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Using Open-Source Bioinformatics and Visualization Tools to Explore the Structure and Function of SARS-CoV-2 Spike Protein

The relationship between protein structure and function is a foundational concept in undergraduate biochemistry. We find this theme is best presented with assignments that encourage exploration and analysis. Here, we share a series of four assignments that use open-source, online molecular visualization and bioinformatics tools to examine the interaction between the SARS-CoV-2 spike protein and the ACE2 receptor. The interaction between these two proteins initiates SARS-CoV-2 infection of human host cells and is the cause of COVID-19. In assignment I, students identify sequences with homology to the SARS-CoV-2 spike protein and use them to build a primary sequence alignment. Students make connections to a linked primary research article as an example of how scientists use molecular and phylogenetic analysis to explore the origins of a novel virus. Assignments II through IV teach students to use an online molecular visualization tool for analysis of secondary, tertiary, and quaternary structure. Emphasis is placed on identification of noncovalent interactions that stabilize the SARS-CoV-2 spike protein and mediate its interaction with ACE2. We assigned this project to upper-level undergraduate biochemistry students at a public university and liberal arts college. Students in our courses completed the project as individual homework assignments. However, we can easily envision implementation of this project during multiple in-class sessions or in a biochemistry laboratory using in-person or remote learning. We share this project as a resource for instructors who aim to teach protein structure and function using inquiry-based molecular visualization activities.

Primary image: Exploration of SARS-CoV-2 spike protein: student generated data from assignments I - IV. Includes examples of figures submitted by students, including a sequence alignment and representations of 3D protein structure generated using UCSF Chimera. The primary image includes student generated data and a cartoon from Pixabay, an online repository of copyright free art. 

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Erin Weber onto Biochem

When tests disagree, how do I know if I have COVID-19?

Students will learn about infectious disease and the immune response to infection by investigating different types of tests (PCR, antigen, and antibody tests) to detect the SARS-CoV-2 viral genetic material, antigens, or anti-SARS-CoV-2 antibodies. In the activity, students will apply core concepts and competencies from Vision & Change (https://visionandchange.org/). The activity uses a jigsaw format, with students choosing one of three specialities (epidemiologist, infectious disease doctor, or immunologist) and completing an assignment, either in-class or as homework, based on their speciality. In groups, students first hold a conference by speciality, then teams with representatives from each speciality discuss possible conclusions using results from the three different tests for a hypothetical patient.

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Sumali Pandey onto ImmunoReach Teaching Resources

Molecular CaseNet Biweekly meeting related (Feb. 3, 2023)

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Shuchismita Dutta onto Meeting Recordings

Celebrating Black History Month

Pat shared this link

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Shuchismita Dutta onto Scientist Spotlight related

A Kinesthetic Modeling Activity to Teach PCR Fundamentals

Most molecular biology and biological sciences students understand that the polymerase chain reaction (PCR) is used to amplify DNA. However, we have found that some students experience conceptual misunderstandings, a lack of detailed comprehension of the PCR process, or difficulties with troubleshooting and predicting the effects of alterations to the standard PCR process. We hypothesized that a problem-based learning approach that incorporates a kinesthetic modeling of the PCR process could address these problems. During this hands-on learning activity, students “amplified” a specific region of template DNA through three cycles of PCR using a “toolkit” composed of a) intertwined, supercoiled, and double-stranded yarn representing template DNA, b) short wax sticks representing primers, and c) long wax sticks representing the PCR products. Instructors can introduce a variety of assessments, including real-time image capture of the models, pre- and post-activity assessment quizzes, and homework assignment to gauge student learning. We administered identical four-question quizzes worth 12 points to 28 undergraduate students before and after the activity. The mean score on the post-quiz was three points higher than the pre-quiz score, demonstrating a 75% increase in score. Moreover, we found that students who began the activity with lower levels of understanding experienced the most significant learning gains. This hands-on, student-centered, kinesthetic activity allowed students to (i) visualize PCR processes, (ii) construct a model of the PCR process, (iii) correct common misconceptions and sources of confusion, and (iv) actively engage in the learning process.

