Using Technology to Study Cellular and Molecular Biology
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Using Technology to Study Cellular and Molecular Biology

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Teacher's Guide

Lesson 3—Explore, Explain, Elaborate

Putting Technology to Work

At a Glance

Overview

This lesson consists of a single activity with three parts in the Web version and four parts in the print version. It will take two days to complete. The lesson provides an opportunity for students to investigate some technologies that have advanced our understanding of cellular and molecular biology. Probe size, resolution, and using the right tool for the job are emphasized. Students are presented with a fictitious scenario involving the discovery of a muscle-wasting disease. As members of a medical and scientific team, they must choose a technology to use—light microscopy, transmission electron microscopy, cryo-electron microscopy, or X-ray crystallography—to investigate the disease. They answer questions such as, What is the infectious agent, how does the infectious agent cause disease, and is there a drug to treat or prevent the disease?

Major Concepts

Technologies that differ in their resolving capabilities provide different information about the structure of an object. Solving a problem requires an appropriate technology or series of technologies. Technology provides valuable tools for solving scientific problems relevant to human health.

Objectives

After completing this lesson, students will

Teacher Background

See the following sections in Information about Using Technology to Study Cellular and Molecular Biology:
3 Scale and Resolution
4 Major Techniques in the Study of Cellular and Molecular Biology

In Advance

Web-Based Activities
Activity Web Version?
1 Yes
Photocopies
For classrooms using the Web version of this activity:
  • Master 3.1, Memo from the Director, Global Science and Health Organization, 1 copy per group
  • Master 3.2, Research Plan, 1 copy per student and 1 transparency
  • Master 3.3, Example of a Research Plan, 1 transparency
  • Master 3.4, Drug Discovery Evaluation Form, 1 copy per student
For classrooms using the print version of this activity:
  • Master 3.1, Memo from the Director, Global Science and Health Organization, 1 copy per group
  • Master 3.2, Research Plan, 1 copy per student or 1 transparency for class
  • Master 3.3, Example of a Research Plan, 1 transparency
  • Master 3.5, Available Technologies, 1 transparency
  • Master 3.6, Science Reference Manual, 1 copy per group
  • Master 3.7, Muscle Protein Structures Determined by X-Ray Crystallography, 1 copy per group or 1 transparency for class
Materials
Activity 1 none required

 

Preparation

For classrooms using the Web version of this activity:
Verify that computer lab is reserved for two consecutive class periods or that classroom computers are ready to use. To save time, have computers at the URL http://science.education.nih.gov/technology/student. This is a main menu page from which this activity can be accessed.

For classrooms using the print versionof this activity:
No preparations needed.

Procedure

Web activity iconFor classrooms using the Web version of this activity.

Teacher note: This activity allows students to enter a virtual laboratory in which they use microscopic techniques and X-ray crystallography to solve a problem. The activity requires students to view and interpret data. An essential part of it is having students develop a logical research plan based in part on what they learned earlier in this module about scale and resolution. They should formulate hypotheses that can be tested with the technologies available to them.

Part 1, Solving the Problem

  1. Divide the class into groups of two students each, and give each group a copy of Master 3.1, Memo from the Director, Global Science and Health Organization.
  2. Ask students to read the memo and note the questions they are instructed to answer.

This memo also appears when students access the activity on the Web. Students can retain the printed memo to remind themselves of the questions they are to answer.

  1. Explain that students will begin by formulating a research plan. They will develop hypotheses that can be tested in their virtual laboratory.

If necessary, remind students that hypotheses are statements that predict a result and are testable experimentally.

  1. Ask students to proceed to http://science.education.nih.gov/supplements/technology/student. They should click on the link to “Lesson 3—Putting Technology to Work.” This brings up the unit’s desktop, from which this activity can be accessed.

After clicking on the activity link on the desktop, the memo from the director appears. After students close the memo, each of the four available technologies is highlighted. Note: Students should not yet click on a technology.

  1. Explain that students have resources available to them, including various technologies and reference materials. Ask students to click on the link to “Reference Manual.”

Briefly review the contents of the Reference Manual with the students.

Tip from the field test: Field-testing has indicated that it is very useful for teachers to introduce students to the Science Reference Manual early in this activity (see Teacher note 1, after Step 20). This resource contains valuable information to help students formulate their hypotheses, including the sizes of biological structures and resolution limits of various technologies, as well as details about unfamiliar technologies, blood cells, muscle cells, and pathogens and how they cause disease. At a minimum, you should introduce students to the table of contents of the Science Reference Manual, point out which topics are links to more information, and use one link to show students the kind of information provided.

  1. Ask students how they will begin their studies. What should they do first? Encourage student participation and accept all responses.

