Advanced - Using Bioinformatics: Genetic Research

Bio-ITEST logoThis is the second of a two-part series in NWABR's bioinformatics curriculum, funded by a grant called Bio-ITEST. ITEST grants are for Innovative Technology Experiences for Students and Teachers, from the National Science Foundation (NSF). This three-year grant provides funding for education outreach programs that help secondary school teachers and their students learn about how information technology is used in biological research.

Major collaborators include Digital World Biology, EdLab Group, and Shoreline Community College. The program also draws on NWABR’s strong relationships with school districts, community groups, bioethicists and NWABR member research institutions.

This curriculum unit explores how bioinformatics is used to perform genetic research. Specifically, the bioinformatics tools of BLAST, ORFinder, ClustalW and Cn3D are used to analyze genetic sequences.

The cytochrome c oxidase subunit 1 (COI) gene is introduced as the “DNA barcoding” gene that allows for identification of animal species. Students examine DNA sequences from different animal species, investigate the relationship between protein structure and function, and explore evolutionary relationships among eukaryotic organisms.

The unit concludes with an authentic student research project, sequencing the COI genes from samples obtained through a partnership with the Seattle Aquarium in Seattle, Washington, or samples they collect themselves in the community.

Throughout the unit, students are presented with a number of career options in which the tools of bioinformatics are developed or used.  The career lesson near the end of the unit culminates with resume and cover letter writing activities and a mock job interview.

Download the full Overview Unit Plan including correlation to National Science Standards and the Next Generation Science Standards.

Lesson One -- The Process of Genetic Research
PowerPoint for Lesson One

In this lesson, students are introduced to the process of genetic research. The lesson begins with a Think-Pair-Share activity designed to introduce students to the types of research questions people in different career fields might answer using bioinformatics tools. After a short background explanation provided by the teacher about how genetic research is done, students make their own hypotheses or predictions about the relatedness of canine species, and align paper DNA sequences to evaluate their hypotheses. The lesson concludes with a group activity introducing students to pairwise comparisons of DNA sequences, which will be explored more fully in later lessons.

Lesson Two -- DNA Barcoding and the Barcode of Life Database
PowerPoint for Lesson Two

In this lesson, students will receive an "unknown" DNA sequence and use the bioinformatics tool Basic Local Alignment Search Tool (BLAST) to identify the species from which the sequence came. Students then visit the Barcode of Life Database (BOLD) to obtain taxonomic information about their species and form taxonomic groups for scientific collaboration. The lesson ends with students generating a hypothesis based on the species within each group.

Lesson Three -- Using Bioinformatics to Study Evolutionary Relationships
PowerPoint for Lesson Three

Students learn how to use bioinformatics tools to analyze DNA sequence data and make conclusions about evolutionary relationships. Students collaborate with their group members by pooling their DNA sequences from Lesson Two: DNA Barcoding and the Barcode of Life Database (BOLD) to perform and analyze multiple sequence alignments using the computer programs ClustalW2 and JalView. After comparing relatedness among and between the species within their group, students use their sequence alignment to generate a phylogenetic tree, which is a graphical representation of inferred evolutionary relationships. This tree is used to draw conclusions about their research question and hypothesis.

Lesson Four -- Using Bioinformatics to Analyze Protein Sequences
PowerPoint for Lesson Four

Students perform a paper exercise designed to reinforce the concepts of the complementary nature of DNA and how that complementarity leads to six potential protein reading frames in any given DNA sequence. They will also gain familiarity with the circular format codon table. Students then use the bioinformatics tool ORFinder to identify the reading frames in their DNA sequence from Lesson Two and Lesson Three, and to select the proper open reading frame to use in a multiple sequence alignment using their protein sequences.

Lesson Five -- Protein Structure Dictates Function:  A Molecular Murder Mystery
PowerPoint for Lesson Five

Prior to this lesson, students learned how the cytochrome c oxidase gene is used in barcoding organisms. In this lesson, students learn more about the cytochrome c oxidase protein and its three dimensional structure. In particular, students learn how to identify the active site in cytochrome c oxidase. Once they can find this site, they look at aligned structures (one of which contains a poison) and then identify the poison. This lesson allows students to explore the use of the molecular visualization software Cn3D to learn more about cytochrome c oxidase, a ubiquitous and important protein.

