Lesson: Imaging DNA Structure

Contributed by: University of Houston, National Science Foundation GK-12 and Research Experience for Teachers (RET) Programs

A computer-generated image shows a lumpty glob of biomolecules.
Engineering advances have made possible computer-generated images, such as this rendition of a restriction enzyme (in gray) attached to a DNA double helix.
copyright
Copyright © Nature http://www.nature.com/scitable/spotlight/restriction-enzymes-18458113

Summary

Students are introduced to the latest imaging methods used to visualize molecular structures and the method of electrophoresis that is used to identify and compare genetic code (DNA). Students should already have basic knowledge of genetics, DNA (DNA structure, nucleotide bases), proteins and enzymes. The lesson begins with a discussion to motivate the need for imaging techniques and DNA analysis, which prepares students to participate in the associated two-part activity: 1) students each choose an imaging method to research (from a provided list of molecular imaging methods), 2) they research basic information about electrophoresis.
This engineering curriculum meets Next Generation Science Standards (NGSS).

Engineering Connection

Visualization of small structures such as the molecular structures of complex proteins and genetic material (DNA) is based on engineering discoveries and breakthroughs in physics at small scales. Imaging technologies such as x-ray and scanning electron microscopy—used by scientists and engineers to image microscopic structures—are also used by biomedical engineers and biologists to study biomolecules, cells and tissue samples. Microfluidics concepts and devices used to study colloidal particle flow are also employed by biologist to study and filter biomolecules. Gel electrophoresis is one example of the many engineering technologies that biologists use to compare fragments of DNA samples.

Pre-Req Knowledge

Basic knowledge about genetics: DNA, the four nucleotide bases and the base pairing rules, DNA double helix structure.

Learning Objectives

After this lesson, students should be able to:

  • Enumerate some of the imaging technologies used for atomic scale microscopy.
  • List the basic, underlying principles of the researched microscopy method.
  • Describe how the microscopy method helped scientists to discover the structure of biomolecules.
  • Explain the difference between molecular imaging and DNA gel electrophoresis.
  • Explain that certain nucleotide base sequences in the DNA encode for proteins/enzymes, whereas the molecular shape of protein/enzyme determines their functions.

More Curriculum Like This

Inside the DNA

Students conduct their own research to discover and understand the methods designed by engineers and used by scientists to analyze or validate the molecular structure of DNA, proteins and enzymes, as well as basic information about gel electrophoresis and DNA identification.

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Introduction to Genetic Engineering and Its Applications

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DNA: The Human Body Recipe

As a class, students work through an example showing how DNA provides the "recipe" for making human body proteins. They see how the pattern of nucleotide bases (adenine, thymine, guanine, cytosine) forms the double helix ladder shape of DNA, and serves as the code for the steps required to make gene...

Middle School Lesson
Restriction Enzymes and DNA Fingerprinting

Students focus on restriction enzymes and their applications to DNA analysis and DNA fingerprinting. They use this lesson and its associated activity in conjunction with biology lessons on DNA analysis and DNA replication.

Educational Standards

Each TeachEngineering lesson or activity is correlated to one or more K-12 science, technology, engineering or math (STEM) educational standards.

All 100,000+ K-12 STEM standards covered in TeachEngineering are collected, maintained and packaged by the Achievement Standards Network (ASN), a project of D2L (www.achievementstandards.org).

In the ASN, standards are hierarchically structured: first by source; e.g., by state; within source by type; e.g., science or mathematics; within type by subtype, then by grade, etc.

  • Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells. (Grades 9 - 12) Details... View more aligned curriculum... Do you agree with this alignment?
  • The sciences of biochemistry and molecular biology have made it possible to manipulate the genetic information found in living creatures. (Grades 9 - 12) Details... View more aligned curriculum... Do you agree with this alignment?
  • Technological progress promotes the advancement of science and mathematics. (Grades 9 - 12) Details... View more aligned curriculum... Do you agree with this alignment?
  • know that hypotheses are tentative and testable statements that must be capable of being supported or not supported by observational evidence. Hypotheses of durable explanatory power which have been tested over a wide variety of conditions are incorporated into theories; (Grades 9 - 11) Details... View more aligned curriculum... Do you agree with this alignment?
  • know scientific theories are based on natural and physical phenomena and are capable of being tested by multiple independent researchers. Unlike hypotheses, scientific theories are well-established and highly-reliable explanations, but they may be subject to change as new areas of science and new technologies are developed; (Grades 9 - 11) Details... View more aligned curriculum... Do you agree with this alignment?
  • distinguish between scientific hypotheses and scientific theories; (Grades 9 - 11) Details... View more aligned curriculum... Do you agree with this alignment?
  • plan and implement descriptive, comparative, and experimental investigations, including asking questions, formulating testable hypotheses, and selecting equipment and technology; (Grades 9 - 11) Details... View more aligned curriculum... Do you agree with this alignment?
  • analyze the levels of organization in biological systems and relate the levels to each other and to the whole system. (Grades 9 - 11) Details... View more aligned curriculum... Do you agree with this alignment?
Suggest an alignment not listed above

Introduction/Motivation

(Have ready to show students an assortment of molecular images of DNA, RNA, proteins and enzymes. See the Additional Multimedia Support section for a link to an online image database.)

Have you ever been curious about how your DNA might affect your chances of developing diseases and disorders? Do you ever wonder how scientists and doctors are able to study human DNA? Today we are going to learn about how engineering advances over decades have allowed scientists, doctors and other engineers to be able to visualize DNA and its structure.

The molecular structure of proteins and enzymes is very complex and plays a fundamental role in their functions. Slight changes in shape, known as protein folding, can result in anomalous function with adverse effects on the health of cells and of organisms. It has been recognized that many diseases and disorders are the result of protein/enzyme malfunctions; therefore, determining the structure of proteins and enzymes can help scientists and doctors develop more effective cures and treatments. Also, identifying which parts of the genetic code (DNA) are used as templates for the production of important proteins and enzymes is another major area of research interest. While the DNA structure is known, the important DNA segments that encode proteins are not entirely known and extensive research is performed to locate and identify them.

Genetics and the study of biomolecules, such as proteins and enzymes, rely in part on theoretical/computational models and on atomic scale microscopy. In particular, the discovery of the DNA structure—the double helix—and its replication and transcription processes has led to new discoveries in molecular biology and medicine. For years, scientists have tried to predict the arrangement of molecules (nucleotide bases, phosphate and sugar groups) that make up DNA using theoretical models based on the atomic and molecular interactions, but no validation or comparison between the structure predicted by models and the real structure existed. In 1953, the double helix structure of DNA based on x-ray analysis was published. A decade later, atomic force microscopy and other ultra-high resolution microscopy technologies were able to confirm this finding.

(Show students some molecular images of DNA, RNA, proteins and enzymes.) How have scientists been able to figure out the complex shapes of these tiny molecules? How do scientists know that the DNA or the hemoglobin look the way they do? Is it possible to look at the crystalline structure of molecules? The answer is yes, but not by using conventional microscopy. Instead, more complex technologies had to be invented, such as x-ray diffraction, transmission electron microscope (TEM), atomic force microscopy, fluorescence resonance energy transfer, magnetic resonance force microscopy, etc. What are these technologies? How do they work? What are the basic principles behind them? These questions all relate to modern molecular imaging. All these questions will be answered during this lesson and our discussion, and by your research (via the associated activity).

Lesson Background and Concepts for Teachers

Artistic rendering of hemoglobin showing the molecular structure using a ribbon representation.
Figure 1. The hemoglobin protein found in blood is responsible for oxygen transport. Mutations in the protein alter its molecular structure and can reduce its affinity for oxygen binding. Oxygen binds to hemes groups (in red).
copyright
Copyright © 2010 Pittsburgh Supercomputing Center http://www.psc.edu/science/Ho/Ho.html

The molecular structure of chemical compounds and biological macromolecules (DNA, proteins) has been determined using x-rays, but now, newer imaging methods, such as electron microscopy and magnetic resonance, are being used as well. The structures of the DNA, RNA, proteins that you have seen in many images are schematics that show the approximated positions of the atoms that form particular molecules. For example, Figure 1 shows the molecular structure of hemoglobin, the blood protein responsible for oxygen transport. Each protein subunit is shown in a different color. The red subunits are hemes and are the locations where oxygen binds to hemoglobin. These schematics, as well as the crystalline structures of molecules, are made from data obtained by x-ray crystallography as well as theoretical models based on atomic and molecular interactions. It was only in the later part of the twentieth century that advancements in atomic scale microscopy enabled us to visualize molecular structures and validate many theoretical models.

