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Using Undergraduate Molecular Biology Labs to Discover Targets of miRNAs in Humans

In this lesson, we describe an easily adaptable lab module that can be used in existing undergraduate molecular biology lab courses to conduct authentic scientific research, published in CourseSource

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Susan L Klinedinst onto Human Genetics

Using Bioinformatics to Understand Genetic Diseases: A Practical Guide

This Practical Guide outlines a number of basic bioinformatics approaches that can be used to understand the molecular basis of genetic diseases.

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Meiosis Remodeled: Inclusion of New Parts to Poppit Bead Models Enhances Understanding of Meiosis

A long-standing tradition uses strings of poppit beads of different colors to model meiosis, especially to show how segments of paired homologous chromosomes are recombined. Our use of orthodontic latex bands to model cohesion of sister chromatids, and plastic coffee stirrers as microtubules, extends what can normally be achieved with ‘standard’ commercial kits of beads, so emphasizing the importance of four key elements of meiosis: (a) the role of chromosome replication before meiosis itself begins; (b) pairing and exchange (chiasma formation) of homologous chromosomes during meiosis I; (c) centromere (kinetochore) attachment and orientation within/on the spindle during meiosis I and meiosis II; and (d) the differential loss of arm and centromere cohesion at onset of anaphase I and anaphase II. These are essential elements of meiosis that students best need to visualize, not just read and think about. Bead modeling leads them in that direction, as our gallery of figures and accompanying text show.

Primary image: Unassembled components of ‘PoppitMeiosis’ – a poppit bead exercise aimed at student learning of meiosis. Beads are snapped together to model bivalent chromosomes (on the right side), with double-stick tape (top) representing the synaptonemal complex, orthodontic latex bands representing cohesion rings, and coffee stirrers representing microtubule bundles that connect centromeres to the spindle poles.

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A Fun Introductory Command Line Lesson: Next Generation Sequencing Quality Analysis with Emoji!

Radical innovations in DNA sequencing technology over the past decade have created an increased need for computational bioinformatics analyses in the 21st century STEM workforce. Recent evidence however demonstrates that there are significant barriers to teaching these skills at the undergraduate level including lack of faculty training, lack of student interest in bioinformatics, lack of vetted teaching materials, and overly full curricula. To this end, the James Madison University, Center for Genome & Metagenome Studies (JMU CGEMS) and other PUI collaborators are devoted to developing and disseminating engaging bioinformatics teaching materials specifically designed for streamlined integration into general undergraduate biology curriculum. Here, we have developed and integrated a fun introductory level lesson to command line next generation sequencing (NGS) analysis into a large enrollment core biology course. This one-off activity takes a crucial but mundane aspect of NGS quality control (QC) analysis and incorporates the use of Emoji data outputs using the software FASTQE to pique student interest. This amusing command line analysis is subsequently paired with a more rigorous research-grade software package called FASTP in which students complete sequence QC and filtering using a few simple commands. Collectively, this short lesson provides novice-level faculty and students an engaging entry point to learning basic genomics command line programming skills as a gateway to more complex and elaborated applications of computational bioinformatics analyses.

Primary image: Undergraduate students learn the basics of command line NGS quality analysis using the FASTQE and FASTP programs.

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CRISPR Gene Editing: Designing the gRNA and Donor Template

In this adaptation, students learn how CRISPR/Cas9 is used in bacterial immunity and gene editing. Students create both a gRNA target and a donor template to edit a gene. Mutations can be from the case study, Piwi Matter, or designed by the instructor.

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Meiosis: A Play in Three Acts, Starring DNA Sequence

Meiosis is well known for being a sticky topic that appears repeatedly in biology curricula. We observe that a typical undergraduate biology major cannot correctly identify haploid and diploid cells or explain how and why chromosomes pair before segregation. We published an interactive modeling lesson with socks to represent chromosomes and demonstrated that it could improve student understanding of ploidy (1). Here we present an improvement on that lesson, using DNA paper strips in place of socks to better demonstrate how and why crossing over facilitates proper segregation. During the lesson, student volunteers act out the roles of chromosomes while the whole class discusses key aspects of the steps. Strips of paper with DNA sequences are used to demonstrate the degrees of similarity between sister chromatids and homologous chromosomes and to prompt students to realize how and why homologous pairing must occur before cell division. We include an activity on Holliday Junctions that can be used during the main lesson, skipped, or taught as a stand-alone lesson.

