On the trail of viruses: understanding virus research Teach article

DNA-based methods such as PCR, gel electrophoresis and bioinformatics, provide a practical insight into virus research for students – applicable to COVID-19, bird flu and others.

Viral pathogens like SARS-CoV-2, bird flu and Ebola pose recurring global challenges requiring rapid scientific response.^[1] In this unit, students apply molecular biology methods to compare virus variants at the DNA level using a bioinformatics software. They explore essential questions: Why are primers needed? What makes mutations dangerous?^[2] How does bioinformatics aid vaccine development?^[3,4] Activities connect to real research at the European XFEL (X-Ray Free-Electron Laser Facility), where scientists use ultra-short X-ray pulses to visualise SARS-CoV-2 proteins.^[5] This demonstrates the modern science of being networked, data-driven and socially relevant. As well as acquiring specialised knowledge, students develop scientific thinking skills such as precise observation, logical reasoning, and critical evaluation using methods applicable across viral diseases.^[6]

Activity 1: Short movie about virus research

A short, visually impressive video gives the students an initial insight into modern virus research. The focus is on how large-scale scientific research facilities, such as the European XFEL, help to visualise new virus structures, which form the basis for vaccine development, drug research and pandemic preparation.

Materials

• Laptop, tablet or mobile phone with browser
• Video: Virus research at European XFEL
• Worksheet A
• Solution worksheet A
• Discussion answers 

Procedure

1. Start with a short thematic introduction (2–3 min), asking the following questions:
   a) How do you investigate something that you can barely see with a microscope?
   b) What role does physical technology play in biology?
2. Watch the video together (approx. 10 min) (Note: The video can also be watched individually in advance or at home).
3. Work on Worksheet A in individual or partner work.

Results/discussion

The solutions for each task can be found in the supplemental materials Solution worksheet A.

As a teacher, you will moderate a joint evaluation in a plenary session:

• What surprises you about the connection between physics and biology?
• Why does modern biology need international research institutions?
• Could such methods also help with other viruses?

A detailed explanation for each of these questions can be found in the Discussion answers.

Activity 2: DNA sequence analysis – Understanding mutations in SARS-CoV-2

This lesson introduces students to DNA sequence analysis using real SARS-CoV-2 variants. Using the free MEGA software, students will learn to identify point mutations by comparing spike protein gene sequences from the wild type, Delta and Omicron variants. This hands-on activity demonstrates how mutations arise, how they’re detected and their potential effects on the protein structure and function. Students will gain practical experience of how to use bioinformatics tools, while developing an understanding of the evolutionary processes that drive viral adaptation.

Duration: 90–120 min

Material

Per student or pair:

• Computer with internet access
• MEGA 11 software (free download from https://www.megasoftware.net/)
• Provided DNA sequence files (sequence.fas format)
• Info sheet sequence analysis
• Worksheet B with guided questions, coding circle and amino acid structure chart 
• Solution worksheet B
• Discussion answers

Teacher preparation:

• Install MEGA 11 on all computers 1–2 days before lesson.
• Test the software and familiarise yourself with the interface.
• Prepare the sequence.fas file with the wild type, Delta and Omicron sequences.
• Print the worksheets and reference materials.
• Review the mutation nomenclature (e.g., G102Y format).

Procedure

Phase 1: Software Introduction (15 min)

1. Demonstrate how to open MEGA and how to load the sequence file (File → Open A File/Session).
2. When prompted “Analyse or Align File?” select “Align”.
3. Show students the initial unaligned sequences.
4. Have students complete task 1: observing the start codon (ATG) and initial sequence structure.

Phase 2: Sequence alignment (20 min)

1. Guide students through the alignment procedure: Alignment menu → “Align by MUSCLE (Codons)”.
2. Accept the default parameters and select “Yes” when asked to remove gaps.
3. Choose the “w/o gaps” option in the alignment window.
4. Students complete task 2: comparing aligned vs unaligned sequences and identifying mutation examples.