Teacher note: Even though students are in pairs, work with the class as a whole through Step 15 to help them understand the process.

This question is purposely vague. Its intent is to engage the students and initiate creative thinking. Student responses may vary considerably. Some students may suggest beginning at the lowest level of resolution, the eye, and visually confirming the presence of ill individuals. They may suggest talking with healthy and ill individuals to gain clues about the nature of the disease. They may want more details about symptoms. Indicate to students that while gaining additional information by talking with affected and unaffected individuals might be helpful, there is no time to travel. They need to get down to business and begin investigating the issues raised in the director’s memo.

  1. Direct students to the first question in the director’s memo. Choosing from the available technologies and using tissue samples from affected and unaffected individuals, how can they confirm the presence of disease at the cellular level in the affected population?

Students have muscle and blood samples available for study. Students should reason that light microscopy can be used to look for the presence of abnormal muscle cells in affected individuals. Unaffected individuals should have normal muscle cells. Students should provide a reason for wanting to look at any other tissue samples.

  1. Ask students, “Why would you use light microscopy to confirm the presence of disease?”

Students should know that cells are too small to be seen by the naked eye, although they can be seen easily with a light microscope. If necessary, ask students to think about the information on Master 1.1, Searching for Scale, (the size of a cell) and what they discovered in Lesson 2, Activity 1: Probing for Answers (start with the largest probe, in this case visible light).

National Science Education Standards icon
Content Standard A:
Identify questions and concepts that guide scientific investigations.

Content Standard A:
Design and conduct a scientific investigation.

  1. After deciding on a starting point (light microscopy), students should begin constructing their detailed research plan. Give each student a copy of Master 3.2, Research Plan.

Master 3.2 presents an example of how a research plan can be organized. It is important for students to see how information flows as an investigation proceeds and how what is done at one step depends on results from previous steps.

  1. Use the transparency of Master 3.2 to demonstrate how the research plan is constructed. Use Master 3.3, Example of a Research Plan, as your guide.
  2. In the space next to the statement, “To answer the question,” write the question, Is there evidence of disease at the cellular level (in muscle cells)? Ask students to help you determine which technology to use to answer this question.

Students should choose to begin their studies with light microscopy to look for the presence of abnormal cells in the muscle tissue of affected individuals. Write this response in the space next to the statement, “I will use this technology.”

  1. Ask students to respond to the statement, “I chose this technology because.”

Students should have reasoned that cells are too small to be seen with the naked eye but can be seen easily using a light microscope. In other words, the resolution of a light microscope is sufficient to see individual cells. Record the response on the transparency.

  1. Ask students to state a hypothesis.

There is (or is not) evidence of disease in muscle cells.

  1. Ask students what two results they would expect.

Either abnormal muscle cells will be seen in affected individuals or they will not. Record this response on the transparency.

  1. Ask students what question they would answer next if they observe abnormal muscle cells in affected individuals.

They would proceed to Question 2 on Master 3.1, Memo from the Director, Is the disease caused by an infectious agent? Record this response on the transparency.

  1. Ask students what question they would answer next if they do not observe abnormal muscle cells in affected individuals.

There is no single response to this question. Students can use their imagination.

Encourage students to use the Science Reference Manual to learn about muscle and blood cells. Examples of normal muscle and blood cells are included in the reference material. Information about the size of cells, bacteria, and viruses is also provided, as well as the various technologies students will investigate in this activity.

  1. Ask students to complete all tasks except those dealing with discovery of a drug to treat the disease (Question 6 on Master 3.1, Memo from the Director, Global Science and Health Organization).
  2. Instruct students to begin their studies. They should make careful observations at each step and record all of their observations. They should follow their research plan.

Circulate among groups as students work. Ensure that students are proceeding according to a rational plan they have developed. You may want to quiz students about why they selected a specific technology, what they hoped to see, how they interpret what they did see, or why a technology is appropriate for solving a specific problem.

Teacher notes:

1. Selecting a technology activates a short animation. For example, after clicking on the light microscope, the animation changes from a view of the whole instrument to the view students would have looking through the eyepiece. Then, a small window opens over an interactive screen. This window contains information about the samples available for investigation, such as what the sample is (for instance, tissue or protein), and the source of the sample (that is, from a person with the disease or from an unaffected individual). Samples are coded, and students should record the coding information.

2. The light microscope and the transmission electron microscope are interactive. Students should begin by selecting a sample and adjusting the brightness by moving the brightness slider. Magnification of the sample can be changed. Students can move most cell and tissue images up and down and to the left and right. Students may take a snapshot of a field they are viewing by clicking on the “View Snapshots.” Clicking on an individual snapshot produces a larger image that can be compared with another on-screen image (that is, an image on the microscope or an image in the Reference Manual). The “View Snapshot” window may be moved to allow easier comparison of images. Up to 12 snapshots may be stored.