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Why do Some People Inherit a Predisposition to Cancer? A small group activity on cancer genetics

Before undergraduate students take a genetics course they generally know cancer has a genetic basis and involves the proliferation of cells; however, many are uncertain about why only a subset of people have a predisposition to cancer and how that predisposition is inherited from one generation to the next.  To help students learn about these concepts, we designed a teaching unit that centers on a small-group, in-class activity.  During this activity students learn how to:

  1. determine inheritance patterns for different types of cancer,
  2. explain why a person with or without cancer can pass on a genetic predisposition to cancer, and
  3. distinguish between proto-oncogenes and tumor suppressor genes. 

In addition to participating in the small-group activity, students watch short video clips from a documentary about breast cancer, answer clicker questions, and engage in a whole-class discussion.  A combination of pre/posttest results, clicker question answers, and performance on subsequent exam questions suggests that this unit helps students learn about the hereditary basis of cancer.

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Module 3: Transcription, Part II: What Happens to the Initial Transcript Made by RNA pol II?

This module teaches about the three key steps that are involved in converting the pre-mRNA into a mature mRNA: 1) The addition of a 5’ cap, 2) The addition of a 3’ poly(A) tail, 3) The removal of introns through splicing.

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Module 4: Removal of Introns from pre-mRNA by Splicing

In this module, students will learn to identify splice donor and acceptor sites that are best supported by RNA-Seq data, and use the canonical splice donor and splice acceptor sequences to identify intron-exon boundaries.

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Module 5: The Need for an Open Reading Frame

In this module, students will learn to identify the open reading frames for a given gene, and define the phases of the splice donor and acceptor sites.

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Maria vs Malaria

This case study focuses on a specific enzyme Lactate Dehydrogenase (LDH) in the malarial parasite as a target for treating malaria.

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Using computational molecular modeling software to demonstrate how DNA mutations cause phenotypes

Students require a deep understanding of the central dogma before they can understand complex topics such as evolution and biochemical disorders. However, getting undergraduate biology students to apply higher-order thinking skills to the central dogma is a challenge. Students remember and regurgitate the molecular details of transcription and translation but if asked to apply these details, such as how a DNA mutation might affect phenotype, it becomes clear that most students do not deeply understand the central dogma. This lesson is a five-week series of laboratory activities designed to help students transition from applying lower order thinking skills to the central dogma to applying higher-order thinking skills. Over five weeks, students explore the phenotype of Arabidopsis asymmetric leaves 1 (as1) and as2 mutants. Students isolate DNA from wild-type and mutant plants and determine the sequence of the AS1 and AS2 alleles. Students use the DNA sequence data to determine the mutant protein amino acid sequences. They submit the mutant and wild-type protein sequences to a free online server and obtain three-dimensional (3-D) models of the wild-type and mutant proteins. They use free software to analyze and compare the 3-D models to determine the structural differences between the wild-type and mutant proteins. These computer-generated models can be 3-D printed allowing students to better visualize the protein structure. The overall goal is to use student-centered laboratory activities to demonstrate the relationship between DNA sequence, protein structure/function, and phenotype.

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Module 1: Introduction to the Genome Browser: What is a Gene?

This lesson introduces the University of California Santa Cruz genome browser to students, walking them through some of the key features so that it can be used for analysis of gene structure.

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Module 6: Alternative Splicing

This module explores how multiple different mRNAs and polypeptides can be encoded by the same gene. After completing this module students will be able to explain how alternative splicing of a gene can lead to different mRNAs.

