BQ Notes Template...burst the “dot-com” bubble and a competitive search for an alternative to attract funding and attention was on. One attractive alternative, referred to as “Cracking

Vol. 13(1) Spring 2004 BioQUEST Notes Page 1

BioQUEST NotesVolume 13 Number 1 A publication of the BioQUEST Curriculum Consortium Spring 2004

I tems Of Special Interest In This Issue:Systems Biology: BioQUEST Summer 2004 Workshop ................................................................................ 1Problem Spaces and BioQUEST: Finding ways to support inquiry ............................................................. 1Announcements ................................................................................................................................................... 2New BEDROCK Web Site ................................................................................................................................... 3LifeLines OnLine and Case-Based Learning ................................................................................................... 4Case It! Simulation Keeps Expanding ............................................................................................................. 10

Analysis Tools

Data Sets

BiologicalPrinciples

Problem Space

Ever since the human genome was sequenced, specula-tion about the next big challenge has captivatedattention. For a while it appeared that “biotechnology”would capture the funding field. However, overinflatedexpectations of venture capitalists and stockholdersburst the “dot-com” bubble and a competitive search foran alternative to attract funding and attention was on.One attractive alternative, referred to as “Cracking theSecond Genetic Code” or “Big Blue,” was a massivecampaign to solve the three-dimensional structure ofevery protein in a human body. This initiative wouldemploy X-ray crystallography, NMR spectroscopy, andprediction from primary structures to attempt themassive task.

Another strong contender is an emerging area calledsystems biology. Among the signposts of the magni-tude and tenacity of this new movement are:• the establishment of a Systems Biology department as

“the first entirely new department in 20 years” atHarvard University (Check, 2003);

• a five-year, $16 million grant from the NationalInstitutes of Health to MIT to improve understandingof biological control circuits through analysis andcomputational modeling of overall systems (TechTalk, 2003);

This issue of BioQUEST Notes contains a suite of fourarticles exploring the concept of a “problem space.” Thearticles illustrate how BioQUEST is using the notion of aproblem space to provide a conceptual field where re-searchers—student and teacher alike—can pursue a line ofinvestigation using rich, dynamic, and interdisciplinarymaterial in a collaborative context.

At its simplest level, the problem space is a way of organiz-ing diverse kinds of information and tools to supportinquiry. This information includes background materialthat grounds the problem with biological principles,existing (and sometimes extensive) data sets providingraw material for analysis andinference, and analysis toolsenabling the handling ofpreexisting and newlygenerated data.

The first article in thisset provides a pedagogi-cal overview of how thistool can be used and itsimplication in research,learning and teaching andhow it can support BioQUEST’s 3P approach to learningand teaching. The following articles introduce three ofBEDROCK’s current problem spaces— HIV evolution, TrpCage protein structure, and the chimpanzee as an endan-gered species.

continued on page 14continued on page 6

Systems BiologyEducation:Where 3PsMeets 3Ps

John R. Jungck

Robin M. Greenler

Problem Spaces andBioQUEST:

Finding ways to support inquiry


BioQUESTConsortium News

Announcements

Claudia Neuhauser has recently been named head of the Department of Ecology, Evolution, and Behavior (EEB) at theUniversity of Minnesota, College of Biological Sciences. She serves as EEB’s Director of Graduate Studies and last yearreceived the Stanley Dagley-Samuel Kirkwood Undergraduate Education Award for her course and textbook “Calculusfor Biology and Medicine.”

Ken Brown was a finalist in the prestigious Australian Awards for University Teaching which celebrate and rewardexcellence in university teaching. This joins several teaching awards that he has received from his home institution, TheUniversity of Technology Sydney.

Stacey Kiser has joined BioQUEST in Beloit during her six month sabbatical from Lane Community College in Eugene,Oregon. She is splitting her time teaching and working with the BEDROCK Project. The President of the NationalResearch Council recently appointed John Jungck to a six-year term on the U.S. National Committee for the Interna-tional Union of Biological Sciences (USNC/IUBS). The USNC/IUBS works with the International Council for Scienceto promote international collaboration in the biological sciences by working with professional societies in the UnitedStates to encourage U.S. scientists to participate in international activities. Marion Fass was recently elected Chair-Elect of the Undergraduate Faculty Section of the American Society of Microbiology. Sam Donovan, as director of theBEDROCK Project, is still very much involved in BioQUEST; however, his new position teaching in the School ofEducation at University of Pittsburgh is certainly providing some new opportunities. John and Robin Greenlerrecently returned from Tanzania, East Africa, directing the Associated Colleges of the Midwest Tanzania Program. Theyguided 19 undergraduates from nine midwestern colleges in the development, actuation and presentation of independentfield research projects in biology, anthropology and archeology.

It is with deep sadness that we share news of the loss of a member ofthe BioQUEST Consortium, Keith Stanley. Keith was an organicchemist at A.E. Staley Manufacturing Co., one of the largest cornrefiners in the United States. He was a contributor to BioQUEST’srecently published book, Microbes Count!, co-authoring the chapter,Searching for Amylase, and to the BioQUEST Library with hismodule, Looking into Glycosidases. Both pieces were developed withhis wife and partner Ethel Stanley. Keith and Ethel worked in separateprofessional circles, he drawing national attention as a senior re-searcher in carbohydrate chemistry, and Ethel as the director ofBioQUEST. However their BioQUEST collaborations reflected thedeeper intellectual and personal partnership that lent support andvitality to their lives, professionally and personally.

Keith will be missed.


If you’re one of the 5,000 repeat visitors to the BioQUESTweb site in the past year – or one of the 819 who have visitedmore than 10 times in the past six months, you’ve probablystumbled upon the new BEDROCK (Bioinformatics Educa-tion Dissemination: Reaching Out, Connecting, and Knit-ting-together) site. It launched September 13, 2003 – but thisis our first formal announcement and introduction to its datadriven features.

We hope this website will capture your interest and sparkcollaboration in the ongoing exploration of bioinformatics forthe classroom. The core of the site is the Problem Space —an area currently undergoing rapid development. (See articlestarting on page 1.) You will also will find information aboutproject staff, links to bioinformatics tools and web sites,publications, projects,and bioinformatics

degree programs. Finally, we promote our own BEDROCK workshops (a major aimof our NSF grant) as well as other events that our staff members attend as partici-pants or presenters.

Many elements of the site are “dynamically driven” – posted to your browser out of avariety of databases. This includes calendar information, degree programs, and the“tidbits” of information that appear on each page below the navigation bar. Tidbitsare selected items of general interest (meetings, conferences, web sites) as well asitems relevant to specific Problem Spaces (papers, etc.). We encourage you to usethe Feedback link to submit items for display in the “tidbits” area.

There are two other technologicalelements that are new to both the BEDROCK and the main BioQUESTsites. The first is online event registration that submits directly into ourdatabases. The second feature is an online project submission processutilized during workshops to gather real-time curriculum innovation byparticipants. If you explore the Resources pages of past workshops, youwill see these submissions. Soon we will display gems of these collabora-tive explorations in a central location.