Phase 3: Mutation investigation (35 min)

1. Demonstrate navigation using the “Site #” field at bottom left.
2. Explain codon positioning: divide the site number by 3 to determine the position within a codon.
3. Students examine four specific mutation sites (205–210, 642–643, 1501–1503, 2041–2043).
4. For each site, students identify:
   • which variant is mutated;
   • the type of point mutation;
   • the nucleotide changes;
   • the resulting amino acid changes (using codon table in Worksheet B).
5. Verify results using the “Translated Protein Sequences” function.

Phase 4: Analysis and discussion (25 min)

1. Students complete task 4, analysing:
   • deletion mutation Δ69–70 and PCR detection implications;
   • side chain properties in N501Y mutation;
   • effects of P681R (Delta) and P681H (Omicron) near cleavage sites.
2. Discuss with the whole class the functional consequences of mutations.
3. Explain the connection of mutations to selection pressure and viral evolution concepts.

Phase 5: Extension activities (homework)

• Students may research artificial virus modifications (gain-of-function research).
• Students may investigate the PCR testing methodology for COVID-19 detection.

Results/Discussion

Students should identify silent, missense and nonsense mutations and recognise that missense mutations predominate in viable viral variants. The Δ69–70 deletion demonstrates how mutations affect diagnostic testing. The analysis of amino acid side chains (polar, nonpolar, charged) reveals how mutations alter protein interactions and potentially affect viral infectivity. The solutions for each task can be found in the supplemental materials in the Solution worksheet B.

Discussion points could be:

• Why do certain mutations appear in multiple variants?
• How does selection pressure drive mutation accumulation?
• What role do amino acid properties play in protein function?
• Why might some mutations increase viral transmission?

A detailed explanation for each of these questions can be found in the Discussion answers.

Evaluate the worksheets of your students for accuracy in mutation identification, codon translation, and understanding of structure-function relationships in proteins.

Activity 3: Primer design – a work sheet orientated task

This exercise teaches students how to design DNA primers for PCR applications. Students will learn about DNA structure and base pairing rules as well as calculate primer specificity and melting temperatures using mathematical formulas.

Materials

• Info sheet primer design
• Worksheet C
• Solution worksheet C

• Discussion answers
• Calculator or computer
• Pencil and paper
• Optional: internet access to demonstrate the primer design with the software 

Procedure

Part 1: Understanding primer specificity

1. Review with your students the DNA structure: four bases (A, T, G, C) with complementary pairing (A-T, G-C),
2. Explain that primers are 15–30 nucleotides long and must bind specifically to the target DNA.
3. Calculate possible combinations for different primer lengths using the formula 4ⁿ (where n is the number of nucleotides).
4. Students complete task 1: Calculate combinations for 8-nucleotide and 17-nucleotide primers.
5. Divide 3 billion (human genome base pairs) by your calculated combinations to find potential binding sites.
6. Discuss why longer primers (17–28 nucleotides) are more specific.

Part 2: Calculating melting temperature

1. Introduce the melting temperature (T_m) formula T_m = 4 × (G+C) + 2 × (A+T) [°C].
2. Explain that annealing temperature (T_a) is 1–2°C below T_m.
3. Students complete task 2: Calculate T_m for three given primer sequences.
4. Count the G/C and A/T bases in each sequence.
5. Apply the formula and determine the optimal annealing temperatures.
6. Discuss how the GC content affects primer stability and why proper temperature selection prevents non-specific binding.

Results/Discussion

Students should find that 8-nucleotide primers have too many potential binding sites, while 17+ nucleotide primers are sufficiently specific. The solutions for each task can be found in the supplemental materials in the Solution worksheet C and the answers to the discussion points in the Discussion answer.

Acknowledgements

This article could not have been written without the funding of the Joachim Herz Foundation (https://www.joachim-herz-stiftung.de/en/), who funded the work of Anusha Veena and the materials used. I would like to especially thank Anusha Veena for her work and input in creating these activities together with Sarah Aretz and Arwen Cross from the European XFEL GmbH. 

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Supporting materials

Info sheet: Primer design

Info sheet: Sequence analysis

Worksheet A: Virus video

Solution Worksheet A

Worksheet B: Sequence analysis

Solution worksheet B

Worksheet C: Primer design

Solution worksheet C

Discussion answers

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