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Michael Moore onto 2171 Ideas

Mapping a Mutation to its Gene: The "Fly Lab" as a Modern Research Experience

Although genetics is an invaluable part of the undergraduate biology curriculum, it can be intimidating to students as well as instructors: Students must reduce their reliance on memorization and dive deep into quantitative analysis, and instructors must make a long, rich history of genetics experiments clear, coherent, and relevant for students. Our Lesson addresses these challenges by having students map an unknown mutation to its gene using a modern suite of genetic tools. Students receive a Drosophila melanogaster strain with a mutation that causes the normally flat wing to bend at distinct sites along its length. Although we recently mapped this mutation to its gene, here we have renamed it "crumpled wing" (cw), an example of a pseudonym that you could use in the classroom. Like many standard "fly labs" that are taught at undergraduate institutions, this Lesson reinforces classic genetics concepts: students selectively mate fly strains to determine mode of inheritance, test Mendel's Laws, and three-point map an unknown mutation relative to known markers. But here, we expand on this tradition to simulate a more modern primary research experience: we greatly increase mapping resolution with molecularly-defined transgene insertions, deletions, and duplications; then cross-examine our data with key bioinformatic resources to identify a short-list of candidate cw genes. After extensive data interpretation and integration, students have been able to map cw to a single gene. This Lesson has a flexible design to accommodate a wide range of course structures, staffing, budgets, facilities, and student experience levels.

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A Rapid Genetic Screen Using Wisconsin Fast Plants<sup>®</sup>: A Hands-On Approach to Inheritance of <i>de novo</i> Mutations

Some concepts in genetics, such as genetic screens, are complex for students to visualize in a classroom and can be cumbersome to undertake in the laboratory. Typically, very large populations are needed, which can be addressed by using micro-organisms. However, students can struggle with phenotyping microbes. For macroscopic organisms, the number of offspring produced, and the generation time can be challenging. I developed this lesson as a small-scale genetic screen of Fast Plants®. These plants are amenable to teaching labs as they have simple growth requirements, a short generation time, and produce numerous seeds that can be stored for years. Seeds used for this screen are purchased pre-treated with a DNA damaging agent, removing the need for in-house use of mutagens. Also, students can screen the phenotypes without specialized equipment. The initial lesson begins with an examination of the first generation of plants. Later their offspring are screened for altered phenotypes. Students responded well to having full-grown plants available on the first day of the lab project. This lesson fostered student collaboration, as they worked with class datasets. Differences in growth due to mutagenesis treatment in the first generation were clear to students who had not worked with plants before. Identifying plants with altered phenotypes in the next generation was more of a challenge. This lesson incorporates key concepts such as somatic and germline mutations, the impact of such mutations on phenotype, and the inheritance of mutation alleles, and provides a hands-on way to illustrate these concepts.

Primary Image: Fast Plant® phenotype differences observed in the M2 generation. This pot contains three full-sibling M2 seedlings from a single M1 parent plant. The seed of their parent plant received 50 Krads of radiation. Plants 1 and 2 are of standard height, while plant 3 is greatly elongated. Image by AL Klocko.

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Michael Moore onto 2171 Ideas

Developing Data Literacy Skills and Connecting the Student Experience in the Classroom to the Community Through Biodiversity Projects

Undergraduate education and long-term science literacy are enhanced by integrating data projects with public datasets and creating analysis summaries. Underutilized public datasets are often generated by community-based or citizen science projects to address conservation issues supported by local residents. The objectives of this course activity are for students to contribute to a community science project, observe local species diversity, develop biodiversity questions, and apply data science techniques. Engaging students in these local projects enhances their understanding of the scientific process and its broader impacts on their community. The City Nature Challenge (CNC) is an annual global community science event where students participate by documenting species observations with the iNaturalist application, similar to localized BioBlitz events. Students are guided through using the iNaturalist database to practice biodiversity calculations then data is collected through participation in CNC (or a BioBlitz event an instructor arranges for their class). Spreadsheet software is used by students to organize, analyze, and summarize their relevant data to their peers. Students join the iNaturalist community of observers, which includes professional and non-professional naturalists. Therefore, students can see the themselves as scientists by contributing locally relevant data to a global and digital community of scientists. Experience working with large datasets such as the CNC iNaturalist dataset is essential for STEM careers and building data literacy. Implementing these experiences in classrooms will provide students unique opportunities to learn more about local biodiversity, develop interdisciplinary skills and positively influence a global network of scientists.

Primary image: Students recording biodiversity observations in an open field. At the annual Macaulay Honors College BioBlitz, students are divided into teams to explore a specific NYC park and record the animal and plant life they observed, which they later used to generate biodiversity reports including the species richness and abundances for the park.