We hope you will explore the site soon – and repeatedly – over the nextfew months as we develop some additional features:• User registration that allows you to opt-in to BQ email announce-ments, access upcoming interactive/collaborative features of the site;• Search capabilities;• Curricular Resource Submissions enabling you to share yourclassroom innovations via an online submission form. These itemscould be syllabi, lecture notes, PowerPoint presentations, studentposters, images, or data;• Separation of general links from links to software tools into a datadriven, enhanced format;• Creation of a “catalogue” of recommended bioinformatics books;• Continued development of “collaboratory” features such as usersubmission of website material such as books, links, tidbits, and tools.

BEDROCK Launches New Website

Warning:In order to improveBioQUEST.org site, many “old”pages will be archived. We areactively viewing usage logs toavoid deleting pages in demand.However, if you discover abroken link to an old “BQ”favorite, please [email protected].

Amanda Everse

http://www.bioquest.org/bedrock


BioQUEST’s LifeLines OnLine (LLOL) Project is now inits 5th year. As a project of the BioQUEST CurriculumConsortium, LLOL Project’s core pedagogical philosophyis thoroughly congruent with BioQUEST’s notion ofcurricular reform through authentic student-led inquiry.However, LLOL utilizes the specific approach of Investi-gative Case-Based Learning (ICBL) to charge up scienceclassrooms and even online courses. For those of you whohave not yet become involved with LifeLines OnLine, anoverview of the particulars of the program and of ICBLmight be of interest.

ICBL is a variant of Problem-Based Learning that empha-sizes student investigations. Investigative case-basedlearning begins by providing students with short, realisticnarratives (i.e. the cases) about people dealing withscience-related situations, such as:• investigating the spread of West Nile Virus;• controlling gull populations at airports;

• conserving food-stained artifacts;• identifying illegal whale meat products;

LifeLines OnLine and Investigative Case-Based Learning:A Powerful Approach to Inquiry-Based Learning

Margaret Waterman

• exploring potential impacts of increased caffeine levelsin fresh water habitats;

• considering the technology behind geneticallyengineered pharmaceuticals.

By working with such cases, students learn biology inmeaningful contexts as they employ scientific informationand methods to investigate these realistic and complexsituations. Multiple research studies of case-basedlearning show that when learning occurs around a realproblem, there is an increase in both retention of informa-tion and in the ability to apply concepts to similar situa-tions.

The three phases in ICBL parallel BioQUEST’s “3 Ps” ofproblem posing, problem solving and peer persuasion. InICBL, during the first phase, students read the case andthen work collaboratively to complete a Case Analysis.By methodically analyzing the cases, the students begin tostructure their own learning of both science process andcontent. Students recognize the value of their own priorknowledge as well as that of their peers. At the same time,they identify areas they need to learn more about and theresources they will use for that learning.

During ICBL’s second Problem Solving phase, studentsdefine and undertake investigations in which they useobservational skills, propose hypotheses, design experi-ments, gather data, use models, interpret graphs, andsupport their conclusions with evidence. In the last phaseof ICBL, Peer Persuasion, they present their findings toothers using a wide variety of potential formats.

LifeLines OnLine runs workshops around the country.The next workshop is featured at a Chautauqua shortcourse this summer, July 11-13, 2004 in Memphis,Tennessee. (See next page.) It will be a great opportunityto experience this form of Problem-Based Learning first

hand.

Lifelines Cases focus on a widerange of science-related situations.


led by LifeLines Project DirectorsMargaret Waterman , Southeast Missouri State University and

Ethel Stanley, BioQUEST at Beloit College

Participants in this very interactive course will:• Try out investigative case-based learning;• Explore online investigative case modules developed by faculty from over sixty

different institutions and departments;• Use computational tools and modeling to investigate biological problems;• Develop their own case module;• Access web-based biology materials for their own courses;• Plan for implementation and assessment of student learning in their own classrooms.

Prerequisites:Participants should bring a syllabus for a course in which they would like to develop one or more cases. Basic familiar-ity with preparing electronic documents (word processing) and with using web browsers and web searching is assumed.No special knowledge of any other software is required. All costs, excluding travel, are paid by the National ScienceFoundation.

Additional information and application materials are available athttp://www.cbu.edu/~edoody/course_list.htm

For:• Biologists and chemists interested in incorporating bioinformatics into their curricula• Mathematicians and computer scientists curious about how their fields impact bioinformatics or computational

molecular biology

How does an evolutionary perspective inform structural biology?Building the Links in Bioinformatics Education

Additional information and application materials are available athttp://www.bioquest.org/bedrock/san_diego_05_04/

This course will focus on several different ways that the analysis of molecular data is being applied to examinecurrent issues such as evolution of disease, molecular structural biology, phylogeography, and conservation. The relation-ships between evolutionary theory and the analysis of molecular sequence and structure data will be addressed. Thediscussions will focus on how to analyze data, how to implement bioinformatics investigations across the curriculum,and how to develop sustained collaboration.

LifeLines OnLine, Chautauqua Short Course July 11-13, 2004 Memphis, TN

For:• College teachers of biology, environmental science, chemistry, or geoscience• High school science teachers of advanced courses are welcome if space is available

May 20 - 23, 2004San Diego Super Computer Center,

University of California, San Diego, CAled by:

John R. Jungck, Rama Viswanathan, and Tony Weisstein, Beloit CollegeSam Donovan, University of Pittsburgh

Rebecca Roberts, Ursinus College


Corn Borer lifecycle,George Heimpel,University of Minnesota,Dept. of Entomology

• the formation of the International Conference onSystems Biology at Cal Tech (www.icsb2001.org/);

• Leroy Hood’s establishment of the Institute for SystemsBiology, a nonprofit research institute dedicated to thestudy and application of systems biology.

Several year ago we began planning a 2004 BioQUESTCurriculum Consortium summer workshop to focus onsystems biology education. During the intervening years,systems biology departments, institutes, and companieshave been founded; however, as of now, we don’t have the

usual educational materials that we expected. Where arethe syllabi, textbooks, laboratory exercises, software, andweb sites on systems biology education? That gap willafford us considerable opportunity for original work at the19th annual BioQUEST Curriculum Development summerworkshop. This new discipline of systems biology willobviously affect most biology departments and affordmany career possibilities for our students. We hope theBioQUEST workshop will lay a foundation for an educa-tional approach to this new discipline.

continued on next page

The “synergistic integration oftheory, computation, andexperiment” is drawn fromnetworks at the molecular tothe landscape levels.

Panthothenate metabolicpathway as depicted onBioGrapher software, RamaViswanathan, Beloit College

from page 1Systems Biology

Malaria life cycle, Center forDisease Control and Prevention,http://www.dpd.cdc.gov

Logging system model fromEnvironmental DecisionMaking software, E. C. andH. T. Odum

Rabies cycle of infection andreplication, National Center forInfectious Diseases, http://www.cdc.gov/ncidod


A Proliferation of “Ps”In his IMA Public Lecture, “After the HumanGenome Project: Systems Biology and Predictive,Preventive and Personalized Medicine,” LeroyHood cites the ability of systems biology to movefrom genotype to phenotype and to apply that tomedical diagnosis, prognosis, and amelioration ofdisease. He promises that systems biology willdeliver a “Personalized, Predictive and PreventativeMedicine.” (See table below.) Similarly, theHoward Hughes Medical Institute used 3Ps to catchreader interest in the article “Persistence, Persever-ance and Patience at the Bench” (Howard HughesMedical Institute 2003). An engineer calledsystems biology “Pathways, Proteomes, and Programs;”and a business writer, “Promises, Perils, and Profits.” Inaddition to their own versions of the “3 Ps,” all four shareseveral commonalities in heralding this new biology. Theyagree that systems biology will:• be highly interdisciplinary, drawing upon biology,

mathematics, computer science, engineering andtechnology;

• require collaborative teams rather than individuals;• be antireductionistic, involving extensive modeling,

visualization, and massively parallel computing tointegrate vast quantities of data into synthetic schemes.

