• Problem-based learning (PBL);
  • service-learning (SL);
  • problem-based service-learning (PBSL);
  • active learning;
  • HIV/AIDS problem;
  • research-based undergraduate classroom


  1. Top of page
  2. Abstract
  5. Single-Problem Approach
  7. Acknowledgements

In departure from the standard approach of using several problems to cover specific topics in a class, I use a single problem to cover the contents of the entire semester-equivalent biochemistry classes. I have developed a problem-based service-learning (PBSL) problem on HIV/AIDS to cover nucleic acid concepts that are typically taught in the second semester of a biochemistry class. Use of research articles on a specific topic allows developing problems such as one discussed here. The implementation of this problem is similar to teaching literature-based courses but is tailored to undergraduate work. Details of designing and setting up this problem, along with the pros and cons of this approach, are discussed here.

We all use primary research articles in our courses to bring special topics into classes and value a research-based experience. However, it is not easy to incorporate these into introductory courses. Problem-based learning (PBL)11 provides one way that undergraduates can be involved in a research-based experience from early on in their education [1, 2]. PBL problems can energize students by making the material relevant; it teaches them to ask questions and learn to research a topic in depth [3, 4]. PBL traditionally involves problems written for a specific set of topics that student work on for a short period of time. Many such problems are now available [511]. I use a unique variation of this method: using a single problem to teach an entire semester of biochemistry. Here I will discuss the problem, its organization and implementation, and advantages of using a single-problem approach.

At Colorado College, we teach one course at a time. Four courses are taught sequentially in one semester. A semester's worth of information is covered in each course in three-and-a-h alf weeks, with class meeting 5 days a week. Each day on this plan is equivalent to 1 week on a semester plan. Students work exclusively on one class during this time. Organization of the time is left up to the instructor. In science classes, students are generally in the classroom from 9 a.m. to noon and in the laboratory in the afternoon. Biochemistry classes are limited to 16 students due to the available laboratory space.


  1. Top of page
  2. Abstract
  5. Single-Problem Approach
  7. Acknowledgements

The Problem—

On the first day, I divide students into groups of three or four students each and briefly introduce them to the PBL method before handing them the following problem:

You are going to work with Southern Colorado AIDS Project (SCAP) and will consult on the biochemistry of HIV-1.

You will provide biochemical information about HIV and AIDS to the clients of SCAP and present a workshop to the Colorado Springs community on Monday, May 13, 2002.

You will also generate brochures or audio-visual material for SCAP.

What biochemical concepts should you know?

Make an extensive list of learning issues.

Generating Learning Issues—

In the first hour of the class, students work with their group to generate the learning issues. To get students to focus on biochemical concepts, I provide them with a few biochemistry textbooks and encourage them to differentiate between various biomedical fields. We make a list of the biochemical topics (learning issues) on the board using a “reporting out” method. Each group puts one topic on the board at a time. This allows all the groups to contribute to the list-building process. A representative list of learning issues is shown in Table I.

Organizing the Concepts—

Once a comprehensive list of learning issues is compiled, the students correlate various topics on the board with those in the textbooks. Table II shows a correlation of biochemical concepts with the learning issues. Most of the topics that are traditionally covered in the second half of the biochemistry textbooks show up on the board, with the exception of DNA repair and gene regulation. Some AIDS topics, such as AIDS drugs, combination therapy, and effect on the immune response, get a cursory mention, if any, in the textbooks; these topics are, therefore, not correlated to the textbook topics. Now the concepts are organized to determine an order in which we will discuss them (see “Instructor's Notes”).

Assignment Signup—

The HIV/AIDS topic is too broad to be thoroughly investigated in one class. This reality is reflected in the learning issues generated by students. In the interest of time, I provide specific topics within these concepts (HIV and general biochemical concepts) for students to research so that the major areas that we would normally cover in a traditional nucleic acids course would get covered. This list of specific topics is easily created ahead of time. A representative assignment sheet is shown in Table III. It has three content columns: chapters from the textbook, biochemical research topics, and HIV/AIDS research topics. This organization allows students to become familiar with the “big picture” concepts from the textbook before learning about research on specific biochemical topics, which then sets the framework within which HIV research can be understood. For example, understanding DNA replication from the textbook allows for a meaningful discussion of research being done on DNA polymerases, DNA ligases, and HIV reverse transcriptase. I adjust the number of topics on the assignment sheet based on the number of students in the class, with approximately two research articles per student. Thus, each group of four students signs up for about eight topics from the list. Students get a syllabus and a copy of the assignment sheet immediately after the sign up is complete. At this point I explain the daily functioning of the class along with the grading procedures to reduce student anxiety to this new approach to the class. All this is done in the morning of the first day of the class and takes about 3 h.