Lesson Six -- Assessment:  Writing Research Reports
PowerPoint for Lesson Six

In this lesson, students compile and synthesize what they have learned in the preceding lessons by writing a research report. The research report includes Introduction, Methods, Results, Discussion, and References sections. Emphasis is placed on relating previous lesson activities to the original research question and hypothesis. Extensions and lesson alternatives include instructions for creating a scientific poster and writing an abstract.

Lesson Seven -- Who Should Pay?  Funding Research into Rare Genetic Diseases
PowerPoint for Lesson Seven

Students learn about Leigh’s disease, a rare form of Subacute Necrotizing Encephalomyelopathy (SNEM) that can be caused by a deficiency in cytochrome c oxidase (complex IV). Deficiencies in the large, 13-subunit cytochrome c oxidase complex can result from mutations in several genes including the barcoding gene, COI. Without the COI protein, cells are unable harness usable energy from glucose. This is a jigsaw exercise. Students are assigned or choose one of four stakeholder parties. They meet in ‘like’ interest groups to become more familiar with that person’s position and concerns. Afterwards, they meet in ‘mixed’ groups with a representative from each of the stakeholder groups. Students identify areas of agreement and disagreement, and propose a compromise to recommend to Congress regarding funding for rare disease research.

Lesson Eight -- Exploring Bioinformatics Careers
PowerPoint for Lesson Eight

Students synthesize the information they have learned throughout the unit about people in various careers who use bioinformatics. Students then have the opportunity to perform independent research about a career of interest before developing a resume to use when applying for a bioinformatics-related job. Students then learn about writing cover letters. Optional extensions include peer-editing of resumes and a mock interview for jobs related to a career that interests them.

Lesson Nine -- Analyzing DNA Sequences
PowerPoint for Lesson Nine

DNA sequencing is performed by scientists in many different fields of biology. Many bioinformatics programs are used during the process of analyzing DNA sequences. In this lesson, students learn how to analyze DNA sequence data from chromatograms using the bioinformatics tools FinchTV and BLAST. Using data generated by students in class or data supplied by the Bio-ITEST project, students will learn what DNA chromatogram files look like, learn about the significance of the four differently-colored peaks, learn about data quality, and learn how the data from multiple samples are used in combination with quality values to identify and correct errors. Students will use their edited data in BLAST searches at the NCBI and the Barcode of Life Databases (BOLD) to identify and confirm the source of their original DNA. Students then use the bioinformatics resources at BOLD to place their data in a phylogenetic tree and see how phylogenetic trees can be used to support sample identification. Learning these techniques will provide students with the basic tools for inquiry-driven research.

Wet Lab -- DNA Barcoding:  From Samples to Sequences
PowerPoint for Wet Lab

In this lesson, students perform the wet lab experiments necessary for DNA barcoding. Beginning with a small tissue sample, students purify the DNA, perform polymerase chain reaction (PCR) using COI-specific primer pools, and analyze their PCR products by agarose gel electrophoresis. PCR reactions that resulted in products of the correct size are subjected to PCR purification and submitted for DNA sequencing. This DNA sequence data can be used in Lesson Nine, or as part of an independent project.

Option Pre-Lab Exercise: Introduction to Micropipetting: Working with Small Volumes

Appendix

Resource Materials

PowerPoints to accompany each "Using Bioinformatics:  Genetic Research" lesson are found under the "Lessons" tab, below each lesson title.

See our Student Career Center for career profiles, planning resources, and more.