For over twenty years, the BioQUEST CurriculumConsortium has promoted our 3 Ps of problem posing,problem solving, and peer persuasion. BioQUEST’sapproach dovetails well with the three characteristics ofsystems biology above in that:1. We have maintained an interdisciplinary community

from the beginning; the founding group of eighteenpeople included biologists, science educationresearchers, cognitive psychologists, computerscientists, mathematicians, historians and philosophersof science, and an architect. This heterogeneity isevident in the composition of contributors to TheBioQUEST Library and among participants of theannual curriculum development workshops.

2. Collaborative learning has been a core component ofboth our philosophy of pedagogy and in thedevelopment of computer software and investigativecases.

3. Systems thinking and synthesis has been a part ofBioQUEST from its inception. Initially, theConsortium was primarily grounded in evolutionarybiology that has a strong basis in doing synthetic work.Furthermore, H.T. Odum, one of the founders ofsystems ecology, was also a contributor to the first

volume of The BioQUEST Library and was active andinfluential in the Consortium throughout the remainderof his life.

Systems biology has been associated with educationalinitiatives since its inception. We feel that there are naturalsynergisms between the contemporary development ofsystems biology and BioQUEST’s heritage, mission, andtrajectory. For example, the Institute for Systems Biologyhas a large outreach program in the Seattle area for 1,300K-12 educators from 105 schools and their students. Theywant to turn students on to the excitement of a hot newfield full of promise for health and agriculture, to thepotential careers, and to the difficult ethical and legalissues that we will face around issues such as fetal stemcell cloning, genetic privacy, genetically modified foods,and extended lives. Furthermore, they explicitly promoteinquiry-based learning, extensive use of technology,professional teacher preparation and in-service education,and systemic reform. Thus, they are natural partners. Wehave already discussed future collaborative activities withPatrick Ehrman, the director of the Institute for SystemsBiology’s educational outreach program.

ChallengesIf systems biology is “characterized by a synergisticintegration of theory, computation, and experiment”(International Conference on Systems Biology, Cal Tech,www.icsb2001.org), then a principal challenge in the fieldis making sense of massive amounts of data arising frommicroarray analysis of millions of experiments. In thewords of the recognized founder of the discipline, LeroyHood, President of the Institute for Systems Biology inSeattle,

“Systems biology is a unique approach to the study of

genes and proteins which has only recently been made


from previous pageSystems Biology

Application of Systems Biology Approach to Medicine

Predictive

• probabilistic health history—DNA sequence

• biannual multiparameter blood measurements

Preventative

• design of preventative measures via systems approaches

Personalized

• unique human variation mandates individual treatment

from Leroy Hood, Institute for Systems Biology, www.systemsbiology.org/


possible by rapid advances in

computer technology. Unlike

traditional science which examines

single genes or proteins, systems

biology studies the complex

interaction of all levels of biological

information: genomic DNA, mRNA,

proteins, functional proteins,

informational pathways and

informational networks to

understand how they work together.”

(Ideker et al. 2001).

Certainly this new discipline will beextraordinarily interdisciplinary involv-ing biologists, computer scientists,mathematicians, and engineers. Not only will experimentalbiology change by the use of nanotechnology, robots, andartificially intelligent machines, the role of modeling willplay a much larger role in systems biology than everbefore. We will be “inundated with information, butstarving for knowledge” to use David Shenk’s famousphrase (Shenk 1997). The need for new highly integratedmodeling environments, data mining, massively parallelcomputing, multivariate statistics, and multidimensionalvisualization will be as important as the hardware em-ployed in the lab.

BioQUEST 2004 Summer WorkshopOur BioQUEST 2004 Summer Workshop will examinehow we begin to build an educational strategy for teachingsystems biology, given all of these challenges. Someguiding questions include:• How can we prepare our students to work on such

challenging problems in such heterogeneouscollaborations?

• What tools exist now that we can use to have studentsexplore systems biological thinking and do these sortsof analysis?

• How will systems biology fit into current courses andwhat new courses will be helpful?

This summer we are extremely fortunate to have fivespeakers who are software developers as well as leadingspokespersons for the new field of systems biology. Theworkshop will lead off with Professor Herb Sauro whowill introduce us to systems biology with his speech,“Understanding Cellular Networks through Modeling andAnalysis.” Dr. Sauro is currently a faculty member atClaremont’s newest college, the Keck Graduate Institute,where he teaches and carries out research in computationalsystems biology. Originally from the UK, Dr. Sauro

obtained degrees in Biochemistry and Microbiology. Hesubsequently moved to Edinburgh to work with Dr. HenrikKacser where he continued to develop metabolic controlanalysis. Subsequently he changed careers to become ahigh school science teacher. Three years later he started acompany that specialized in developing and marketingeducational software and eventually moved into financialsoftware development at GE and the Financial Times. Atthe time, there was a growing interest in the US to studysystems biology and he returned to academia by acceptingan offer from Caltech to assist in the development of theSystems Biology Markup Language. From Caltech hethen moved on to the Keck Graduate Institute. After histalk he will also demonstrate his software JDesigner(www.cds.caltech.edu/~hsauro/JDesigner.htm) in aninteractive lab.

The keynote speaker this year is James B. Bassing-thwaighte, M.D., Ph.D., whose title is: “The Eternal Cell.”A professor in the Bioengineering Department at theUniversity of Washington, Dr. Bassingthwaighte is theoriginator of the “Human Physiome Project,” a large-scale,international program for understanding genomic andpharmaceutical effects on human physiology through thedevelopment of databases and biological systems model-ing. Other work includes the “Cardiome Project,” whichdeals with defining a functional heart in mathematicalterms (http://nsr.bioeng.washington.edu/~jbb/). Dr.Bassingthwaighte contends that “this new physiome



Dr. Herb Sauro, developer of the JDesigner software,will speak on “Understanding Cellular Networksthrough Modeling and Analysis.”


paradigm, if we attempt to legitimize it by giving it a namethat implies an integrative approach, is this: to recognizethat biological, ecological, atmospheric and other systemsbehave in patterns” (Bassingthwaighte 2000). Dr.Bassingthwaighte will lead a full session on dynamicmodeling of physiological systems on the following day.