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Erika Crispo onto BEDE

Three Research-Based Quantitative Reasoning Modules for Introductory Organismal Biology Laboratories

We have designed three laboratory modules for an introductory organismal biology course with an emphasis on quantitative reasoning and data analysis skills. Module 1 tests for dimorphism in crayfish chelae using a paired statistical design. Module 2 tests for allometric growth of tapeworm hook structures using a regression model. Module 3 tests for differences in stomatal densities between two groups of plants using a two-sample statistical approach. For all three modules, we emphasize the use of confidence intervals to draw statistical conclusions about hypotheses. Knowledge about the basic biology of animals and plants is required, including arthropods, platyhelminths, and vascular plants. Background reading on dimorphism, allometry, and transpiration provides the necessary foundation to develop questions and hypotheses. Some familiarity with R is necessary for both students and instructors, although the activities can be modified for analysis with Excel or another statistical package. These modules can be taught independently or together as a unit within a course. As stated in the AAAS document, Vision and Change: A Call to Action, the ability to use quantitative reasoning is a core competency that must be developed by all biology students. These modules address the call for instruction in quantitative reasoning and provide a hands-on active introduction to key tools that will be required to build students’ statistical repertoire in more advanced courses.

Primary Image: A highlight of the three modules used in our introductory organismal biology course, including the use of calipers to test for dimorphism in the size of crayfish chelae (upper right), a leaf impression (lower right) from a hydrangea plant (lower left) used to test hypotheses about stomata densities, and the image of an Echinococcus tapeworm (upper left) to test hypotheses about allometry.  

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Erika Crispo onto BEDE

Quantifying and Visualizing Campus Tree Phenology

Cards to include on website

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Modeling the Research Process: Authentic human physiology research in a large non-majors course

Laboratory experiences in large-enrollment introductory science courses often utilize “cookie-cutter style” laboratory experiences due to the relative simplicity of setting up the lab stations, as well as a need to teach students particular course content. These experiences rarely offer insights into the way science is done in the research setting, resulting in a lack of understanding of the scientific process. In addition, students enrolled in non-majors introductory science courses often fail to see the relevance between what they are doing in the lab and what they are learning in the lecture portion of their course. To address this gap, we developed a laboratory module for a non-majors Human Biology course that provides students with a hands-on, authentic research experience using the iWorx software and hardware for human physiology. Weekly modules were designed to guide students through the major steps of the research process, including reading current scientific literature, developing a testable hypothesis, designing and performing a physiology experiment, analyzing data and presenting their findings to their peers. The described course framework encouraged students to participate in the scientific process, providing them with the opportunity to engage in an authentic research experience. The model described here could be adapted for use with introductory or advanced students, and could be modified to fit any research model available to the instructor. Utilizing the multi-week format described is recommended for students to gain the full benefit from the research-design-revise process.

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Benjamin Wilhelm onto A&P

What do Bone and Silly Putty® have in Common?: A Lesson on Bone Viscoelasticity

Without the use of real-life examples and models, actively instructing and engaging students in complex physiology topics related to bone biomechanics can be challenging. In our large-enrollment Human Physiology & Anatomy courses at the University of Connecticut, the skeletal system is the first organ system that we cover in depth, rendering even more important our establishment of (and emphasis on) how fascinating--and directly applicable to everyday life--the anatomical features and physiological properties of organs can be. Because our lecture courses are supplemented with 2 hours per week of anatomy-intensive laboratory investigations, we tend to focus heavily on physiology concepts during lecture. For the skeletal system, we consider stress-strain curves in the context of bone biomechanics, including the materials-science concepts of elasticity, plasticity, and viscoelasticity, and the more generalizable concepts of hysteresis and anisotropy. Hoping to provide a fun, entertaining, and real-world perspective on these topics, we used Silly Putty® as an inexpensive, familiar, and readily-available model of some of these bone properties. This lesson allows students to get engaged in, and familiarized with, biomechanical concepts through demonstration of this well-known play material's properties, as a concrete reference point. Coupling the lesson with active questioning and think-pair-share activities allows students to develop skills in data interpretation and to apply previously-acquired knowledge bases to a novel situation. In this lesson, we provide instructors with a template for re-creating this demonstration, which can be accompanied by active-learning strategies and resources that promote development of data-interpretation and problem-solving skills in students.

This article has an accompanying Science Behind the Lesson article: "A Short Bone Biomechanics Primer: Background for a Lesson on Bone Viscoelasticity."