3. Using the cryo-EM, students should click on “Affected” and “Unaffected.” They should record their observations of what appears in the electron microscope (left monitor) and in the three-dimensional reconstruction (right monitor).

4. After clicking on “X-ray Crystallography,” students see a detailed animation of the process. We indicate that the data were obtained from three different orientations of the protein crystal, which is far fewer than the thousands of different orientations actually used in a research laboratory. Students begin by making observations of the X-ray crystallography patterns that appear on screen. All that students—or scientists, for that matter—can judge at this point is that the patterns for the affected and unaffected proteins are different from one another for each orientation. Making sense of these data requires processing by high-speed computers using specialized software. Finally, students compare three-dimensional models of the affected and unaffected proteins. They should use the slider to rotate the proteins and record their observations of the differences and similarities of the proteins’ structures.

National Science Education Standards icon
Content Standard A:
Formulate and revise scientific explanations and models using logic and evidence.

Content Standard A:
Recognize and analyze alternative explanations and models.

Content Standard A:
Communicate and defend a scientific argument.

  1. When students have completed their work and answered Questions 1 through 5 on Master 3.1, Memo from the Director, Global Science and Health Organization, reconvene the class.
  2. One at a time, have groups share their findings with the rest of the class.

Presentations need not be long. However, students should demonstrate an understanding of scale, resolution, and selecting the right tool for the job. Members of each group should share the responsibilities of presenting the group’s information. Students should be encouraged to question the hypotheses, research plans, and interpretations of others. Remind students that science is a collaborative process in which scientists must be able to support their ideas.

Teacher notes:

1. The Science Reference Manual contains information that is very helpful to students, and they should consult it early in their investigations. For instance, students can view light micrographs of normal muscle. They will also find information on two common pathogens, bacteria and viruses, thus limiting the pathogens they search for. Additionally, key information about technologies is presented.

2. Students should reason that light microscopy can be used to look for the presence of abnormal muscle cells in affected individuals. Students generally know that cells are too small to be seen by the naked eye, although they can be seen easily with a light microscope. If necessary, ask students to think about the information on Master 1.1, Searching for Scale, (the size of cell) and what they discovered in Lesson 2, Activity 1: Probing for Answers (start with the largest probe, in this case visible light). In this activity, unaffected individuals have normal muscle cells. Individuals susceptible to disease have abnormal muscle cells.

3. The Science Reference Manual lists two common pathogens: bacteria and viruses. Students should focus on the 10- to 100-fold difference in size between bacteria and viruses. Light microscopy can be used to resolve bacteria, but not viruses. Students should understand that they are following a plan analogous to the one developed in Lesson 2. They are starting with the largest probe available (visible light) to find out about the largest possible structures that can be resolved.

4. No bacteria are visible in either muscle or blood samples. Therefore, students should use transmission electron microscopy to see whether viruses are present in any of the tissue samples. Viruses are readily visible with this technique, which uses a probe (electrons) that is smaller than the probe they used initially (visible light).

5. Transmission electron microscopy demonstrates the presence of viruses in blood and muscle tissue samples from one affected and one unaffected individual. A second set of unaffected blood and muscle samples does not contain viruses. This observation is a key finding for this activity, although it may be confusing to some students. How do students interpret the presence of virus and the absence of disease? How might this relate to how the virus produces disease in susceptible individuals? They can consult their Science Reference Manual for helpful information.

A possible reasoned scenario is 1) virus is present in muscle tissue of both affected and unaffected individuals because the virus binds to a protein receptor in that tissue, 2) the virus nucleic acid codes for a protein produced by the muscle cells, 3) the virus protein binds to a key muscle protein in cells of affected individuals, which causes the disease, 4) the virus protein does not bind to the muscle protein in cells of unaffected individuals, 5) the affected muscle protein has a different structure from the unaffected protein, and 6) this difference in structure allows the affected muscle protein to interact with the virus protein.

6. On the basis of the scenario presented above, a hypothesis might be as follows: the structure of the affected muscle protein is different from that of the unaffected muscle protein. An extension of this hypothesis is that the virus protein binds to the affected muscle protein and not the unaffected muscle protein because of differences in structure between the two muscle proteins.

7. On the basis of the scenario presented above, students can use cryo-EM to generate a three-dimensional reconstruction of the virus attached to the muscle to see whether the virus attaches to affected muscle fibers and not unaffected muscle fibers, and they can use X-ray crystallography to compare the structures of affected and unaffected muscle proteins.