The many types of molecular imaging technologies provide great information about molecular structures, but cannot provide information about the genetic code contained by the DNA or RNA. Molecular imaging cannot be used to compare two segments of DNA to tell if they are identical or not. Gel electrophoresis, a method based on the motility of polarized molecules in agarose gel when an electric current is a technology that can be used to compare DNA segments and determine their molecular weight.

This lesson and its associated activity make an excellent complement to the typical lesson on DNA structure or protein and enzyme structure/function. The lesson is designed to have students inquire about molecular imaging, the physics concepts behind it, and about DNA gel electrophoresis. As part of the lesson, include a discussion and presentation of the structure of biomolecules and the arrangement of atoms inside the molecules.

As a discussion starting point, present simple examples, such as the water molecule shown in Figure 2, with its three atoms arranged in a tetrahedron configuration. Proteins and enzymes are very complex molecules made of other molecules called subgroups, which are, in turn, made of amino acids, which, in turn, consist of smaller molecules. The interactions between all the molecules that make up a protein result in highly complex molecular structures.

Based on the atomic and molecular interactions, four levels of molecular structure exist when describing the protein/enzyme structure (see Figure 3). The primary structure consists of the amino acid sequence that makes up a protein. The intermolecular interactions between the amino acids result in secondary structures that are further classified into beta sheets and alpha helices. The secondary structures also interact and result in more complex, tertiary and quaternary structures. The function of proteins/enzymes is highly dependent on the configuration of these structures and small alterations, such as adding, deleting or replacing one or more amino acids, can potentially result in defective proteins.

Conclude by introducing more complex molecular structures again, discussing the effect of atomic interactions of the molecular structures and how chemical models can predict the structure.

Artistic rendering of water molecule: H2O.
Figure 2. A water molecule has a simple molecular structure consisting of three atoms.
copyright
Copyright © 2012 London South Bank University http://www.lsbu.ac.uk/water/molecule.html
Diagrams of the four main protein structures levels: Primary structure (amino acid sequence) , secondary structure (regular sub-structures, such as alpha helix and beta sheet), tertiary structure (three-dimensional structure, such as P13 protein), and quaternary structure (complex of protein molecules, such as hemoglobin).
Figure 3. The complex molecular structure of proteins is divided into four structural levels.
copyright
Copyright © 2008 LadyofHats, Wikipedia http://en.wikipedia.org/wiki/File:Main_protein_structure_levels_en.svg

Associated Activities

  • Inside the DNA - Students conduct research to learn about the engineering technology methods used by scientists to analyze or validate the molecular structure of DNA, proteins and enzymes, and basic information about electrophoresis and DNA identification. They share their findings through 10-slide class presentations.

Assessment

For a summary assessment of the lesson and its associated activity, see the Assessment section in the activity write-up for suggested criteria to use to evaluate student presentations on specific imaging technologies.

Additional Multimedia Support

Find protein and enzyme structure images at the RCSB Protein Data Bank database: http://www.rcsb.org/pdb/home/home.do

Contributors

Mircea Ionescu; Myla Van Duyn

Copyright

© 2013 by Regents of the University of Colorado; original © 2012 University of Houston

Supporting Program

University of Houston, National Science Foundation GK-12 and Research Experience for Teachers (RET) Programs

Acknowledgements

This digital library content was developed by the University of Houston's College of Engineering under National Science Foundation GK-12 grant number DGE-0840889. However, these contents do not necessarily represent the policies of the NSF and you should not assume endorsement by the federal government.

Last modified: September 5, 2017

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