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Benjamin Wilhelm onto A&P

To Vaccinate or Not to Vaccinate

To vaccinate or not to vaccinate, that is the question. Much of the recent trend in society against vaccination is that the general population does not understand 1) how vaccines work and 2) how one's vaccination status can influence others. Further compounding this is rather low acceptance of the influenza vaccine, a vaccine which is sometimes not even effective against the strains predominantly in circulation. Through engaging in a conversation about the role of vaccines in immunity not only of oneself but also about surrounding persons, we can increase vaccine acceptance. Herein is a physical assay which illustrates the concept of herd immunity with differing levels of vaccinations within a population. Students will learn that low vaccination rates do little to nothing to stop disease spread and that a large portion of the population (80%) is necessary to achieve near-eradication. This lesson is able to be taught at multiple levels using supplies that can mostly be obtained at the grocery store. In addition to illustrating vaccination, this study approximates a direct enzyme-linked immunosorbent assay (ELISA), enabling students to better understand that technique and how it is used to diagnose disease as well as the interrelation between antigens and antibodies.

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Benjamin Wilhelm onto Mammalian Physiology

Understanding Gastric Acid Secretion: An Active Learning Approach

The human digestive system is a diverse network of cells, tissues, and organs that is regulated by systemic (e.g., nervous and endocrine systems) and local factors (e.g., secretions, pH, and the microbiome). Given the volume of content and the dense physiology involved, this system is difficult for instructors to teach and equally challenging for students to understand. This is especially true in our two-semester Human Anatomy and Physiology course for pre-health students at the University of Connecticut. In the Spring 2017 semester, we developed and implemented an active-learning based approach when teaching the histology and regulation of gastric secretions—a physiology-intensive topic within the digestive system unit. Our lesson included a team-based case study on gastric ulcer formation and Helicobacter pylori, a guided drawing depicting the molecular mechanisms of HCl secretion, a concept map linking the cells with their secretions, a think-pair-share on pharmacological regulators, and a reflective assignment placing the content within a broader societal context. Consistent with the themes of active learning, the lesson is suitable for any physiology instructor seeking to create a more engaging classroom, and provide students with opportunities to problem solve, think critically, and build relationships between course content and real life.

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Benjamin Wilhelm onto Mammalian Physiology

A Quick and Simple Natural Selection Role Play

Teaching evolution remains a challenging task in biology education. Students enter the classroom with stubborn misconceptions and many traditional examples of the process of evolution may not resonate with students. This short role play activity is designed to easily integrate into any class session on evolution and provide students with a concrete, tangible example of natural selection. In addition, it specifically addresses several misconceptions about evolution. In this activity, students become a fictional population that is under a selection pressure. As students take on the role of a population, they are reminded of the requirements for natural selection, fall victim to a selection pressure, and observe the change in allele frequencies over time. In the context of a class session that focuses on the mechanisms of evolution, students are able to immediately visualize the process of natural selection. This role play only takes 10-15 minutes, requiring minimal class and preparation time. It has been successfully used in both introductory and non-majors' biology classrooms. Though simplified and fictional, this role play provides a concrete example as a foundation for students' growing understanding of evolution.

Primary image: Depicts visual representation of populations evolving.

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Benjamin Wilhelm onto BIOL 1004

One species, two species, red species, lead species? Phylogenetics and species concepts with Plethodon salamanders

This lab introduces students to species concepts and basic computer-based tree-building methods using published nuclear and mitochondrial sequence data for Plethodon salamanders.

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Katie M. Sandlin onto Bioinformatics

Yeti or not: Do they exist?

Through this 4-part bioinformatics case study, students will be led through the forensic analysis of putative Yeti artifacts based on published findings.

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Katie M. Sandlin onto Bioinformatics

Biodiversity Show and Tell: An Accessible Activity to Encourage Students to Explore the Tree of Life

An appreciation of organismal diversity is a requirement for understanding evolution and ecology, and can serve as a source of amazement and wonder that inspires students to enjoy biology. However, biodiversity can be a challenging subject to teach: it often turns into a procession of facts to memorize and a disorienting list of Latin names. To help engage students in this topic, we developed an activity in which each student contributes to a class "biodiversity tour" of strange and intriguing species. Students in our large-enrollment introductory biology course use the Internet to find a species that interests them and that they think will interest their peers. They research their species and complete a worksheet to report their findings. Then they meet in discussion sections of ~32 students (in person or online) where each student gives a brief presentation about their species using a slide they have prepared, producing a lively, crowd-sourced, rapid-fire nature documentary. The performance for their peers motivates students to find the strangest species possible. Students overwhelmingly reported that this activity taught them something new about life on Earth and increased their interest in our planet's species. Many students also reported that this activity caused them to talk to someone about biology outside of the class and increased their personal connection to the natural world, suggesting that it helped them see the relevance of biology to their everyday lives. This simple activity can enrich an introductory biology course of almost any size.