8. To students—and to trained scientists, as well—the X-ray crystallography patterns are a collection of spots that do not themselves present a clear and obvious picture of a molecule’s structure. Students can note that the patterns differ from one another in spot location and intensity. They should understand that each pattern is unique because the structure being investigated is unique; that is, different patterns are produced both by different orientations of the same molecule and by different molecules. Students should also see the value of computer technology in providing three-dimensional molecular structure from a series of X-ray crystallography patterns. Please note that many more than three X-ray crystallography patterns are required to produce a three-dimensional structure. The process has been simplified for this activity.

9. Students should evaluate how the structure of the affected muscle protein compares with the unaffected muscle protein. The only visible difference between the two proteins is seen in the view along the z-axis (that is, from the top looking down). The affected muscle protein has an opening that is not present in the unaffected muscle protein.

Part 2, Applying Technology…Again

National Science Education Standards icon
Content Standard A:
Scientists conduct investigations for a wide variety of reasons, such as to discover new aspects of the natural world, to explain observed phenomenon, or to test conclusions of prior investigations or predictions of current theories.
  1. On behalf of the Global Science and Health Organization, thank students for their efforts. They have provided answers to some important questions. However, one very important question remains: Is there a drug to treat or prevent the disease?
  2. Ask students how the structural data on the affected and unaffected muscle proteins, obtained by X-ray crystallography, suggest a way that the virus could cause the disease.

Accept all responses. It is possible that the affected muscle protein can interact with the virus protein because its structure is different from that of the unaffected muscle protein. Students might wonder how this interaction could occur. They might speculate that the virus protein interacts with parts of the affected muscle protein around the opening that exists. It also may be that the virus protein interacts with some other region of the affected muscle protein. Alternatively, students may hypothesize that the virus causes the hole in the affected muscle protein. In other words, this action of the virus produces a muscle protein of changed structure and, therefore, changed function.

  1. How might a drug be used to treat the disease?

This is another opportunity for students to relate structure to function. They might reason that the affected muscle protein interacts with the virus protein and not the unaffected muscle protein because the two muscle proteins have different structures. This difference appears to be characterized primarily by an opening in the affected muscle protein. Therefore, perhaps a drug can be developed to change the affected muscle protein’s structure to one more like the unaffected muscle protein. A simple possibility is to develop a drug to close the opening. Students may suggest other possibilities as well. Do not limit their thinking or try to guide the discussion one way or another.

  1. Direct student groups to their computers. Tell them that the director of the Global Science and Health Organization has requested that they evaluate four new drugs that are believed to have potential to treat the disease.
  2. Give each student a copy of Master 3.4, Drug Discovery Evaluation Form. They should use this form to record their observations and interpretations.
  3. Ask students to click on the link “Drug Discovery Laboratory” on the unit’s desktop.

A memo appears that gives students the instructions for this activity. Students compare the unaffected muscle protein with a complex formed by combining a drug molecule with the affected muscle protein. Four different drug molecules are available. When students close the memo, a short animation comes on that leads to a screen on which appear the unaffected protein, the affected protein, and the four drug molecules. Students can make observations about their structures. Clicking on a drug molecule attaches that drug to the affected protein. Students should use the slider to rotate the two proteins and compare their structures.

The instructions to students are purposely general. Students should conclude that the drugs have been designed such that they either do or don’t convert the structure of the affected muscle protein to one more like the unaffected protein. Students will observe that none of the drugs interacts with the affected muscle protein to form a structure that is exactly the same as the unaffected muscle protein. This, too, is purposeful and is intended to stimulate student thinking.

Depending on the class time you have available, you can assign groups all four molecules to evaluate or a limited number of molecules (one or two) to evaluate.

Part 3, Wrapping It Up

  1. Reconvene the class. Ask groups to share their drug evaluations. What were the drugs apparently designed to do? Do any drugs show promise for treating the disease?

This discussion allows students to share thoughts about what they have done. They should focus on results and interpretations. Students should understand that the path to solving a scientific problem is long and complex and that technology plays a key role in the process. They also come to realize that there are not always neat solutions to problems.

National Science Education Standards icon
Content Standard A:
Formulate and revise scientific explanations and models using logic and evidence.
  1. Instruct students to prepare a report that summarizes their work.

They are to present their group’s work, from development of a research plan to drug discovery. It is acceptable for students to add their own touches to the group effort, based on class discussions and further reflection. They should focus on

  • justifying their choice of technology to solve specific problems,
  • demonstrating an understanding of specimen size and resolution, and
  • indicating a logical flow for using technologies of increasing resolution to solve problems.