Part of systems biology has involved the intensive use ofDNA arrays to study gene expression and its impact onmetabolic pathways. In addition to Professor Sauro’sJDesigner, we will highlight three other packages forhandling such data and introducing participants into theextensive use of graph theory for visualization andanalysis of complex interactions. First, Dr. Kam Dahlquist,a professor in the Vassar College Biology Department, willpresent on the GenMAPP software, a tool for viewing andanalyzing microarray data in terms of up- and down-regulation of biochemical pathways (www.GenMAPP.org).She led development of GenMAPP when she was apostdoctoral fellow at the Gladstone Institute of Cardio-vascular Disease in San Francisco (http://biology.vassar.edu/dahlquist.html). She will be joined bytwo Beloit College Professors, Rama Viswanathan,Chemistry and Computer Science, and John R. Jungck,

Biology, who have developed BioGrapher using TomSawyer’s Graph Layout engine to study networks inmetabolic pathways such as those from the KEGGdatabase and JavaBENZER. JavaBENZER is an extensionof The BioQUEST Library package BENZER that ishelpful for analyzing interval graphs applied to patterns ofgene expression in microarray data.

Later in the week, Ivan Ovcharenko, Ph.D., a bioinformat-ics scientist at the Lawrence Livermore National Labora-tory in California, will present on comparative genomics.

He is the developer of three major softwarepackages for post-genomic bioinformatics:CRÈME, zPicture, and eShadow. He will give ageneral overview of comparative genomics,demonstrate tools for genome data mining, andhelp participants develop strategies for characteriz-ing noncoding elements of vertebrate genomes(http://ivan.dcode.org/). Also joining us will beWayne Matten from The National Center forBiotechnology Information of the U.S. NationalLibrary of Medicine, who will be offering aworkshop on new tools that they have available forpublic use in computational molecular biology andbioinformatics (http://www.ncbi.nlm.nih.gov).

In addition to these leaders in systems biology,other speakers will focus on education per se.BioQUEST staff, Ethel Stanley, Stacey Kiser, John

Greenler, and Robin Greenler will lead workshops innetwork analysis across biological levels (from molecularto ecological), systems ecology simulations, and frag-mented ecosystem analysis from a biocomplexity perspec-tive.

Making ConnectionsSystems biology is both exceptionally new and has beenaround for most of a century. Ludwig von Bertalanffywrote on a systems approach for almost 50 years startingin 1928. He is generally considered to be the foundingfather of the General System Theory and publishednumerous books and articles including, Kritische Theorieder Formbildung, (Modern Theories of Development, AnIntroduction to Theoretical Biology) (von Bertalanffy1928) and Theoretische Biologie (von Bertalanffy 1932,1940). Bertalanffy conceived clearly enough how interac-tive relationships may dynamically maintain diverse kindsof wholes (systems). He further developed the hypothesisthat has been allowing the discovery of laws of organiza-tion, those that govern the functioning of different kinds ofsystems (www.bertalanffy.org/sites/index1.htm).


continued on page 13

Dr. JamesBassingthwaightewill provide thekeynote addressentitled, “TheEternal Cell.”


The Case It! project has come a long way since it was firstconceived at the 1995 BioQUEST summer workshop(Klyczek and Bergland 1996). At that time we haddeveloped a DNA electrophoresis simulation as part of anNSF CCD-funded project, and during the workshop ourgroup decided to generate case studies that would use thesimulation software for DNA testing to analyze the cases.The DNA electrophoresis simulation became part of theBioQUEST Library with Vol. IV (Bergland and Klyczek1998; Bergland et al. 2001). We subsequently received anadditional NSF-CCLI grant to further develop the Case It!project, which now includes an enhanced version of thesimulation software, an electronic resource manual, and anintegrated web page editor and internet conferencingsystem. The newest version of the software, as well astutorials, access to the web editor, and results of classtesting, is available on the Case It! home page, http://www.uwrf.edu/caseit/caseit.html. The software can bedownloaded free of charge for educationaluse.

We have demonstrated the software atnumerous workshops and presentations,including NABT, NSTA, ACUBE, andABLE (Bergland et al. 1999), and biologyeducators around the world have used it intheir classes. In our introductory biologyclasses at UW-River Falls, we haveemphasized human genetic disease casesbecause of the high degree of studentinterest in these cases and ethical issuesthat make them particularly well suited forspirited discussion and debate. Studentsfirst play the roles of laboratory techni-cians as they analyze DNA sequencesassociated with particular cases andconstruct web page posters giving resultsof genetic testing. They then play the rolesof genetics counselors and family membersas they ask and answer questions concern-ing these tests.

Case It! v. 4.02 is the current version of thesimulation software, and it includes

Case It! Case-based learning via simulations of molecularbiology techniques and internet conferencing

Karen K. Klyczek and Mark S. BerglandBiology Department

University of Wisconsin-River Falls

Mary A. LundebergDepartment of Teacher Education

Michigan State University

restriction enzyme digestion, electrophoresis, Southernblot (Fig. 1), PCR, and dot blot. It is completely open-ended, in that any DNA sequence can be analyzed. Thesimulation reads data as text files representing DNAsequences, restriction enzyme recognition sites, probes,and primers. Included with the software are DNA se-quences associated with various case scenarios, along withthe appropriate restriction enzymes, probes, or primersnecessary to analyze the case. Cases developed and class-tested to date include Alzheimer’s disease, breast cancer,sickle-cell disease, muscular dystrophy, cystic fibrosis,phenylketonuria, Huntington’s disease, and fragile-Xsyndrome. These DNA sequences were obtained from theGenBank database and modified to create multiplescenarios involving hypothetical family members beingtested for the presence of disease mutations.

Fig. 1: Lab Bench screen of the Case It! Simulation showing Southernblot results of one scenario from the sickle-cell case.



Students use Case It! Investigator, a separate softwaremodule, to provide background information about thecases. This software contains an electronic version of theresource manual, with case scenarios and instructions forusing the simulation software. In addition, when studentsclick links or use the button bar to access pull-down menusof links (Fig. 2), Investigator will automatically open theirweb browser to those Internet sites, and keep track of themfor future reference. Investigator will also open anyapplication on the user’s hard drive, including otherBioQUEST modules useful for case analysis. Instructorscan easily change links, menu items, button names andtextual content by changing the content of simple text andhtml files that are automatically read each time Investiga-tor starts.

Once they have gathered background information, studentsuse the Case It! simulation to run analyses for DNAsequences associated with their particular case. They thencreate posters describing their analysis using a custom webpage editor accessible from the Case It! Launch Pad. Thiseditor enables students to easily add and edit the varioussections of their web pages and to incorporate gel/blotphotos and other images. Text and graphics are automati-

cally uploaded to a central server located at the Universityof Wisconsin-River Falls. The Launch Pad also organizeslinks to each group’s discussion forum and published webpage, and provides a feature for compiling messages sentby individual students. The integrated web page editor/conferencing system is designed for ease of use, even ifstudents have had no prior experience building web pagesor conferencing. Students play the role of geneticscounselors when responding to questions sent to their owngroup’s forum; they play the role of family memberswhen sending messages to other groups’ forums.

Class testing has involved pre-service science teachers invideotaping, observing and interviewing students as theyuse Case It! computer modules. The results of five years

of class testing demonstratedthat students developed moreconfidence in their under-standing of genetic testing,became more aware of theethical dimensions of howsuch scientific problemsaffect society, and connectedcontent in a required intro-ductory science course witheveryday life (Lundeberg etal. 2002, 2003; a summary isalso available at http://www.uwrf.edu/caseit/PathwaysMB2.html).