Lesson Two:  DNA Barcoding and the Barcode of Life Database

Unknown DNA Sequences:

1 - 2 - 3 - 4 - 5 - 6 - 7 - 8 - 9 - 10
11 - 12 - 13 - 14 - 15 - 16 - 17 - 18 - 19 - 20
21 - 22 - 23 - 24 - 25 - 26 - 27 - 28 - 29 - 30

 



Lesson Three:  Using Bioinformatics to Study Evolutionary Relationships

AND

Lesson Four:  Using Bioinformatics to Analyze Protein Sequences

Group Sequences:

Group
    
1       DNA       Protein       Outgroup
    2       DNA       Protein       Outgroup
    3       DNA       Protein       Outgroup
    4       DNA       Protein       Outgroup
    5       DNA       Protein       Outgroup

 



Lesson Five:  Molecular Murder Mystery

Protein Structures:

Cytochrome c oxidase structure

Carol Olds

Carl North

When opening each file, you may need to click "Open With" and "Browse."  Then select "Cn3D" from the program list.

 


 
Lesson Six: Assessment: Writing Research Reports

Research Poster Template

 



Lesson Nine:  Analyzing DNA Sequences and DNA Barcoding

DNA Chromatograms:
Be sure to download BOTH the "F" and "R" sequences for each sample.

BOC_25a_F.ab1

BOC_25a_R.ab1

BOC_030_F.ab1

BOC_030_R.ab1

BOC_032_F.ab1

BOC_032_R.ab1

BOC_033_F.ab1

BOC_033_R.ab1

BOC_035a_F.ab1

BOC_035a_R.ab1

BOC_036_F.ab1

BOC_036_R.ab1

 
Open Chromatograms using Finch TV.

 

 

PowerPoints to accompany each "Using Bioinformatics:  Genetic Research" lesson are found under the "Lessons" tab, below each lesson title.

Animations and Videos

"The Mitochondria" by BioVisions at Harvard University.  Incredible animation that shows in detail the inner workings of the mitochondria.   

Click here for a complete list of biology-related animations (by topics) from MolecularMovies.org, "A Portal to Cell & Molecular Animation."

Biochemistry and Molecular Structure Resources

3D Molecules

Protein Data Bank (PDB)
Search for the protein structures and either print, view online, or download to view with an appropriate plug-in (some of which can be downloaded from the site).  Features a "molecule of the month."  Also, visit the extensive Educational Resources Section.

NCBI's Structure Page allows you to view structures with a simple view, Cn3D, available for download from the site.  It also maintains its own structure database, MMDB, which is a subset of the PDB.

Biotechnology and Molecular Biology Curriculum

Access Excellence

About Biotech--A wealth of biotechnology information and resources, including career information and a graphics gallery.

Access Excellence/Woodrow Wilson Biotechnology Institute--A collection of biotechnology laboratory and classrom activities from Woodrow Wilson fellows.

Human Genome Project Education Resources
Wide range of educational materials related to the human genome project including publications, teaching aids, images, and downloadable PowerPoint presentations describing the project and its implications.

Cold Spring Harbor DNA Learning Center
Features a variety of high-quality resources for teaching about DNA, including introductory material about human evolution, bioinformatics, and eugenics images.

Animations Library (requires Shockwave, downloadable from site)
The PCR animations are an especially valuable resource for teaching this technique.

DNA From the Beginning--An animated primer of DNA, genes, and heredity.

Your Genes, Your Health--Provides information about genetic disorders.

Genetic Science Learning Center
Offers many valuable resources for teaching and learning about biotechnology.

Iowa State Biotechnology Resources for Educators
Includes thirteen laboratory activities, curriculum units, and more.  Topics include DNA extraction, fingerprinting, bacteria transformation, bioluminescence, plant micro propagation, a PCR activity, and a soybean flavor demonstration.

National Centre for Biotechnology Education (United Kingdom)
NCBE Publications--Download curriculum to teach biotechnology in the classroom, including plant biotechnology and fermentation.

ThinkQuest Genetic Experiments
Use readily available materials to simulate genetic research and develop an understanding of DNA extraction, how enzymes work, probability and heredity pools, individual genetic variations, and chromatography.  These experiments can be performed at home or school and come with both text and graphic demonstrations.

