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Using Technology to Study

Cellular and Molecular Biology

under a contract from the

National Institutes of Health

National Center for Research Resources

5415 Mark Dabling Boulevard

Colorado Springs, Colorado 80918

BSCS Development Team

Design Conference Participants

Rodger Bybee, Principal Investigator

Philip Bourne, University of California San Diego, La Jolla,

Jerry Phillips, Project Director

California

April Gardner, Curriculum Developer

David Gorenstein, University of Texas Galveston, Galveston, Texas

Sharmila Basu, Curriculum Developer

Amy Lee, King Kekaulike High School, Pukalani, Hawaii

Carrie Hamm, Project Assistant

Maryann Martone, University of California San Diego, San Diego,

Ted Lamb, Evaluator

California

Barbara Perrin, Production Director

Joe Matteson, Pojoaque High School, Santa Fe, New Mexico

Ric Bascobert, Editor

Alexander McPherson, University of California Irvine, Irvine,

Diane Gionfriddo, Photo Research

California

Lisa Rasmussen, Graphic Designer/Illustrator

Kim Noethen, Pine Crest Preparatory School, Fort Lauderdale,

Florida

BSCS Administrative Staff

Howard Robinson, Brookhaven National Laboratory, Upton,

Carlo Parravano, Chair, Board of Directors

New York

Rodger W. Bybee, Executive Director

Michael Schmid, Baylor College of Medicine, Houston, Texas

Pam Van Scotter, Director, Curriculum Development Center

Rich Wasserman, Sand Creek High School, Colorado Springs,

Janet Carlson Powell, Associate Director, Chief Science

Colorado

Education Officer

Leigh Yarbrough, Cimarron High School, Cimarron, New Mexico

Larry Satkowiak, Associate Director, Chief Operating Officer

Primary Field-Test Teachers

National Institutes of Health

Patrick Beohmer, Carrington Public Schools, Carrington,

Krishan Arora, Health Scientist Administrator, National Center

North Dakota

for Research Resources

Patricia Carothers, Monte Vista High School, Danville, California

Bruce Fuchs, Director, Office of Science Education

Carlos Charriez, Northwest High School, Germantown, Maryland

William Mowczko, Project Officer, Office of Science Education

Brenda Chenier, Eastern Senior High School, Washington, District

Cindy Allen, Editor, Office of Science Education

of Columbia

Lisa Strauss, Project Officer, Office of Science Education

Carol Johnson, John Jay Science Academy, San Antonio, Texas

Amy Lee, King Kekaulike High School, Pukalani, Hawaii

Edge Interactive Staff

Catherine Ratliff, Lafayette County High School, Oxford,

Bruce Surgenor, Senior Project Manager

Mississippi

Terry Wallace, Senior Project Manager

Ann Sisson, Southern High School, Racine, Ohio

George Rosales, Art Director

Carol Wheeler, Pine Creek High School, Colorado Springs,

Bill Bolduc, Software Development Manager

Colorado

Greg Banse, Multimedia Engineer

Eric Reinhart, Multimedia Engineer

Secondary Field-Test Teachers

Dawn Emanuel, Sallisaw High School, Sallisaw, Oklahoma

Keith Gibbons, Catholic Central High School, London, Ontario,

SAIC Staff

Canada

Bach Nguyen, Project Manager

Terry Houchens, Joliet Central High School, Joliet, Illinois

Steve Larson, Web Director

Patrick Kosher, Cornell High School, Cornell, Wisconsin

Doug Green, Project Lead

Alan Wasmoen, Mt. Michael Benedictine School, Elkhorn, Nebraska

Tommy D’Aquino, Multimedia Director

Paul Ayers, Multimedia Developer

Cover Illustration

John James, Multimedia Developer

The structure of the oncogene H-Ras p21 protein complexed with

Jeff Ludden, Multimedia Programmer

GTP on the cover photograph was taken from the Protein Data

Pat Leffas, Multimedia Programmer

Bank (PDB) ( http://www.pdb.org), protein number PDB ID: 121P.

Aaron Bell, 3D Animator

(Source: Wittinghofer, F., U. Krengel, J. John, W. Kabsch, E.F. Pai.

David Kirkpatrick, Graphic Designer

1991. Three-dimensional structure of p21 in the active conforma-

Dave Nevins, Audio Engineer/Senior Web Developer

tion and analysis of an oncogenic mutant. Environmental Health

Jessica Butter, Senior Web Developer

Perspectives, 93: 11.)