We have just received a newNSF-CCLI grant to expandthe project to include open-ended simulations of proteinanalytical methods, such asELISA and Western blot.These new features will allowdevelopment of cases basedon infectious diseases ofhumans and domesticanimals, such as HIV/AIDS,

influenza, anthrax, and West Nile, among many others.We welcome suggestions for specific cases or for featuresto incorporate into the new modules.

Educators wishing to involve their students in the Case It!project, at no cost, should visit the Case It! home page(http://www.uwrf.edu/caseit/caseit.html) or [email protected] for details.

Fig. 2. A portion of a sample screen from Case It Investigator showingcustomizable menu of web sites.


from previous pageCase It!


ReferencesBergland, M.S. and K.K. Klyczek. 1998. DNA electrophoresis module for Case It! Version 2.05. Jungck, J.R. andVaughan, V.R. (Eds.), BioQUEST Library IV. San Diego, CA: Academic Press.

Bergland, M.S., K.K. Klyczek, M A. Lundeberg, K.L. Mogen, and D.L. Johnson. 1999. Case It! - case-study learningintegrating molecular biology computer simulations and Internet conferencing. Proceedings of the 20th Workshop/Conference of the Association for Biology Laboratory Education (ABLE), University of Nebraska-Lincoln. S. Karcher,Editor.

Bergland, M.S., K.K. Klyczek, M.A. Lundeberg, D.L. Johnson, and K.L. Mogen. 2001. DNA electrophoresis module forCase It! v4.0 and Case It! Investigator v1.2. In Jungck, J. and Vaughan, V. (Eds.), BioQUEST Library VI. San Diego,CA: Academic Press.

Bergland, M.S. 2004. Case It! home page, http://www.uwrf.edu/caseit/caseit.html.

Klyczek, K.K., and M.S. Bergland. 1996. Case It! Collaborative development of a potential BioQUEST module.BioQUEST Notes 6(2):11.

Lundeberg, M.A., M.S. Bergland, and K.K. Klyczek. 2002. Using pre-service science teachers as research assistants foran international web-based project involving collaborative case-based learning in biology. Conference proceedings,“Pathways to Change: an International Conference on Transforming Math and Science Education in the K16 con-tinuum,” Arlington, VA.

Lundeberg, M.A., K.L. Mogen, M.S. Bergland, K.K. Klyczek and D.L. Johnson. 2002. Fostering ethical awarenessabout human genetics through multimedia-based cases. Journal of College Science Teaching, 23:64.

Lundeberg, M.A., M.S. Bergland, K.K. Klyczek, D.L. Hoffman. 2003. Using action research to develop preserviceteachers’ beliefs, knowledge and confidence about technology. Journal of Interactive Online Learning, 1 (4), http://www.ncolr.org/jiol/archives/2003/spring/5/index.html.

from previous pageCase It!

Job AnnouncementBiology Computing Facility, Hamilton College

The Biology Department at Hamilton College, Clinton, NY seeks a motivated individual to operate and maintain a newNSF-funded computing facility as part of a bioinformatics initiative. This is a two-year grant-funded, administrativeposition. The facility will house a computer laboratory/classroom and a GCG (Wisconsin package) based bioinformaticsserver located in the New Science Center to open June 2004. Duties include maintaining Mac workstations, administrationof a server-based application, and development of accessible technology interfaces for faculty and students. Experience orinterest in OSX, UNIX based server administration, and HTML programming is desired. Some flexibility in schedulingpossible, salary based on previous experience. Applicants should forward a resume and names and contact information ofthree references by April 17, 2004 to:

Stephen Festin, Ph.D.Director, Biology Computing Facility

Hamilton College198 College Hill Road

Clinton, New York [email protected]

Hamilton College is an Affirmative Action, Equal Opportunity employer and encouragesdiversity in all areas of the campus community.


His notions of synergism were picked up as a primarymetaphor by “Bucky” Buckminster Fuller in the post-World War II love affair with technology and later in thefield of “synergetics.” BioQUEST workshop leader PeterTaylor’s historical analysis of H. T. and Eugene Odum’s“systems ecology” arose as well in that context of techno-logical optimism (Taylor 1988). In the work of MargaretMead, Gregory Bateson, and Norbert Wiener, a focus inthe 1950s and 60s was the transfer of engineering notionssuch as cybernetics, positive feedback, and autoregulationto systems thinking in anthropology, political science, andbiology. In the 1970s, James Miller’s book, LivingSystems, serves as a period piece to represent the embrac-ing of these concepts. Furthermore, the journal Currents inModern Biology changed its name to BioSystems, which ithas remained ever since, and later the Journal of Biologi-cal Systems was established complete with explicitreferences to systems theory in its charge to manuscriptwriters. While many would feel that these references aretwo outmoded perspectives, I would argue that all of thebooks on complexity as well as those on Small Worlds(including Linked and Nexus) express systems rhetoric andperspectives explicitly. Thus, it would seem that biologists,mathematicians, and computer scientists have had “sys-tems thinkers” in their midst for a long time and continueto sustain a conversation with reductionistic colleagues.

In order to continue this dialogue, we will ask participantsto not only consider this history, but we will ask them toexplicitly use software such as Physiome to understandphysiological systems, GIS to understand ecosystemanalysis, and Environmental Decision Making, by H. T.and E. C. Odum, to explore systems ecology. In this way,we hope to engender conversation about what a contempo-rary “systems biology” curriculum will look like andwhether the promises to consider integration acrossbiological scales--molecules, networks, cell, organs,tissues, organisms, populations, and ecosystem--will behonored. We hope that you will consider joining us in thisdialogue either by your participation or by writing to us atthe interactive submission site for the workshop.

ReferencesBarabasi, A. L. 2002. Linked: The new science ofnetworks. New York, New York: Perseus Publishing.

Bassingthwaighte, J. 2000. Computational and BiologicalChallenges for the Biomedical Engineer. The WhittakerFoundation. http://summit.whitaker.org/white/comp2.html.

Buchanan, M. 2002. Nexus: Small worlds and thegroundbreaking science of networks. New York, NewYork: W.W. Norton and Company.

Buchanan M. 2003. Small World: Uncovering Nature’sHidden networks. London, United Kingdom: OrionPublishing Group.

Check, E. 2003. Harvard heralds fresh take on systemsbiology. Nature 425: 439.

Ideker, T., T. Galitski, and L. Hood. 2001. A new approachto decoding life: systems biology. Annu. Rev. GenomicsHum. Genet. 2: 343-372.

Howard Hughes Medical Institute. 2003. 50 Years ofCreativity, Risk-Taking, Persistence, Discovery, Commu-nity and Leadership. Annual Report 2003.

Lewin, R. 2000. Complexity: Life at the Edge of Chaos.Chicago, IL: University of Chicago Press.

Miller, J.G. 1978. Living Systems. New York: McGraw-Hill.

Shenk, D. 1997. Data Smog: Surviving the informationGlut. San Francisco, CA: Harper Publishers.

Taylor, P.J. 1988. Technocratic Optimism, H.T. Odum,and the Partial Transformation of Ecological Metaphorafter World War II. Journal of the History of Biology21(2): 213-244.