For classrooms using the print versionof this activityprint activity icon

Teacher note: The print version of this activity is a “thought” activity. It does not make use of the graphics found in the Web activity, since these graphics do not always reproduce well. This version of the activity is more open-ended than the Web version. It allows students more latitude in formulating a research plan, since they are not restricted by available resources. Most important in this activity is the students’ reasoning. Why do they propose to use a given technology? What results do they expect? How will this lead them to the next step in their plan? Students work in groups to increase interaction and collaboration.

Part 1, What Is It?

  1. Divide the class into groups of three or four students each, and give each group a copy of Master 3.1, Memo from the Director, Global Science and Health Organization.
  2. Ask students to read the memo.
  3. Show students the transparency of Master 3.5, Available Technologies.

Tell students that to help them answer the questions raised by the director of the Global Science and Health Organization, the following technologies are available: observation by naked eye, light microscopy, transmission and cryo-electron microscopy, and X-ray crystallography. Remind them (as stated in the memo) that tissue samples from affected and unaffected individuals will be available.

National Science Education Standards icon
Content Standard A:
Design and conduct a scientific investigation.
  1. Give each group a copy of Master 3.6, Science Reference Manual. Explain to students that as scientists, they need reference materials to help them develop a logical and realistic research plan.

Tip from the field test: Field-testing indicated that it is very useful for teachers to introduce students to the Science Reference Manual early in this activity (see Teacher note 1, after Step 20 in the Web version procedure, above). This resource contains valuable information to help students formulate their hypotheses, such as sizes of biological structures and resolution limits of various technologies. It also contains information about unfamiliar technologies, such as X-ray crystallography, as well as about blood cells, muscle cells, and pathogens and how they cause disease. At a minimum, you should introduce students to the Table of Contents of the Science Reference Manual and point out the information provided there.

  1. Ask students how they will begin their studies. What should they do first? Encourage student participation and accept all responses.

Teacher note: Even though students are in smaller groups of three or four, work with the class as a whole through Step 14 to help them understand the process they will follow.

This question to students is purposely vague. Its intent is to engage the students and their imagination. Responses may vary considerably. Some students may suggest beginning at the lowest level of resolution, the eye, and visually confirming the presence of ill individuals. They may suggest talking with healthy and ill individuals to gain clues about the nature of the disease. They may want more details about symptoms. Indicate to students that while gaining additional information by talking with affected and unaffected individuals might be helpful, there is no time to travel. They need to get down to business and begin investigating the issues raised in the director’s memo.

  1. Direct students to the first question in the director’s memo. Choosing from the available technologies, and using tissue samples from affected and unaffected individuals, how can they confirm the presence of disease at the cellular level in the affected population?

If students ask what tissue samples are available, ask them to consider which tissue samples they would want and why. Students should reason that light microscopy can be used to look for the presence of abnormal muscle cells in affected individuals. Unaffected individuals should have normal muscle cells. Students should provide a reason for wanting to look at any other tissue samples.

  1. Ask students, “Why would you use light microscopy to confirm the presence of disease?”

Students should know that cells are too small to be seen by the naked eye, although they can be seen easily with a light microscope. If necessary, ask students to think about the information on Master 1.1, Searching for Scale (the size of a cell), and what they discovered in Lesson 2, Activity 1: Probing for Answers (start with the largest probe, in this case visible light).

  1. After deciding on a starting point (light microscopy), students should begin to create their detailed research plan. Master 3.2, Research Plan, presents an example of how a research plan can be organized.

Either give each student a copy of Master 3.2 or make a transparency of Master 3.2 to show the class. It is important for students to see how information flows as an investigation proceeds and how what is done at one step depends on results from previous steps. The research plan is constructed as a modified decision tree: if I see (result 1), I will do (next task); or, if I see (result 2), I will do (next task).

  1. Use the transparency of Master 3.2, Research Plan, to demonstrate how the research plan is constructed. Use Master 3.3, Example Research Plan, as your guide.
  2. Begin by writing the question, Is there evidence of disease at the cellular level (in muscle cells)?, in the space next to the statement, “To answer the question.” Ask students to help you deter-mine which technology to use to answer this question.

Students should begin their studies with light microscopy to look for the presence of abnormal cells in the muscle tissue of affected individuals. Write this response in the space next to the statement, “I will use this technology.”

  1. Ask students to respond to the statement, “I chose this technology because.”

Students should reason that cells are too small to be seen with the naked eye but can be seen easily using a light microscope. In other words, the resolution of a light microscope is sufficient to see individual cells. Record the response on the transparency.

  1. Ask students to state a hypothesis.

There is (or is not) evidence of disease in muscle cells.