Katie Riley, Web Developer

James Chandler, Web Developer/Usability Specialist

This material is based on work supported by the National Institutes

Abdellah Bougrine, Web Developer/Section 508 Specialist

of Health under Contract No. 263-00-C-0039. Any opinions, find-

Ginger Rittenhouse, Web Developer/Quality Assurance

ings, conclusions, or recommendations expressed in this publica-

Mary Jo Mallonee, Web Developer/Editor

tion are those of the authors and do not necessarily reflect the view

of the funding agency.

Advisory Committee

Yury Chernoff, Georgia Institute of Technology, Atlanta, Georgia

Copyright © 2005 by BSCS. All rights reserved. You have the per-

Leemor Joshua-Tor, Cold Spring Harbor Laboratory, Cold Spring

mission of BSCS to reproduce items in this module for your class-

Harbor, New York

room use. The copyright on this module, however, does not cover

Sean Michael Kerwin, University of Texas, Austin, Texas

reproduction of these items for any other use. For permissions and

Loan Maas, High School Teacher, Longmont, Colorado

other rights under this copyright, please contact BSCS, 5415 Mark

Martin Shields, James Caldwell High School, West Caldwell,

Dabling Blvd., Colorado Springs, CO 80918-3842; www.bscs.org;

New Jersey

info@bscs.org; (719) 531-5550.

NIH Publication No. 05-5170

ISBN: 1-929614-14-4

Contents

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v About the National Institutes of Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii About the National Center for Research Resources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Introduction to Using Technology to Study Cellular and Molecular Biology . . . . . . . . . . . . . . . . . . . . . 1

• What are the Objectives of the Module?

• Why Teach the Module?

• What’s in It for the Teacher?

Implementing the Module . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

• What Are the Goals of the Module?

• What Are the Science Concepts and How Are They Connected?

• Science Content of the Lessons

• Conceptual Flow of the Lessons

• How Does the Module Correlate to the National Science Education Standards?

– Content Standards: High School

– Teaching Standards

– Assessment Standards

• How Does the 5E Instructional Model Promote Active, Collaborative, Inquiry-Based Learning?

– Engage

– Explore

– Explain

– Elaborate

– Evaluate

• How Does the Module Support Ongoing Assessment?

• How Can Controversial Topics Be Handled in the Classroom?

Using the Student Lessons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

• Format of the Lessons

• Timeline for the Module

Using the Web Site. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

• Hardware/Software Requirements

• Downloading and Installing Macromedia Flash Player

• Getting the Most out of the Web Site

• Collaborative Groups

• Web Activities for Students with Disabilities

Information about Using Technology to Study Cellular and Molecular Biology . . . . . . . . . . . . . . . 23

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

2 Major Preconceptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

3 Scale and Resolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

3.1 Scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

3.2 Resolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

4 Major Techniques in the Study of Cellular and Molecular Biology . . . . . . . . . . . . . . . . . . . . 26

4.1 Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

4.2 X-ray crystallography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

4.3 Nuclear magnetic resonance (NMR) spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . 33

4.4 Laser technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

4.5 Simulations and computations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

5 Technology and the Origins of Molecular Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

6 The Goal of This Supplement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

Student Lessons

• Lesson 1— What Is Technology? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

• Lesson 2— Resolving Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

• Lesson 3— Putting Technology to Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

• Lesson 4— Technology: How Much Is Enough? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

Masters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

Foreword

This curriculum supplement, from The NIH

ties promote active and collaborative learning

Curriculum Supplement Series, brings cutting-

and are inquiry-based to help students develop

edge medical science and basic research dis-

problem-solving strategies and critical thinking.

coveries from the laboratories of the National

Institutes of Health (NIH) into classrooms.

Each curriculum supplement comes with a

As the largest medical research institution in

complete set of materials for both teachers and

the United States, NIH plays a vital role in the

students, including printed materials, exten-

health of all Americans and seeks to foster

sive background and resource information,

interest in research, science, and medicine-

and a Web site with interactive activities. The

related careers for future generations. NIH’s

supplements are distributed at no cost to teach-

Office of Science Education (OSE) is dedicated

ers across the United States. All materials may

to promoting science education and scientific

be copied for classroom use but may not be

literacy.

sold. We welcome feedback from our users.