Tech Talk. 2003. MIT News Office at the MassachusettsInstitute of Technology, Cambridge, Mass.

von Bertalanffy, L. 1928. Kritische Theorie derFormbildung. Berlin. (Modern Theories of Development,An Introduction to Theoretical Biology, Oxford 1933, NewYork 1962).

von Bertalanffy, L. 1932, 1940. Theoretische Biologie. 2vol., Berlin.

Waldrop, M.M. 1992. Complexity: The emerging scienceat the edge of order and chaos. New York, New York:Simon & Schuster.

Watts, D.J. 1999. Small Worlds: The Dynamics ofNetworks Between Order and Randomness. Princeton,NJ: Princeton University Press.

from page 9Systems Biology


Imagine what your teaching lab might look like if it moreclosely reflected scientific practice. Student researchers wouldbe working on focused problems that fit into a broader researchagenda. The generation and interpretation of data would drivethe activity. Supporting information on methods and the resultsof related research would be collected on a need-to-know basis.Students would communicate their results out to a broadercommunity that would critically evaluate and potentially usethem to inform their own work.

The science education community has long lauded the benefitsof this type of authentic inquiry in the classroom. Repeatedlywe have learned that when students ask their own questionsand construct and follow their own line of inquiry, they canbuild profound understandings that transcend textbook knowl-edge. However, setting up opportunities for authentic studentinvestigation is challenging. With too little direction, studentinvestigation can be frustrating, unfocused, and unproductive.For teachers, authentic inquiry teaching methods can demand ashift in teaching style and content focus. It is critical toidentify research domains that are both sufficiently robust andsufficiently defined. Kathy Greene, a professor of education atBeloit College, asserts that it is critical that we find ways to“provide problems that are circumscribed, yet not prescribed.”(BioQUEST, 2003). So how can BioQUEST better supportsuccessful inquiry-driven, “3Ps” approach to learning andteaching that it has so long espoused?

For several years, BioQUEST has been exploring the potentialof problem spaces to address some of the pedagogical opportu-nities and challenges involved with inquiry education. (Seeexamples on page 15.) We are finding that the developmentand use of problem spaces may have significant implicationsfor supporting successful, inquiry-based education as well asfacilitating long-term professional development aroundteaching as a scholarly activity and the integration of researchand teaching.

A problem space is a way of organizing diverse kinds ofinformation and resources that relate to a rich area of investiga-tion. The area of investigation is by nature complex, interdisci-plinary and refers to a specific problem in the “real world” thatneeds to be better understood. The problem space provides

students with background information, rich data sets, quantita-tive research tools, and collaborative communities that willcreate a palette from which informed, authentic researchquestions may be developed and pursued.

Reflecting the nature of the investigative area that theseproblem sets represent, problem spaces should be dynamic.Users are expected to share the information they acquire, theinvestigations they pursue, and the resources they identify. Inan area of established scientific research, new investigationsfollow trajectories sketched by past research. Similarly, theproblem space will grow and expand through contributionsand active participation.

In BioQUEST, the problem space concept was initiallyconceived as a tool for bringing bioinformatics into theundergraduate curriculum through the BEDROCK Project.The publicly accessible molecular databases and freely sharedanalysis tools that have enabled collaboration among bioinfor-matics researchers provided an opportunity for educators.With that opportunity came a danger—that students could usecomputational power and technological capabilities to performsequence analyses with very little conceptual understanding ofwhat, exactly, they were doing. The data sets and analyticaltools had to be provided in the context of biological principles.With the three components together, the problem space wasborn. BEDROCK hopes that these problem spaces will allowstudents and teachers to interpret contemporary molecular dataand explore underlying questions.

Problem spaces, as developed in the BEDROCK project thusfar, have the following elements:• A brief introduction to an area of research, data set or

applied biological problem;• Samples of “open research questions” that might be

addressed;• Examples of handouts, assignments, and other curricular

materials used by other faculty;• Extensive electronic data;• References and links to background materials;• Examples of student work and other projects that explore

the problem space.

BEDROCK problem spaces are in a phase of rapid development at this time. We are activelyencouraging submission of curricular resources that expand upon the topics currently pre-sented or point to entirely new problem spaces. We will gladly work with you to format yourcontent for the web site. Contact us at [email protected] for more information.

Problem Spaces: Finding Ways

to Support Inquiry



The problem space approach leads us to some deeper consid-erations about the meaningful learning outcomes of thestudents engaged in classroom research. That is, instead offocusing exclusively on solutions to problems, we areproposing attention to heuristics and the broader context ofthe disciplinary practice of scientific research. So the studentoutcomes may involve recognizing and working with thetypes of problems, the types of analyses, and the types ofarguments that make up biological research rather than theparticulars of any single question, analysis or argument.

A problem space need not rely solely on mining data avail-able on the web. Given the right circumstances, students canhave the opportunity to collect their own field data. Localsources of information—biological, social, demographic, andspatial—can be part of the investigation. Researchers can askmore questions, look at more results and collaborate withother researchers. More electronic data sets are madeavailable, sparking a new line of inquiry. In these ways,problem spaces are able to circumscribe an area of studywhile still giving it, and us, space to grow.

The problem space concept certainly has utility beyond thebioinformatics arena. Bioinformatics data might naturally fanout towards other areas of biological investigation. Geo-graphic, mapping, weather, census, population, sociological,historical, economic—all kinds of data sets figure intobiocomplex questions being asked in the problem space.And, of course, the initial seed for the problem space is notconstrained by discipline—it can start anywhere.

Each of the examples that follow began with a focus onbioinformatics. However, the significant differences betweenthem emphasize how problem sets can grow in very differentdirections based on types of data available and included andthe researchers’ interests and expertise. For example while allthree problem spaces include sequence data, the HIV/AIDSincludes both sequence and immunological data from a studyof 15 HIV infected patients and the Trp cage problem spacecontains 3-D structural visualizations and models. TheChimpanzee problem space has potential to support questionsof a broader environmental nature by using spatial, climate,demographic, and economic data. We do not have a fixedview of a problem space or how it might develop and thusthese diverse examples are held together not by their domainor structure but by their orientation toward supporting the useof a more open model for teaching and learning.

ReferencesBioQUEST Curriculum Consortium. 2003. Introduction toProblem Spaces. http://www.bioquest.org/bedrock/problem_spaces/

The HIV Problem SpaceTony Weisstein

The Trp Cage Problem SpaceTia Johnson and Rama Viswanathan

Chimpanzee Problem SpaceJohn Greenler and Genevieve Werner

In 1994, several research-ers collected hairs shed inthe night nests of 64 free-ranging chimpanzees, Pantroglodytes, from 20African sites (Morin et al.1994). By genotypingthese individuals, theresearchers were able toglean information aboutthe genetic variation of the

nearly extinct chimpanzee populations. With thesedata, one can ask questions relating genetic variationto issues of geography, climate, and habitat as wellas issues of historical, political, social and economicconditions.

The de novo miniprotein,Trp Cage, provides anopportunity to engagestudents in discussion andresearch on problemsposed in the context ofprotein structure andfunction. A protein’s formdictates its function.