  1. Ask students what two results they would expect.

Either abnormal muscle cells will be seen in affected individuals or they will not. Record this response on the transparency.

  1. Ask students what question they would answer next if they observe abnormal muscle cells in affected individuals.

Students would proceed to Question 2 on Master 3.1, Memo from the Director, Is the disease caused by an infectious agent? Record this response on the transparency.

  1. Ask students what question they would answer next if they do not observe abnormal muscle cells in affected individuals.

There is no single response to this question. Students can use their imagination.

  1. Inform students that they are ready to begin their studies. They should create their research plans in a manner similar to that demonstrated.
  2. Inform the class that results indicate the presence of abnormal muscle cells in tissue samples from affected individuals but not in unaffected individuals. First, they will address the question of whether or not the disease is caused by an infectious agent.

Students now begin working in smaller groups.

  1. The Science Reference Manual lists two common pathogens: bacteria and viruses. How could they identify one or the other as a potential cause of the disease (that is, as being present in affected individuals and not present in unaffected individuals) using the technologies available to them?

They should name the technology they would use, justify their choice based on the size of the objects they are looking for and the resolving power of the technology, and indicate possible results and what their next step would be. Allow groups no more than five minutes to formulate their plan.

  1. Ask a group to present its research plan very briefly.

Students should focus on the 10- to 100-fold difference in size between bacteria and viruses. Light microscopy can be used to resolve bacteria but not viruses. Students should understand that they are following a plan analogous to that developed in Lesson 2. They start with the largest probe available (visible light) to find out about the largest possible structures that can be resolved.

  1. Ask whether any groups have a different research plan.

Ask groups with a different research plan to make a brief presentation. Use class discussion to resolve differences or reinforce similarities.

National Science Education Standards icon
Content Standard A:
Formulate and revise scientific explanations and models.
  1. Inform the class that light microscopy did not demonstrate the presence of any structures resembling bacteria in tissue samples from affected or unaffected individuals. On the basis of this result, students should now formulate the next step in their research plan.

As before, students should name the technology they would use, justify their choice on the basis of the size of the objects they are looking for and the resolving power of the technology, and indicate possible results and what their next step would be. Allow groups two to three minutes to confirm their plan.

  1. Ask a group to present its research plan very briefly.

Students should use transmission electron microscopy to see whether viruses are present in any of the tissue samples. Viruses are readily visible with this technique, which uses a probe (electrons) that is smaller than the probe they used initially (visible light). Ask students to justify any other approach they suggest.

  1. Ask whether any groups have a different research plan.

Ask groups with a different research plan to make a brief presentation. Use class discussion to resolve differences or reinforce similarities.

Part 2, How Does It Work?

  1. Inform the class of the following results:
  1. Ask students to consider these results as they develop their plan to answer Questions 4 and 5 on the director’s memo (Master 3.1). For instance,

This may be a tough issue for students to deal with. It is not important for them to come up with our scenario. It is important for them to reason properly and use the available technologies to solve whatever problem they perceive exists. They should consult their Science Reference Manuals for helpful information.

A possible reasoned scenario is 1) virus is present in muscle tissue of both affected and unaffected individuals because the virus binds to a receptor in that tissue, 2) the virus nucleic acid codes for a protein produced by the muscle cells, 3) the virus protein binds to a key muscle protein in cells of affected individuals, which causes the disease, 4) the virus protein does not bind to the muscle protein in cells of unaffected individuals, 5) the affected muscle protein has a different structure from the unaffected protein, and 6) this difference in structure allows the affected muscle protein to interact with the virus protein.

  1. Ask groups to form a hypothesis based on their assessment of the data presented in Step 1 of Part 2.

On the basis of the sample scenario presented in Part 2, Step 2, one hypothesis might be as follows: the structure of the affected muscle protein is different from that of the unaffected muscle protein. A related hypothesis might be that the virus protein binds to the affected muscle protein and not the unaffected muscle protein because of differences in structure between the two muscle proteins. Another hypothesis is that the virus can attach to affected muscle fibers and not to unaffected muscle fibers. There are many possible hypotheses. It is important that each student hypothesis be a testable statement that predicts a result.

  1. Ask groups to formulate a plan to test their hypothesis. They should use only the techniques available to them.

On the basis of the sample scenario presented in Part 2, Step 2, students might propose to do the following:

Students might come up with other possibilities depending on the hypothesis they formulate.

National Science Education Standards icon
Content Standard A:
Communicate and defend a scientific argument.
  1. Ask a group to present its hypothesis and research plan.

Members of each group should share the responsibilities of presenting the group’s information. Students should be encouraged to question the hypotheses and research plans developed by others. Remind students that science is a collaborative process in which scientists must be able to support their ideas.