For a complete list of curriculum supplements,

We designed this curriculum supplement to

updates, availability and ordering information,

complement existing life science curricula at

or to submit feedback, please visit our Web site

both the state and local levels and to be consis-

at http://science.education.nih.gov or write to

tent with National Science Education Standards.1

Curriculum Supplements Series

It was developed and tested by a team com-

Office of Science Education

posed of teachers, scientists, medical experts,

National Institutes of Health

and other professionals with relevant subject-

6705 Rockledge Dr., Suite 700 MSC 7984

area expertise from schools and institutes from

Bethesda, MD 20892-7984

across the country; and by NIH scientists and

curriculum-design experts from Biological Sci-

We appreciate the valuable contributions of the

ences Curriculum Study (BSCS), Edge Inter-

talented staff at BSCS, Edge Interactive, and

active, and SAIC. The authors incorporated

SAIC. We are also grateful to the NIH scientists,

real scientific data and actual case studies into

advisors, and all other participating profession-

classroom activities. A three-year development

als for their work and dedication. Finally, we

process included geographically dispersed field

thank the teachers and students who partici-

tests by teachers and students.

pated in focus groups and field tests to ensure

that these supplements are both engaging and

The structure of this module enables teachers

effective. I hope you find our series a valuable

to effectively facilitate learning and stimulate

addition to your classroom and wish you a pro-

student interest by applying scientific concepts

ductive school year.

to real-life scenarios. Design elements include a

conceptual flow of lessons based on BSCS’s 5E

Bruce A. Fuchs, Ph.D.

Instructional Model of Learning, multisubject

Director

integration emphasizing cutting-edge science

Office of Science Education

content, and built-in assessment tools. Activi-

National Institutes of Health

supplements@science.education.nih.gov

________________________

1 In 1996, the National Academy of Sciences released the National Science Education Standards, which outlines what all citizens should understand about science by the time they graduate from high school. The Standards encourages teachers to select major science concepts that empower students to use information to solve problems rather than stressing memoriza-tion of unrelated information.

v

About the National Institutes of Health

Begun as the one-room Laboratory of Hygiene

• biological effects of environmental contami-

in 1887, the National Institutes of Health (NIH)

nants;

today is one of the world’s foremost medical

• understanding of mental, addictive, and

research centers and the federal focal point for

physical disorders; and

health research in the United States.

• collection, dissemination, and exchange of

information in medicine and health, includ-

Mission and Goals

ing the development and support of medical

The NIH mission is science in pursuit of funda-

libraries and the training of medical librari-

mental knowledge about the nature and behav-

ans and other health information specialists.

ior of living systems and the application of that

knowledge to extend healthy life and reduce the

Organization

burdens of illness and disability. The goals of

Composed of 27 separate institutes and centers,

the agency are to

NIH is one of eight health agencies of the Pub-

• foster fundamental creative discoveries,

lic Health Service within the U.S. Department

innovative research strategies, and their

of Health and Human Services. NIH encom-

applications as a basis for advancing signifi-

passes 75 buildings on more than 300 acres in

cantly the nation’s capacity to protect and

Bethesda, Md., as well as facilities at several

improve health;

other sites in the United States. The NIH budget

• develop, maintain, and renew scientific

has grown from about $300 in 1887 to more

resources—both human and physical—that

than $27.8 billion in 2004.

will ensure the nation’s ability to prevent

disease;

Research Programs

• expand the knowledge base in medical and

One of NIH’s principal concerns is to invest

associated sciences in order to enhance the

wisely the tax dollars entrusted to it for

nation’s economic well-being and ensure a

the support and conduct of this research.

continued high return on the public invest-

Approximately 82 percent of the investment is

ment in research; and

made through grants and contracts support-

• exemplify and promote the highest level

ing research and training in more than 2,000

of scientific integrity, public accountability,

research institutions throughout the United

and social responsibility in the conduct of

States and abroad. In fact, NIH grantees are

science.

located in every state in the country. These

grants and contracts make up the NIH Extra-

NIH works toward meeting those goals by pro-

mural Research Program.

viding leadership, direction, and grant support

to programs designed to improve the health of

Approximately 10 percent of the budget goes to

the nation through research in the

NIH’s Intramural Research Programs, the more

• causes, diagnosis, prevention, and cure of

than 2,000 projects conducted mainly in its

human diseases;

own laboratories. These projects are central to

• processes of human growth and development;

the NIH scientific effort. First-rate intramural

vii

scientists collaborate with one another regard-

trious scientists and physicians. Among them are

less of institute affiliation or scientific discipline

115 winners of Nobel Prizes for achievements as

and have the intellectual freedom to pursue

diverse as deciphering the genetic code and iden-

their research leads in NIH’s own laboratories.

tifying the causes of hepatitis.

