protein structure and how they are intimately related to one anotherin the formation of the final, fully-folded protein. At the end of this exercise, you and your laboratory partner will be asked toorally present your results to the other members of your laboratory session via a 10-minute Power Point presentation[BC25].

Cited References[LB26]

Pauling L, Itano HA, Singer SJ, Wells IC. 1949.Sickle cell anemia: a molecular disease. Science. 110:543-548.

Steward RE, MacArthur MW, Laskowski RA, Thornton JM. 2003. Molecular basis of inherited diseases:a structural perspective. Trends in Genetics. 19(9):505-513.

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Materials[BC27]

[LB28]

A computer with Internet access and the PyMOL[LB29] program(educational version freely available for download from) is required for each pairstudents. LCD projector and computer are required for studentpresentations.

Often, this section will consist of a list of materials, equipment and supplies required conduct your laboratory study with a typical class of 20-30 students. Provide vendor information and current costs as appropriate.

Notes for the Instructor[LB30]

One of the major challenges that we faced in implementingan inquiry-based exercise in a large class of over 500students was to organize the exercise in a way that maximizedthe inquiry experience of each student without placingexcessive demands on the limited time and resources ofa small team of graduate teaching assistants, librarians andinstructors.

Several design elements of the exercise werespecifically chosen to meet this significant challenge.First, an introductory computer-based workshop sessionis conducted during a regularly scheduled, weekly laboratorysection of the introductory biochemistry course. Therelatively small groups of students in individual laboratorysections (approximately 22 students in each of 24 laboratorysections) facilitated the interactive nature of the computer- basedexercises by providing opportunities for one-on-oneinteractions with teaching assistants and librarians, as wellas peer-to-peer learning.Following this introductory session, students are given six weeks to complete the remaining self-guidedexercises and to prepare their Power Point presentation,before the final student presentations.

One of the most difficult challenges facing this projectwas to devise a way to evaluate how students performedin the inquiry-based exercises. Since the oral presentationwas designed to be the culmination of the student-initiatedinquiry-based learning process, the overall performance ofthe students in this exercise was evaluated by marking thequality of the oral presentations for each pair of students. Tostandardize the evaluation of students in a large number ofseparate laboratory sessions, we developed a detailed markingrubric that provided specific guidance to the graduateteaching assistants regarding the grading of the final studentpresentations (Appendix A).

The marking rubric was carefully designed to emphasizethe importance of creativity and inquiry, as opposed to a nonselectivelisting of information. Students were informed wellin advance of their presentations that they would be markedfor their creativity and the quality of their presentation, aswell as for the scientific accuracy and completeness of information.As a result, students needed to master basic conceptsand apply them in a meaningful way to prepare a successfulpresentation.

References[BC31] Cited

Banaji MR, Greenwald AG. 2013. Blindspot: hidden biases of good people. New York: Random House.

Bednarski AE, Elgin SCR, Pakrasi HB. 2003. Aninquiry into protein structure and genetic disease: introducingundergraduates to bioinformatics in a large introductorycourse. Cell Biol Educ. 4:207-220.

Neumann M, Provart N. 2006. Using customized tools and databases for teaching bioinformatics in introductory biology courses. In: O'Donnell MA, editor. Tested studies for laboratory teaching. Volume 27. Proceedings of the 27th Workshop/Conference of the Association for Biology Laboratory Education (ABLE).p. 321-328.

Schneider TL, Linton BR. 2008. Introduction to protein structure through genetic diseases. J Chem Educ. 85(5):662-665.

Acknowledgments

Thank you very much to all of the BCEM 393 students and teaching assistants who have helped improve this laboratoryexercise over the last four years.

About the Authors

Author's name[LB32] has been an Instructor at the Universityof Calgary since 2006, where she teaches large coursesin genetics and biochemistry, primarily at the second-year[BC33]

Proceedings of the Association for Biology Laboratory Education, Volume 38, 20171

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Appendix A

Mission, Review Process & Disclaimer[BC34]

The Association for Biology Laboratory Education (ABLE) was founded in 1979 to promote information exchange among university and college educators actively concerned with teaching biology in a laboratory setting. The focus of ABLE is to improve the undergraduate biology laboratory experience by promoting the development and dissemination of interesting, innovative, and reliable laboratory exercises. For more information about ABLE, please visit

Papers published in Tested Studies for Laboratory Teaching: Peer-Reviewed Proceedings of the Conference of the Associationfor Biology Laboratory Education are evaluated and selected by a committee prior to presentation at the conference, peer-reviewedby participants at the conference, and edited by members of the ABLE Editorial Board.

Citing This Article

Author[BC35]. 2017. Title[BC36]. Article #[LB37]In: McMahon K, editor.Tested studies for laboratory teaching.Volume 38.Proceedings of the 38th Conference of the Association for Biology Laboratory Education (ABLE).

part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic,mechanical, photocopying, recording, or otherwise, without the prior written permission of the copyright owner.

ABLE strongly encourages individuals to use the exercises in this proceedings volume in their teaching program. If this exercise is used solely at one’s own institution with no intent for profit, it is excluded from the preceding copyright restriction, unless otherwise noted on the copyright notice of the individual chapter in this volume. Proper credit to this publication mustbe included in your laboratory outline for each use; a sample citation is given above.

Proceedings of the Association for Biology Laboratory Education, Volume 38, 20171

[BC1]Add text where appropriate, but do NOT change font styles, font sizes, or spacing. To preserve the template formatting, use Paste and Match Format in the EditMajor Workshoph and Lawrence S. BlumerWindows)1111111111111111111111111111111111111111111111111111111111111111111111111111111111 menu (Mac) or Paste Merge Formats in the Edit menu (Windows). Delete comments when a section is completed.

Save the file with the file name beginning with the last name of the first author. All uploaded files (manuscript, copyright, supplemental materials, poster, extended abstract) should have file names that start with the last name of the first author.

Your manuscripts file (using this template) should be named Last Name of AuthorMajor.docx for a major workshop, Last Name of AuthorMini.docx for a mini-workshop, or Last Name of AuthorPoster.docx for a poster.

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The Header will show the authors last names and the presentation type and running title on alternate pages from this page to the end.

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[BC20]Insert student outline. Student outline is single column and begins on a new page and ends on its own page.

The student outline shown here is an example, but is not intended to be prescriptive. Submit the student outline you would actually use with the laboratory activity you presented at the ABLE conference.

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[LB26]If there are cited references within the Student Outline, they should be listed here using Council of Science Editors format, name-year format.

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If subheadings are needed in this section, use the same format as shown on page 1 of this template.

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