Predicting what these molecules look like from theirgene sequence is an important challenge facingbiologists and chemists. Researching the Trp Cageminiprotein revealed a curious association between itand two other proteins, exendin-4 and GLP-1.

Imagine a virus thatevolved so fast thatnearly every copy wasgenetically distinct; thatthe composition of aninfected patient’s viralpopulation could changedramatically in less than ayear; that the source of a

new infection could be identified on the basis ofgenetic similarity alone. That virus is HIV—and thenew HIV problem space explores questions of themolecular evolution of HIV through sequence andimmunological patient data.




from previous pageProblem Spaces


HistoryThe idea of developing a Trp (tryptophan) Cage Problem Space wasinitiated at the Summer Modeling Institute hosted by the Center forBimolecular Modeling at the Milwaukee School of Engineering. Asattendees of this workshop, we were asked to bring ideas for buildingphysical molecular models, particularly smaller models which would bemore likely to be completed within the three-day event. Dr. RamaViswanathan, Professor of Chemistry and Computer Science at BeloitCollege, had hoped to find a sufficiently small molecule whose foldingproperties could be simulated on a PC using the Molecular Mechanicssoftware for his courses. Tia Johnson had hoped to find a molecule whichcould be used for investigation and discovery in the area of bioinformat-ics and biology education.

BackgroundThe 20-residue miniprotein, Trp Cage, displays spontaneous andcooperative two-state folding in about 4 µs (at room temperature),the fastest folding protein known. The folding of thisminiprotein is hydrophobically driven by the enfolding of a Trpside chain in a sheath of Pro rings. The hydrophobic core isestablished by a close association of a Gly and three Pro residueswith two aromatic side chains — the Trp cage motif. The smallsize, high stability, and fast folding time make Trp Cage an idealchoice for protein folding simulation.

Trp Cage is a glucagon-like peptide (GLP-1) that is synthesized in enteroendocrine cells in the small and large intestinesand is secreted in a nutrient-dependent manner. GLP-1 helps to integrate many of the normal physiological responsesthat occur after eating. Through regulation of processes such as insulin secretion, gastric emptying and hypothalamicpituitary function, GLP-1 plays a major role in regulating nutrient assimilation.

The enzyme dipeptidyl-peptidase IV (DPP IV), found in the human body, destroys GLP-1 within a few minutes. Oneform of GLP-1, called exendin-4, is found in the poisonous saliva of the Gila monster lizard and is resistant to thedestructive enzyme. Determining the structural differences between human GLP-1 and exendin-4 could be critical tobetter understanding and identifying GLP-1 analogs that might be clinically useful for the treatment of human disease.

Areas of Curricular Exploration with TRP CageThe following is a short list of some issues and questions to explore in this rich problem space.• GLP-1 receptor site and control of diabetes;• Exendin-4 (Gila Monster Lizard Saliva) and GLP-1 as drugs for diabetes;

• Model binding to the GLP-1 receptor using a “homologous” receptor crystal structure;• Compare binding of Exendin-4, GLP-1, and a “truncated” Exendin-4 (Trp Cage).• Using such a small sequence to test for robustness and sensitivity of bioinformatics search algorithms such as FASTA and BLAST.

ReferencesVoith, M. 2003. Make Your Own 3-D Models. Chemical and Engineering News 81(49):36-38.

The Trp Cage Problem SpaceTia Johnson and Rama Viswanathan

Physical andcomputergeneratedmodels ofthetyrptophancageminiprotein

Visit the Trp Cage Problem Space at:http://bioquest.org/bedrock/problem_spaces/trpcage/


Chimpanzees as a Model

Endangered Species

Genetic diversity

Between subspecies

Between populations

Why conserve?

Scientific Study

Evolutionary understanding

Land use

Economic value - ecosystem

services

Bush meat

Pets Zoos and circuses

Isolation

Tourism

Geographic

Social behavior

Sequence analysis

Sequence acquisition

Mapping

Parks verses conservation

areas

Politics

NationsNGOs

International (UN, etc.)

Modeling and simulation

Biota

Ecobeaker

EDM

Bio Workbench

Chimp Genome Project

BioQUEST - BEDROCK

Mapping

UNEP - IMS

UNEP - IMS

Static Web maps

Static Web maps

Morphological diversity

Biologicaldiversity

Primatology

Compared with related

species

MigrationPopulation

sizes

Sociology Workbench

Surveys of public

understanding

Spatial Data Workbench

Spatial Data Workbench

Modeling and simulation

Evolutionary understanding

Excel

Chimpanzee Problem SpaceJohn Greenler and Genevieve Werner

BackgroundIn the Chimpanzee Conservation Problem Space we examine aspecific conservation issue using a very diverse and interdisci-plinary collection of tools. Ranging from the molecular togeographic and sociological to economic, the analysis tools,data sets and resources in this problem space cover multiplescales and approaches. The problem space approach to examin-ing issues in conservation may help serve as a model for studentinvestigation in this significantly interdisciplinary field.

In the ChimpanzeeProblem Space, usersexplore the multifacetedand interconnectedcauses of populationdecline of this endan-gered species, andthrough that analysis canbegin to sketch out pathstowards its conservation.The study of chimpan-zees is important forseveral reasons. Froman evolutionary perspec-tive, chimpanzees areone of our closestrelatives as we shareabout 98% of ourgenetic sequence withthem. They are also oneof the few species, otherthan ourselves, thatdemonstrate the ability

to use tools and adapt this behavior to specific environ-mental surroundings. Chimpanzees are also a charis-matic species. As such, they draw significant attentionfrom the general public. This attention has translatedinto more research funding for their study. Chimpanzeeconservation and research can serve as a model forbroader conservation efforts.

Current ContentAt the core of this problem space is the nuclear genetic sequence data from 64 individual chimpanzees collected from 20sites across Sub-Saharan and Western Africa (Morin et al. 1994). These data, collected from several isolated breedinggroups, are characterized by individual animal and location, thus allowing one to ask bioinformatic questions that relateto small- and large-scale spatial variation. The spatial data that students are able to bring into the analysis can includefactors ranging from ecological, geological, and weather to demographic, economic, and political. They can examinedata from the present, past or focus on change over time. They can look at single factors or the interplay of severalfactors.

Internet Mapping Service web site fromthe UN Environmental Program suppliesGIS type data worldwide. http://www.grid..unep.ch/activities/earlywarning/preview/ims/

The beginning of a concept map for the chimpanzeeproblem space.

Student genetic sequencedata, bioinformaticanalysis and phylogenetictrees based on data fromMorin, et al.


Visit the Chimpanzee Problem Space at:http://www.bioquest.org/bedrock/problem_spaces/chimp/


HIV/AIDS Problem SpaceTony Weisstein

HistoryThe HIV problem space originated as a group project at the 1999 BioQUEST SummerWorkshop. Our principal goal at the time was to explore the utility of the newBiology Workbench tool for exploring questions of molecular evolution; the sequencedata from my dissertation on within-host evolution of HIV (Markham et al. 1998)provided an excellent starting point. Later, Sam Donovan, Eric Jakobsson, and

others built the project into a more structured course module that permitted users topose and explore their own hypotheses about HIV evolution. This activity proved

popular at BioQUEST faculty workshops, particularly those sponsored by the newBEDROCK bioinformatics project. Last summer, we began collecting and organizing

additional materials as part of a concentrated effort to develop a range of online problemspaces. In mid-October, the website went live, although further development continues.

