Advanced Bioinformatics: Genetic Research

 

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

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 Unit Overview (PDF).  This contains authors and contributors, lesson summaries, instructional requirements, and lesson correlations to National Science Standards and the Next Generation Science Standards.

In order for us to measure how our curriculum resources are being used, please take a moment to contact us and let us know the class or classes in which you're using our lessons.  We also welcome feedback about our advanced bioinformatics curriculum. We will not share your contact information with anyone.

Major collaborators include Digital World BiologyEdLab 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.

 

Lessons

This curriculum unit explores how bioinformatics is used to perform genetic research. Specifically, the bioinformatics tools BLAST, ORFinder, ClustalW2/JalView, and Cn3D are used to analyze genetic sequences and molecular structures. 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 optional authentic student research project, sequencing the COI genes from samples they collect themselves or samples obtained through partnerships with the National Oceanographic and Atmospheric Association (NOAA) and the Seattle Aquarium, both based in Seattle. Throughout the unit, students are exposed to a number of career options where bioinformatics tools are either 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.

    Complete Lesson Plans
  • Lesson One: The Process of Genetic Research Genetic_Research_Lesson1_NWABR.pdf

    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 and 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. In Lesson One, students learn how DNA sequencing core lab managers might use bioinformatics tools in their career.

  • Lesson Two: DNA Barcoding and the Barcode of Life Database (BOLD) Genetic_Research_Lesson2_NWABR.pdf

    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 each student generating a hypothesis about the relatedness of the species within each group. In Lesson Two, students learn how postdoctoral scientists in DNA and history might use bioinformatics tools in their career.

  • Lesson Three: Using Bioinformatics to Study Evolutionary Relationships Genetic_Research_Lesson3_NWABR.pdf

    In this lesson, students learn how to use bioinformatics tools to analyze DNA sequence data and draw 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. In Lesson Three, students learn how microbiologists might use bioinformatics tools in their career.

  • PowerPoint for Lesson Three Genetic_Research_Lesson3_Slides_NWABR.ppt
  • Lesson Four: Using Bioinformatics to Analyze Protein Sequences Genetic_Research_Lesson4_NWABR.pdf

    In this lesson, students perform a paper exercise designed to reinforce student understanding of the complementary nature of DNA and how that complementarity leads to six potential protein reading frames in any given DNA sequence. They 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. In Lesson Four, students learn how biological anthropologists might use bioinformatics tools in their career.

  • PowerPoint for Lesson Four Genetic_Research_Lesson4_Slides_NWABR.ppt
  • Lesson Five: Protein Structure and Function: A Molecular Murder Mystery Genetic_Research_Lesson5_NWABR.pdf

    Prior to this lesson, students learned how the cytochrome c oxidase subunit 1 (COI) gene is used to barcode animals. 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 determine the identity of a foreign substance that acts as a poison by binding to the active site. This lesson allows students to explore the use of the molecular visualization program Cn3D to learn more about cytochrome c oxidase, a ubiquitous and important protein. In Lesson Five, students learn how molecular diagnostics researchers might use bioinformatics tools in their career.

  • PowerPoint for Lesson Five Genetic_Research_Lesson5_Slides_NWABR.ppt
  • Lesson Six: Genetic Research Unit Assessment: Writing Research Reports Genetic_Research_Lesson6_NWABR.pdf

    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, andReferences 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, writing a scientific abstract, or writing a science-related magazine article. In Lesson Six, students learn how science and technical writers might use bioinformatics tools in their career.

  • Lesson Seven: Who Should Pay? Funding Research on Rare Genetic Diseases Genetic_Research_Lesson7_NWABR.pdf

    In this lesson, 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 defects in one of several proteins, including cytochrome c oxidase subunit 1, the protein encoded by the DNA barcoding gene, and examined in Lesson 5. Without the COI protein, cells are unable to 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 stakeholder’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. In Lesson Seven, students learn how pediatric neurologists might use bioinformatics tools in their career.

  • PowerPoint for Lesson Seven Genetic_Research_Lesson7_Slides_NWABR.ppt
  • Lesson Eight: Exploring Bioinformatics Careers Genetic_Research_Lesson8_NWABR.pdf

    In this lesson, 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 also learn about writing cover letters. Optional extensions include peer-editing of resumes and a mock interview for a job related to a career of interest.

  • PowerPoint for Lesson Eight Genetic_Research_Lesson8_Slides_NWABR.ppt
  • Lesson Nine: Analyzing DNA Sequences and DNA Barcoding Genetic_Research_Lesson9_NWABR.pdf

    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 learn what DNA chromatogram files look like, learn about the significance of the four differently-colored peaks, learn about data quality, and learn how data from multiple samples are used in combination with quality values to identify and correct errors. Students use their edited data in BLAST searches at the NCBI and the Barcode of Life Database (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.

  • Lesson Nine Adaptation: Working with a Single DNA Sequence Analyzing-A-DNA-Sequence-Chromatogram.pdf

    This Lesson Nine Student Handout is used for classes in which students are analyzing only one (not two) DNA chromatogram. 

  • PowerPoint for Lesson Nine Genetic_Research_Lesson9_Slides_NWABR.ppt
  • PowerPoint for Lesson Nine Adaptation: Working with a Single DNA Sequence Genetic_Research_Lesson9_Slides_Single_Sequence_NWABR.ppt
  • Wet Lab: DNA Barcoding: From Samples to Sequences Genetic_Research_Wet_Lab_NWABR.pdf

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

Resources

Resource Materials

PowerPoints to accompany each "Using Bioinformatics:  Genetic Research" lesson are found on the "Lessons" page, beside 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

DNA Barcoding Animation.  New animation to accomany the advanced bioinformatics curriculum!

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 3:  Using Bioinformatics to Study Evolutionary Relationships

AND

Lesson 4:  Using Bioinformatics to Analyze Protein Sequences

Group SequencesDNAProteinOutgroup (DNA)
Group 1: Class Mammalia (Mammals) DNAProtein  Outgroup
Group 2: Class Aves (Birds)DNAProteinOutgroup
Group 3: Class Osteichthyes (Bony Fishes) DNAProteinOutgroup
Group 4: Class Chondrichthyes (Cartilaginous Fishes)DNAProteinOutgroup
Group 5: Class Reptilia (Reptiles)DNAProteinOutgroup

Lesson 5:  Molecular Murder Mystery

Protein Structures:

Cytochrome oxidase structure

Carol Olds

Carl North *

* To open the "Carl North" file, right click on the link (PC) to save the file to your desktop prior to opening. [For Mac users, click the "Carl North" link, select "Save As," and then save the file to your Desktop]

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.

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