Primary image: Photos of some of the species chosen by students in Fall 2019.

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Sarah MacLean onto Bio 1

Escape Zoom!: Reviewing Introductory Evolution Content Using an Escape Room Format

Reviewing and integrating key concepts and learning goals at the end of a biology course can be overwhelming to students and instructors alike. Often end-of-term review sessions in preparation for final exams are heavily based on memorization, and content coverage may be favored over students’ deeper understanding of fewer key ideas. We developed a final exam review for a virtual introductory evolution course using an “escape room” format, which consisted of unique activities—including puzzles, role-playing, and literature searches—aligned with course learning goals. Similar to a traditional escape room, students needed to collaboratively solve or complete each activity before moving on to the subsequent task. Our escape room activity was conducted virtually via Zoom and included both whole-class and smaller breakout room interactions. We recommend instructors utilize escape rooms as an engaging and effective way to review key concepts in their courses.

Primary image: Virtual Escape Room. In our activity, students virtually engage in activities related to evolutionary topics such as cichlid speciation, mRNA COVID-19 vaccines, and extinction, among others. All images used in this image are open source, and associated links for all images are listed here: https://unsplash.com/photos/smgTvepind4, https://unsplash.com/photos/4_hFxTsmaO4, https://unsplash.com/photos/_BJVJ4WcV1M, https://unsplash.com/photos/k0KRNtqcjfw, https://unsplash.com/photos/Pitb97HIn6Y

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Tamara Johnstone-Yellin onto Evolution

Interactive Video Vignettes (IVVs) to Help Students Learn Genetics Concepts

Many video resources exist to teach Mendelian genetics, but most consist of passive delivery of information rather than active construction of knowledge by users. We have created two interactive video vignettes (IVVs) that can be used together or separately to introduce students to core concepts of genetics, using principles of active learning (e.g., elicit-confront-resolve, directed feedback, reflection). These online resources are free and can be assigned as homework for students to complete outside of class. Each IVV features a realistic scenario of undergraduate students investigating genetic phenomena by collecting and analyzing data. During the IVVs, the user is integrated into the process, answers conceptual questions, receives feedback based on their answers, and reflects on the experience by comparing their original ideas to their new understandings. Marfamily is primarily designed to teach pedigree construction and analysis, while A Matter of Taste addresses common misconceptions about dominance. Both also demonstrate the scientific method. Users cannot advance without answering the questions, although they can review past scenes. Resources for both formative and summative assessment are provided. The IVV is easily integrated into any course where an introduction to or review of basic genetics is needed.

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Steven Krawczyk onto Genetics

BioVEDA Curriculum: An Approach to Link Conceptual and Quantitative Understanding of Variation During Experimental Design and Data Analysis

When performing a biological investigation, experts constantly cycle between conceptual and quantitative modes of thinking, integrating their understanding in both worlds to make decisions about their work. This cycling and mixing of conceptual and quantitative thinking in biology can be difficult for students. One way to help students integrate conceptual and quantitative thinking is by focusing on a single topic that has both conceptual and quantitative aspects. We have designed a curriculum that focuses on variation in experimental design and data analysis (The Biological Variation in Experimental Design and Analysis [BioVEDA] curriculum). We chose to focus on the idea of variation because it must be understood both conceptually and quantitatively at many points throughout a biological investigation. Additionally, this ability to apply quantitative thinking to biological concepts has been prioritized in national undergraduate education policy documents. Our curriculum consists of five activities that ask students to explore the idea of variation during the design of an experiment, and the representation and analysis of data. The activities are based on worksheets and incorporate Think-Pair-Share techniques with discussions facilitated by the instructor. We have implemented this curriculum twice in an introductory biology laboratory class for undergraduate students that is taught by graduate teaching assistants (TAs). So far, we have found that both TAs and students benefit from working through this curriculum. Students significantly improved in their understanding of variation in the context of biological investigations, and TAs gained more confidence in their ability to teach this content using active-learning techniques.

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Anne Cross onto Ecology Class

Molecular CaseNet Biweekly meeting related (Jan. 6, 2022)

Shuchi shares the Molecular CaseNet pipeline

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