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Why Meiosis Matters: The case of the fatherless snake

A compelling reason to learn something can make all the difference in students’ motivation to learn it.  Motivation, in turn, is one of the key attitudes that drives learning.  This story presents students with a compelling puzzle of a fatherless snake.  The puzzle motivates students to learn about meiosis and mitosis, since the only way to explain the origin of the fatherless baby is by mastering details of meiosis.  During the process, students work through the major steps in meiosis, compare and contrast mitosis and meiosis, and apply their understanding to predict how meiosis “went wrong” to produce an unusual offspring that did not originate through union of an egg and a sperm.  This story can be adapted for introductory or advanced students and can be scaled from a brief introduction in a single lecture to a series of active learning exercises that could take two or more lecture periods.

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A CURE-based approach to teaching genomics using mitochondrial genomes

There is an abundance (currently over 1016 DNA bases) of publicly available genetic sequence data and a dearth of trained genomicists to process and interpret it, necessitating more trained bioinformaticians with biological expertise. For example, thousands of data sets are deposited on NCBI's Sequence Read Archive with plans to use only part of the data generated, though much of this data could be used to address other important biological questions. Course-Based Undergraduate Research Experiences (CUREs) are growing in popularity as a way to engage undergraduates in a project-based learning experience to analyze data that could not otherwise be processed. Through CUREs, students can receive training in the most relevant and up-to-date skill sets used within the field. We present a lesson plan for a CURE centered around teaching genome annotation. This project is suitable as a four week module in an undergraduate/graduate cross-listed course and focuses on annotating streamlined organellar genomes. This module is similar to other programs, such as the Genomics Education Partnership. However, students are additionally provided with the opportunity to publish their annotated genomes to NCBI's GenBank. In addition, many students who have taken this course have gone on to pursue internships and careers using the bioinformatics skills gained.

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CURESUB Lecture 5 - OMICS

s assistant professor in the department of medicine at Rutgers Robert Wood Johnson Medical School, Manisha Bajpai, PhD., led the Gastroenterology division’s clinical and translational research efforts funded by the NIH/NIDDK and grants from industry foundations. Her research initiative focused on early-stage biomarker discovery in Barrett’s esophagus and Inflammatory Bowel Diseases using various contemporary molecular biology, cell biology as well as Omics methods. In this lecture we will develop a basic understanding of the methods of the various ‘omics” approaches and discuss their potential in improving human health.

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Should we synthesize a human genome?

Two articles introducing the Human Genome Project-Write and asking questions about the ethics of the project.

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Pedigree Unspoken Assumptions

A video that highlights the unspoken assumptions that we use in pedigree analysis.

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An undergraduate bioinformatics curriculum that teaches eukaryotic gene structure

Gene structure, transcription, translation, and alternative splicing are challenging concepts for many undergraduates studying biology. These topics are typically covered in a traditional lecture environment, but students often fail to master and retain these concepts. To address this problem we have designed a series of six Modules that employ an active learning approach using a bioinformatics tool, the genome browser, to help students understand eukaryotic gene structure and functionality. Students learn how to use a mirror site of the UCSC Genome Browser created by the Genomics Education Partnership while completing the Modules, which focus on gene structure, transcription, splicing, translation, and alternative splicing. The Modules are supplemented with short videos that illustrate key functionalities of the genome browser and fundamental concepts in processing transcripts. These materials have been used successfully to teach gene structure in many different settings, from community colleges to 4-year colleges and universities, encompassing advanced high school students to college seniors. Instructors can easily customize the Modules and/or select a subset for their curriculum. The Modules have helped our students learn about eukaryotic gene structure and expression, simultaneously acquiring skills in the use of a genome browser, and have prepared them to pursue genome annotation projects as independent research.

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Splicing it Together: Using Primary Data to Explore RNA Splicing and Gene Expression in Large-Lecture Introductory Biology

At the heart of scientific ways of knowing is the systematic collection and analysis of data, which is then used to propose an explanation of how the world works. In this two-day module, students in a large-lecture course are immersed in a biological problem related to the Central Dogma and gene expression. Specifically, students interpret experimental data in small groups, and then use those data to craft a scientific argument to explain how alternative splicing of a transcription factor gene may contribute to human cancer. Prior to the module, students are assigned a reading and provided PowerPoint slides outlining the basics of alternative splicing and refreshing their understanding of gene regulation. Students complete a pre-class assignment designed to reinforce basic terminology and prepare them for interpreting scientific models. Each day of the module, students are presented experimental data or biological models which they interpret in small groups, use to vote for viable hypotheses using clickers, and ultimately leverage in a culminating summary writing task requiring them to craft a data-driven answer to the biological problem. Despite the novelty of the argumentation module, students engage in all aspects (inside and outside of the classroom) of the activity and are connected across data, hypotheses, and course concepts to explain the role of alternative splicing in gene expression and cancer.