National Science Education Standards icon
Content Standard A:
Recognize and analyze alternative explanations and models.
  1. Ask whether any groups have a different hypothesis or research plan.

Ask groups with a different research plan to make a brief presentation. Use class discussion to resolve differences or reinforce similarities. On the basis of feedback from their fellow scientists, groups should be allowed to revise their hypotheses and research plans.

Part 3, What Can We Do about It?

  1. Thank students, on behalf of the Global Science and Health Organization, for their efforts so far. They must now think about developing a drug to treat this newly discovered disease.
  2. If the hypothesis students developed in Part 2 of this activity (about how the virus might produce disease) is supported by experimental data, how could students use a drug to treat the disease?

Even though students are still in groups, use this as an opportunity for class discussion. Accept all responses. This question is intentionally vague to stimulate student thinking. If students do not understand the concept of drug targeting (that is, designing a drug to interact specifically with another molecule, such as a host protein or a molecule produced by a pathogen), direct them to review the final item in Master 3.6, Science Reference Manual. The drug-specific molecule can be one associated with the pathogen, such as a bacterial or viral surface protein, or a protein produced by the pathogen. Alternatively, the drug-specific molecule can be one associated with the host, such as a receptor for the pathogen, or a molecule with which a pathogen-produced substance interacts.

  1. Tell students that new data have been obtained. Provide each group with a copy of Master 3.7, Muscle Protein Structures Determined by X-Ray Crystallography. Alternatively, use a transparency of this master for the class.
  2. Inform the class that the director of the Global Science and Health Organization wants them to evaluate these structures with their fellow scientists (the other group members) and answer a series of questions, which you will write on the board.
  1. Allow groups 10 to 15 minutes to work on their responses. After this time, reconvene the class and ask each group to present their answers.

Part 4, This, Too, Is What Science Is All About

National Science Education Standards icon
Content Standard A:
Scientists conduct investigations for a wide variety of reasons, such as to discover new aspects of the natural world, to explain observed phenomena, or to test conclusions of prior investigations or predictions of current theories.
  1. Remind students that reporting their results is also an important part of doing science. That is what they must do now.
  2. Instruct students to prepare a report that summarizes the work done within their group.

Students are to present all of their group’s work, from development of a research plan to drug discovery. It is acceptable, based on class discussions and further reflection, to add their own touches to the group effort. Student reports should

Web activity icon Lesson 3 Organizer: Web Version
Activity 1: Putting Technology to Work
What the Teacher Does Procedure Reference

Part 1, Solving the Problem

 
Divide the class into groups of two.
  • Give each group a copy of Master 3.1, Memo from the Director, Global Science and Health Organization.
  • Ask students to read the memo.
  • Explain that they will begin by formulating a research plan.
  • Have students access the activity and click on the link to the Reference Manual.
  • Briefly review the contents of the Reference Manual.

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Steps 1–5

Help students develop a research plan.
  • Ask students how they would begin their studies.
  • Guide students to the use of light microscopy to confirm the presence of disease at the cellular level in affected people.
  • Give each student a copy of Master 3.2, Research Plan.
  • Use a transparency of Master 3.2 to demonstrate how a research plan is developed.
  • With student input, fill in the required information on the transparency. Use Master 3.3, Example of a Research Plan, as a guide.
  • In the space next to the statement, "To answer the question," write the question, Is there evidence of disease at the cellular level (in muscle cells)? Ask students to help you determine which technology to use to answer this question.
  • Ask students to respond to the statement, "I chose this technology because."
  • Ask students to state a hypothesis.
  • Ask students what two results they would expect.
  • Ask students what question they would answer next if they do not observe abnormal muscle cells in affected individuals.

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Steps 6–16

Instruct students to begin their studies. They should construct their research plans in a manner similar to that demonstrated. They should complete all tasks except the one dealing with drug discovery (Question 6 on Master 3.1, Memo from the Director, Global Science and Health Organization). Have groups share their findings.

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Steps 17–20

Part 2, Applying Technology…Again  
Remind students of the final question to be answered: Is there a drug to treat or prevent the disease?

Step 1

Ask students,
  • how the structural data on the affected and unaffected muscle proteins, obtained by X-ray crystallography, suggest a way that the virus could cause the disease and
  • how a drug might be used to treat the disease.

Steps 2–3

Direct students to computers.
  • Tell students that they are to evaluate four new drugs that are believed to have potential to treat the disease.
  • Give each student a copy of Master 3.4, Drug Discovery Evaluation Form, on which they should record their observations and interpretations.
  • Ask students to click on the link for the Drug Discovery Laboratory on the unit’s desktop and complete the activity.