Current ContentThe problem space includes:• An introduction to HIV and AIDS, including information on the virus’s structure, genome, life cycle, origin, and

transmission. Also included are a description of the course of infection, a discussion of how HIV causes AIDS, and aglossary of key terms;

• Immunological data (CD4 counts) from each of 15 patients, obtained at approximately six-month intervals. Also includedfor most visits are sequence data from multiple copies of the virus;

• Details of the study from which the data were obtained;• Curricular resources describing how other instructors have used the HIV problem space, and student projects from those

courses; and• The original paper on which the HIV problem space is based, as well as an annotated collection of additional published and

online references.

Coming Soon• Data on which patients were receiving AZT, and for

which visits.• CD8 counts for each visit. CD8+ T cells are not the

primary targets of HIV infection, but several studieshave indicated that CD8 counts substantially influencethe selective pressure on the virus.

• Information on specific mutations associated with theSI (syncytium-inducing) phenotype, which is associatedwith more rapid destruction of immune system andworsened patient prognosis.

PedagogyDuring four-day BEDROCK workshops, we often use theHIV problem space as the first hands-on work session. Webegin with a 30 minute introduction to general HIVbackground and to this particular data set. Once partici-pants have spent some time discussing possible questionsthey might explore, we move into the computer lab andintroduce them to the Biology Workbench, a free web-

Data summary tablefrom the HIVproblem space

A phylogenetictree showingwithin-patientevolution of HIV

A model of the HIV virus

Visit the HIV Problem Space at:http://bioquest.org/bedrock/problem_spaces/hiv/



Chimpanzee from page 17

from previous page

based bioinformatics tool based at the San Diego Supercomputer Center. Groups then explore and analyze the data in whateverway they choose. Because many workshop participants have little or no bioinformatics experience, we have found that the self-contained nature and relatively small scale of the HIV problem space make it a comfortable place for them to start.

Faculty at several institutions have adapted the problem space for their specific course needs. Dr. Rebecca Roberts, at UrsinusCollege in Pennsylvania, was kind enough to share with us her experiences using the problem space for her upper-levelstructural biology course last fall. Throughout the semester, students in this course had studied protein structure, function, andinteraction, learned to use bioinformatics databases and tools, and worked with molecular visualization software. During thelast four weeks of lab time, students were introduced to the HIV problem space and worked in small groups to prepare andpresent posters describing their findings. One student, Tom Seegar, described the experience:

My approach to the lab was to start off by reading the paper and reading other papers before I began to look at the data.

From there I looked at the patients and just thought of some simple comparisons that I could try and make between patients.

[...] Then I made some general observations and compared observations within the patient and patient-to-patient

observations. From here I went back and read more papers to see what research has already been done so I could obtain a

better understanding of what I was looking at. Hard research paid off with a plethora of descriptive papers, which allowed

me to draw some hypotheses. The biggest payoff was testing my hypotheses on the actual data and supporting the

hypotheses. It was a great project where I was able to go through the entire scientific method from start to finish on a short

time scale, while applying what I have been studying throughout the entire semester.

More details of this application of the HIV problem space, including examples of student posters, are available on the website.In addition, Rebecca has agreed to share her experiences with other workshop participants at the May 20-23 BEDROCKworkshop at UCSD.

ReferencesMarkham R.B, W.C. Wang, A.E. Weisstein, Z. Wang, A. Munoz, A. Templeton, J. Margolick, D. Vlahov, T. Quinn, H.Farzadegan, X-F. Yu . 1998. Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline. Proc. Natl.Acad. Sci. USA 95: 12568-12573.

HIV/AIDS

In its current version, the Chimpanzee Problem Space includes:• An introduction to chimpanzee conservation including basic information on morphology, habitat and social behavior of the

chimpanzee as well as ongoing chimpanzee conservation efforts;• Sequence data from 64 chimpanzee individuals and their location across Sub-Saharan and Western Africa;• Details of the study from which the sequence data were obtained;• Curricular resources describing how instructors have used the chimpanzee problem space;• Links to on-line web analysis tools including: • Biological/Genetic Diversity Tools includes links to a database of microsatellite markers characterizing various primate species, data and information from the Chimp Genome Project, and links to Biology Workbench, a tool that allows for the search and analysis of protein and nucleic acid sequence databases; • Spatial Geographic Tools includes spatial data, climate data, and GIS information, data and links; • Computational Modelling and Simulation includes links to several related BioQUEST simulations; • Economic Analysis tools such as links to tools for ecosystem valuation; • Sociological Resources such as links to a database on chimpanzee cultural variations across Africa, and Sociology Workbench, a web collection of online computational resources relevant to sociologists;• Annotated bibliographic resources for further investigation.

Because all of these tools and materials are online, it is possible for learners to experience a diversity of perspectives anddimensions on a classic conservation problem space without the need for expensive and complex hardware and softwaresystems. We hope the Chimpanzee Conservation Problem Space will allow users to be participants in both research andcurricular development while engaging in an interdisciplinary exploration in a broad and complex area of study.

ReferencesMorin, P.A., J.J. Moore, R. Chakraborty, L. Jin, J. Goodall and D.S. Woodruff. 1994. Kin selection, social structure, geneflow, and the evolution of chimpanzees. Science 265 (5176), 1193-1201.


Beloit CollegeBioQUEST NotesDepartment of Biology700 College StreetBeloit, WI 53511

To contribute to the newsletter or to subscribe to BioQUESTNotes, please contact Robin Greenler, Editor ([email protected]). For general information about the activitiesof the BioQUEST Curriculum Consortium, contact us at:

Project AssociateBioQUEST Curriculum Consortium

Deborah Sapp Lynch

DirectorBioQUEST Curriculum Consortium

Ethel Stanley

EditorThe BioQUEST Library

John R. Jungck

Managing EditorThe BioQUEST Library

Virginia Vaughan

The BioQUEST Curriculum Consortium

Web AdministratorAmanda Everse

(608) [email protected]://BioQUEST.org

Biology Department

Beloit College

700 College Street

Beloit, WI 53511

Major support for BioQUEST development and activity hasbeen provided by the Howard Hughes Medical Institute, theAnnenberg/CPB Project and The National Science Foundation,with additional support from Apple Computer Inc., The Foun-dation for Microbiology, and The Center for Biology Educa-tion at the University of Wisconsin-Madison. Any opinions,conclusions or recommendations in these materials are thoseof the author(s) and do not necessarily reflect the views of thefunding sources.

BioQUEST Curriculum Consortium

Robin GreenlerBiocomplexity Project

Sam DonovanBEDROCK Project

Marion Field FassMicrobiology Project

Directors of BioQUEST Projects

Margaret WatermanLifeLines OnLine Project

John GreenlerBiocomplexity Project

Project AssociateBEDROCK Project

Sue Risseeuw

Assistant DirectorBEDROCK ProjectTheresa Johnson

Documents

BQ Notes Template...burst the “dot-com” bubble and a competitive search for an alternative to attract funding and attention was on. One attractive alternative, referred to as “Cracking