Primary image: Splicing it together. Students work together, interpreting primary data and models to investigate the effects alternative splicing may have on gene regulation and cancer.

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Splicing it Together: Using Primary Data to Explore RNA Splicing and Gene Expression in Large-Lecture Introductory Biology

At the heart of scientific ways of knowing is the systematic collection and analysis of data, which is then used to propose an explanation of how the world works. In this two-day module, students in a large-lecture course are immersed in a biological problem related to the Central Dogma and gene expression. Specifically, students interpret experimental data in small groups, and then use those data to craft a scientific argument to explain how alternative splicing of a transcription factor gene may contribute to human cancer. Prior to the module, students are assigned a reading and provided PowerPoint slides outlining the basics of alternative splicing and refreshing their understanding of gene regulation. Students complete a pre-class assignment designed to reinforce basic terminology and prepare them for interpreting scientific models. Each day of the module, students are presented experimental data or biological models which they interpret in small groups, use to vote for viable hypotheses using clickers, and ultimately leverage in a culminating summary writing task requiring them to craft a data-driven answer to the biological problem. Despite the novelty of the argumentation module, students engage in all aspects (inside and outside of the classroom) of the activity and are connected across data, hypotheses, and course concepts to explain the role of alternative splicing in gene expression and cancer.

Primary image: Splicing it together. Students work together, interpreting primary data and models to investigate the effects alternative splicing may have on gene regulation and cancer.

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Targeting Misconceptions in the Central Dogma by Examining Viral Infection

Understanding the central dogma and how changes in gene expression can impact cell function requires integration of several topics in molecular biology. Students often do not make the necessary connections between DNA structure, transcription, translation and how these processes work together to impact cell function. This lesson seeks to tie together these concepts through the use of data from primary literature, in the context of viral infection. This lesson asks students to think like scientists as they design experiments, make predictions and interpret and evaluate data from primary literature on how changes in the expression of a glucose transporter gene can alter the function of a cell through changes to glucose uptake and metabolism. This lesson incorporates the Vision and Change core concept of information flow and the core competency of quantitative reasoning. It also addresses The Genetics Society of America learning framework goal of Gene Expression and Regulation (How can gene activity be altered in the absence of DNA changes?). This lesson was taught in three sections of a small-enrollment undergraduate class and assessed summatively using a pre/post test and formatively using in class via personal response systems. This lesson describes the design, implementation and results of student assessment, and offers suggestions on how to adapt the materials to a variety of contexts including different class sizes, different units of introductory biology, and upper-level classes.

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More Mice with Fangs: Intermediate Punnett Squares

An online module utilizing probability and Punnett squares to introduce students to more complex genetic problems. The module emphasizes students' use of probability to solve the problems.

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How to Find a Gene: Retrieving Information From Gene Databases

A strong understanding of distinct gene components and the ability to retrieve relevant information from gene databases are necessary to answer a diverse set of biological questions. However, often there is a considerable gap between students’ theoretical understanding of gene structure and applying that knowledge to design laboratory experiments. In order to bridge that gap, our lesson focuses on how to take advantage of readily available gene databases, after providing students with a strong foundation in the central dogma and gene structure. Our instructor-led group activity aids students in navigating the gene databases on their own, which enables them to design experiments and predict their outcomes. While our class focuses on cardiomyocyte differentiation, classes with a different focus can easily adapt our lesson, which can be conducted within a single class period. Our lesson elicits high engagement and learning outcomes from students, who gain a deeper understanding of the central dogma and apply that knowledge to studying gene functions.

Primary Image: Gene structure at various levels of expression and retrieval of corresponding biological information from gene databases. This image contains a screenshot from the NCBI Database, which is an open source: National Center for Biotechnology Information. 2021. SOX2 SRY-box transcription factor 2.

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