Beyond Discovery:  The Path from Research to Human Benefit
Real life case studies illustrate how recent medical and technological advances arose from basic laboratory research.  Some of the areas covered are Hepatitis B, polymers, designer seeds, and human gene testing.

Fred Hutchinson Cancer Research Center SEP Program Science and Education Links
An extensive collection of science links is available at Dyanna's Picks.  The downloadable resource list is especially valuable for Washington State educators.

NCBI
T
he National Center for Biotechnology Information has links to a wealth of resources for learning about biotechnology, including information on human genome resources, model organisms, and outreach/education.  Begin at the "About NCBI" section for a good overview of resources.  PubMed is a valuable resource for locating scientific research articles.

Washington Biotechnology and Medical Technology Online
The home page of WBBA, the Washington Biotechnology and Biomedical  Association (WBBA), provides information about biosciences in Washington State, as well as Education Materials such as a lab on gel electrophoresis and DNA fingerprinting.

WhyBiotech.Com
An informational site from the Council for Biotechnology Information.

Cell Biology Resources

Biology4Kids:  The Cell Biology Pages:  These pages cover all major cell organelles in detail with gorgeous color graphics and helpful analogies for understanding cellular functions.  Not just for "kids," this site would provide a terrific review for high school students as well.

The Biology Project provides cell biology resources in addition to addressing other aspects of biology.  It also offers activities, lesson plans, and tutorials.

Cells Alive provides a wonderful microscopic images of cells.  Check out the cell model tutorial and the cell gallery!

NCBI Bookshelf:  Search topics directly in the online versions of the classic texts of cell biology, Molecular Biology of the Cell, and Molecular Cell Biology.  This is an amazing resource!

Stem Cells

Medline:  Latest news on stem cell research from the National Library of Medicine.

PBS Newshour Online:  Human Stem Cell Research:  After reviewing background and a research interview on this controversial topic, view a three-minute animation on how human stem cells are cultured.  Embryonic stem cell issues are debated by medical ethicists.

Science Magazine:  Original article on "Embryonic Stem Cell Lines Derved From Human Blastocysts" in the October 1998 issue.

Stem Cell Primer from the NIH provides an overview of stem cells and issues related to their growth.

TIME magazine 2001 article on stem cells provides an introduction to the topic at the layperson's level.

Virtual Cell, An Education Index Top Site.  Zoom into the cell, cut sections, and learn about different organelles in this highly interactive site.

Neurobiology Resources

Digital Anatomist Interactive Atlas (Neuroanatomy):  This is an advanced program provided by the University of Washington that can be taken for credit, used in a classroom, or enjoyed for individual learning purposes.  Graphics and photos illuminate many components of the nervous system.  Online movies are available for every subject.  The overview details how to customize the program, label photos and diagrams, navigate the site, and how to use quiz mode.

Neuroscience for Kids--This home page has been created for all students and teachers who would like to learn more about the nervous system.  Enjoy the activities and experiments on your way to learning more about the brain and spinal cord.  This includes a scavenger hunt to help familiarize students with the site and nervous system.

Drugs and the Brain

Alcohol and Drug Abuse Institute, University of Washington
A Multidisciplinary Center at the University of Washington, whose mission is to support and facilitate research and research dissemination in the field of alcohol and drug abuse.  There is information about research being conducted and local clinical trials; in addition, there is an extensive list of links related to drug and alcohol abuse, treatment, and recovery.

American Council for Drug Education
Drug Prevention Lesson Plans
Lesson plans for K-12 grade levels.  Each lesson plan describes the objective of the leson, background on the topic, resources and teacher tips, and then the activities to plan for this class time.  There are also downloadable PDF files containing activity worksheets.
Tips for Talking About Drugs in the Classroom
Includes appropriate messages and communication strategies for talking to students about drugs.

National Institute on Drug Abuse (NIDA)
NIDA provides easy-to-use PowerPoint "Slide Teaching Packets" on several topics related to drugs and the brain, including:  The Brain and the Actions of Cocaine, Opiates, and Marijuana, The Neurobiology of Drug Addiction, and the Neurobiology of Ecstasy (MDMA).  NIDA and NIH also offer a free curriculum supplement called "The Brain:  Understanding Neurobiology through the Study of Addiction."