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Steps 4–6

Part 3, Wrapping It Up

 
Reconvene the class. Ask groups to share their drug evaluations.
  • What were the drugs apparently designed to do?
  • Do any drugs show promise for treating the disease?

Step 1

Instruct students to prepare a report that summarizes their work.

Step 2

master icon = Involves copying a master. transparency icon = Involves using a transparency. Web activity icon = Involves using the Internet.

 

print activity icon Lesson 3 Organizer: Print Version
Activity 1: Putting Technology to Work
What the Teacher Does Procedure Reference
Part 1, What Is It?  

Divide the class into groups of three or four.

  • Give each group a copy of Master 3.1, Memo from the Director, Global Science and Health Organization.
  • Ask students to read the memo.
  • Show students the transparency of Master 3.5, Available Technologies.
  • Give each group a copy of Master 3.6, Science Reference Manual.

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Steps 1–4

Ask students how they will begin their studies. Direct attention to the first question on the director’s memo. Ask,

  • “Choosing from the available technologies and using tissue samples from affected and unaffected individuals, how can you confirm the presence of disease at the cellular level in the affected population?”
  • “Why would you use light microscopy to confirm the presence of disease?”

Steps 5–7

After deciding on a starting point, students should begin constructing their research plan.

  • Use the transparency of Master 3.2, Research Plan, to demonstrate how the research plan is constructed.
  • With student input, fill in the required information on the transparency. Use Master 3.3, Example of a Research Plan, as a guide.
  • In the space next to the statement, "To answer the question," write the question, Is there evidence of disease at the cellular level (in muscle cells)? Ask students to help you determine which technology to use to answer this question.
  • Ask students to respond to the statement, "I chose this technology because."
  • Ask students to state a hypothesis.
  • Ask students what two results they would expect.
  • Ask students what question they would next answer if they do not observe abnormal muscle cells in affected individuals.

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Steps 8–16

Inform the class that results indicate the presence of abnormal muscle cells in tissue samples from affected individuals but not in unaffected individuals.

  • The class will first address the question of whether or not the disease is caused by an infectious agent.
  • Their science reference manual lists two common pathogens: bacteria and viruses.
  • Ask students how they could identify one or the other as a potential cause of the disease using the technologies available to them.
  • Ask a group to present its research plan.
  • Ask if any groups have a different research plan.

Steps 17–20

Inform the class that light microscopy did not demonstrate the presence of any structures resembling bacteria in tissue samples from affected or unaffected individuals.

  • On the basis of this result, students should now formulate the next step in their research plan.
  • Ask a group to present its research plan.
  • Ask whether any groups have a different research plan.

Steps 21–23

Part 2, How Does It Work?  

Inform the class of the following results:

  • transmission electron microscopy demonstrated the presence of viruses in blood and muscle tissue samples from both affected and unaffected individuals;
  • no other tissue samples contained viruses;
  • there were more viruses in muscle of affected people than in unaffected people; and
  • the viruses appeared to be associated with actin filaments in the muscle.

Step 1

Ask students to consider these results as they develop their plan to answer Questions 4 and 5 on the director’s memo. For instance,

  • how do students interpret the presence of virus and the absence of disease, and
  • how might this relate to how the virus produces disease in susceptible individuals?

Step 2

Ask groups

  • to form a hypothesis based on their assessment of the data presented in Step 1, Part 2, and
  • to formulate a plan to test their hypothesis.

Steps 3–4

Ask a group to present its hypothesis and research plan.

Step 5

Ask if any groups have a different hypothesis or research plan.

Step 6

Part 3, What Can We Do About It?  
Inform the class that they must now think about developing a drug to treat the disease.

Step 1

On the basis of the hypotheses they developed in Part 2, how might students use a drug to treat the disease?

Step 2

Tell students that new data have been obtained. Give each group a copy of Master 3.7, Muscle Protein Structures Determined by X-Ray Crystallography, or use a transparency for the class.
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Step 3

Inform the class that they are to evaluate these structures and answer a series of questions, which you write on the board.

  • How does the structure of the affected muscle protein compare with the unaffected muscle protein?
  • Do these results support a way that the virus could cause the disease?
  • What approach might be taken to develop a drug to treat the disease?
  • Using the technologies available, how could potential drugs be tested for effectiveness before using them to treat humans?

Step 4

Allow groups 10 to 15 minutes to work on their responses. Reconvene the class and ask each group to present their answers.

Step 5

Part 4, This, Too, Is What Science Is All About  
Remind students that reporting their results is also a part of doing science.

Step 1

Instruct students to prepare a report that summarizes the work done within their group.

Step 2

master icon = Involves copying a master. transparency icon = Involves using a transparency.  

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