These explorations range from basic biology to

behavioral research, to studies on treatment of

Five Nobelists made their prize-winning discov-

major diseases.

eries in NIH laboratories. You can learn more

about Nobelists who have received NIH sup-

Grant-Making Process

port at http://www.nih.gov/about/almanac/nobel/

The grant-making process begins with an idea

index.htm.

that an individual scientist describes in a writ-

ten application for a research grant. The project

Impact on the Nation’s Health

might be small, or it might involve millions of

Through its research, NIH has played a major

dollars. The project might become useful imme-

role in making possible many achievements

diately as a diagnostic test or new treatment, or

over the past few decades, including

it might involve studies of basic biological pro-

• Mortality from heart disease, the number

cesses whose clinical value may not be apparent

one killer in the United States, dropped by

for many years.

36 percent between 1977 and 1999.

• Improved treatments and detection methods

Each research grant application undergoes peer

increased the relative five-year survival rate

review. A panel of scientific experts, primarily

for people with cancer to 60 percent.

from outside the government, who are active

• With effective medications and psychother-

and productive researchers in the biomedi-

apy, the 19 million Americans who suffer

cal sciences, first evaluates the scientific merit

from depression can now look forward to a

of the application. Then, a national advisory

better, more productive future.

council or board, composed of eminent scien-

• Vaccines are now available that protect

tists as well as members of the public who are

against infectious diseases that once killed

interested in health issues or the biomedical sci-

and disabled millions of children and adults.

ences, determines the project’s overall merit and

• In 1990, NIH researchers performed the

priority in advancing the research agenda of the

first trial of gene therapy in humans. Scien-

particular NIH funding institutes.

tists are increasingly able to locate, identify,

and describe the functions of many of the

About 38,500 research and training applications

genes in the human genome. The ultimate

are reviewed annually through the NIH peer-

goal is to develop screening tools and gene

review system. At any given time, NIH supports

therapies for the general population for can-

35,000 grants in universities, medical schools,

cer and many other diseases.

and other research and research training institu-

tions, both nationally and internationally.

For more information about NIH,

visit http://www.nih.gov.

NIH Nobelists

The roster of people who have conducted NIH

research or who have received NIH support over

the years includes some of the world’s most illus-

viii

About the National Center for

Research Resources

The National Center for Research Resources

NIH-supported investigators and others special-

(NCRR) is a component of the National Insti-

ized research environments that are profession-

tutes of Health (NIH), one of the world’s fore-

ally staffed, have state-of-the-art technologies

most biomedical research organizations. The

and Web-based networks, and provide col-

institutes and centers that compose NIH fund

laborative research opportunities. NCRR also

biomedical research to uncover new knowl-

supports networks of National Gene Vector Lab-

edge that will lead to better health for everyone

oratories and Human Islet Cell Resource Cen-

in the nation. Among the NIH institutes and

ters, a resource for normal and diseased human

centers, NCRR has a unique role. Rather than

tissue for research, and science education for

supporting studies of specific diseases or dis-

K−12 students and the public.

orders, NCRR supports programs that ensure

that essential tools, materials, specialized facili-

Comparative Medicine: Animal models and

ties, and resources for infrastructure and man-

colonies (mammalian and nonmammalian),

power development are accessible to biomedical

genetic stocks, and biological materials—such

researchers throughout the nation. In this way,

as cell lines, tissues, and organs—help meet

NCRR enables research in many areas of health

NIH-supported investigators’ resource needs. In

and complements the missions of the NIH

particular, the NCRR network of eight National

categorical institutes. NCRR’s diverse array of

Primate Research Centers is a valuable resource

resources is concentrated in four divisions:

for investigations of human health and disease.

Biomedical Technology Research and Research

Research Infrastructure: Diverse grant programs

Resources: A large network of Biomedical Tech-

help build, expand, and strengthen the nation’s

nology Resource Centers provides the research

biomedical research environment by developing

community nationwide with the newest and

research infrastructure and faculty capacity at

most advanced technologies and techniques.

minority institutions that award doctorates in

Core scientists at these centers collaborate in

the health or health-related sciences; improving

multidisciplinary investigations and train vis-

biomedical and behavioral research through an

iting researchers to apply these technologies

NIH-wide program of matching grants for con-

and techniques to basic and clinical studies. In

struction and renovation of research facilities;

addition, NCRR provides institutional grants to

and increasing competitiveness of institutions

purchase expensive state-of-the-art and high-

from states with limited NIH support.

end instrumentation to be used by a number of

investigators on a shared basis.

For more information about research resources

and resource-related funding opportunities, visit

Clinical Research Resources: A national network

the National Center for Research Resources Web

of General Clinical Research Centers offers

site at http://www.ncrr.nih.gov.

ix