Click through some of the slideshows:
 --The Neurobiology of Drug Addiction
 --Bringing the Power of Science to Bear on Drug Abuse and Addiction

General Online Resources

Access Excellence is a great site for health and science teachers originally developed by Genetech.

Action Bioscience provides readings and curriculum ideas for topics such as biotechnology, the human genome, and a variety of other topics in biology.

The Biology Project provides activities, lesson plans, and tutorials, especially strong on problem sets, and tutorials.

The DNA Files--Experts and public radio watchdogs explore cutting edge topics in biomedical research.

The Genetics Science Learning Center (GSLC)--The GSLC partnership between scientists and educators produces innovative and effective genetic science learning programs utilizing information from leading-edge research.

The Science Lab offers links to many science-related sites, including science education resources.

Office of Science Education at NIH is an outstanding resource for teachers and students with access to a wealth of free curriculum materials.  Be sure to look at the valuable Curriculum Supplements, as well as the "Snapshots of Science and Medicine" newsletter.

The NIH has also created a Women in Science Career page, with complimentary videos, posters, and career profiles.  Other areas of the NIH site, such as NIH:  For the Public, may also be of interest.

Online Texts

Kimball's Biology Pages
Modified from the author's text "Biology" published in 1944 by Wm. C. Brown.  Search alphabetically or by search engine.  There are a lot of diagrams. 

NCBI Bookshelf
The bookshelf is growing number of biology reference boks that can be searched directly.  Several important biology reference texts, such as" Molecular Biology of the Cell" by Alberts et. al, and "Immunology" by Janeway et. al, are available.

Upcoming Advanced Bioinformatics: Genetic Research Events

An Introduction to Bioinformatics Teacher Workshop
Friday, February 3, 2012 - 18:00
Seattle
United States

This workshop will be presented on February 3 starting at 4pm and February 4 starting at 9am, 2012.

Program Description
The Northwest Association for Biomedical Research (NWABR) is excited to share our new bioinformatics program, Bio-ITEST: New Frontiers in Bioinformatics and Computational Biology funded by the National Science Foundation. Our curriculum, which was developed in collaboration with scientists, ethicists, and teachers, is comprised of two different units or “Strands.” The Introductory Strand, highlighted in this workshop, utilizes bioinformatics resources to teach basic concepts in molecular biology.  The Advanced Strand, currently in field testing, incorporates additional informatics resources and includes an authentic inquiry-based investigation specifically for advanced students.

Using the breast cancer susceptibility gene BRCA1 as a model, students are introduced to a collection of bioinformatics tools and explore the ethical issues surrounding genetic testing.  As biomedical researchers discover an increasing number of genes associated with susceptibility to disease, the era of “personalized medicine” is increasingly becoming a reality.  Students will need to understand disease risks and genetic penetrance, how genetic information is acquired, stored, and used, who has access to their information, and how genetic testing can influence personal and health decisions for themselves and their families.  Empowering students to understand the science behind genetic testing also reinforces lessons in evolution, transcription and translation, and the relationship between protein structure and function.

As part of this workshop teachers will receive:
• Basic background in bioethics
• An introduction to the National Center for Biotechnology Information (NCBI)
• Exposure to software for performing multiple sequence alignments
• Instruction on viewing macromolecules using Cn3D

Prior bioinformatics experience is not required.

Stipend, Clock Hours
Teachers will receive a $150 stipend for their participation in the 1.5 day professional development workshop. Nine clock hours will be provided free of charge. Dinner will be provided on Friday, February 4. Breakfast and lunch will be provided at the Saturday session. Teachers will also receive access to various bioinformatics resources.

Contact Jeanne Chowning, NWABR Director of Education, with questions or to request additional information. 206-957-3337, jchowning@nwabr.org

This program is made possible by

National Science Foundation

Innovative Technology Experiences for Students and Teachers grant award from the National Science Foundation, DRL-0833779