Library Work—

In the afternoon of the first day, students are ready to go to the library to find the research articles. Students have to work with their groups to submit one article per topic. A group can only submit these articles after they discuss the title, abstract, and figures in each article to determine if the article is on the topic and is sufficiently biochemical. I ultimately decide if the selected articles are appropriate (see “Instructor's Notes”) for the class. This library work and group discussion are an essential part of this PBL experience, as identification of the resources is a key step in finding the information necessary for any problem-solving process. Also, this allows students to retain ownership of the material for the duration of the course.

The selected research articles are tagged with two numbers: the first indicates the presentation order and the second indicates the group responsible for it. The articles are copied, following copyright laws, and are organized in a binder. The binder is divided into two sections: “Biochemical Research Articles” and “AIDS Articles” (Table IV). This organization is essential to avoid confusion on a daily basis. The class is now ready for reading and discussions of these articles.

Class Discussions—

The entire class is held in a student-led discussion format. Everyone reads the material before coming to the class. Discussions of the chapter material are focused mainly on the key concepts. Most of the class time is devoted to discussions of research articles. The introduction of the article relates the general concepts covered in the textbook to the current problems. Discussion of the experimental design, data, analysis, and various experimental techniques introduces students to the research process. By the end of the course, students become very good at discussing research articles as a class.


The last 2 days of the class are entirely devoted to individual presentations where each student presents one research topic independently. The topics generated in the original discussions of learning issues that were not assigned to the groups, such as protease inhibitors, nucleotide drugs, etc., are picked for individual presentations. Once students are more familiar with the material (last third of the course), they select their presentation topics. Presentations are of 20-min duration, and students are encouraged to use PowerPoint. The entire class does not have to read the presentation articles, but all the students have to summarize the key points of each talk. These summaries are graded.

Service Learning—

The approach of incorporating community into learning is called “service learning” [12, 13]. It adds a real-life component to the problem and enriches the class overall; use of it along with PBL is called the “problem-based service learning” (PBSL) method. I have used this problem with and without the service learning component. Although the student evaluations have consistently rated this component to be important, it is not crucial to the implementation of the problem. The nature and scope of service learning can be modified to fit any class size; however, it is easier to incorporate it into smaller classes. In this class, students work with the counselors and clients of SCAP for one afternoon a week and prepare a 2-h presentation (with SCAP) for the Colorado Springs community. Students also use their presentation material to create informational brochures for SCAP. Details of setting up service learning in biochemistry classes are being prepared for a separate manuscript.

Linking Concepts to Prior Coursework—

To learn nucleic acid chemistry requires that student learn about the proteins involved in nucleic acid biochemistry. The HIV genome is RNA-based but it contains several structural proteins, regulatory proteins, and enzymes; this course includes learning about the structure and function of these proteins, along with the host proteins needed for HIV replication. Hence, the course easily links to the protein biochemistry content of the first semester biochemistry course. Thermodynamic, kinetic, mechanistic, and regulatory aspects of nucleic acid biochemistry, especially HIV biochemistry, build on the concepts taught in previous courses, starting from general chemistry. Without the knowledge of these concepts, reading literature articles for this course is not possible. Hence, this course bridges the content learned from the textbooks in previous courses with HIV biochemistry. Based on my experience in teaching biochemistry courses on both the semester plan and our intensive plan, I find that students' ability to retain concepts and build links between courses is primarily dependent on their level of interest, preparation, and innate abilities rather than the plan of teaching.


  1. Top of page
  2. Abstract
  5. Single-Problem Approach
  7. Acknowledgements

Generating Learning Issues—

Students generally start the discussion of the problem with the AIDS crisis in the world. As expected, each group of students generates a slightly different list of learning issues, but there are certain common themes. Most students do not know that HIV is a virus that causes AIDS or that it has multiple strains. Thus, HIV-1, which is part of the wording of the problem, is one of the first learning issues discussed. It quickly leads into a discussion of available drugs and compromised immune response. The students at this stage need to be reminded to make a list of all the biochemical topics that may be involved in the viral cycle, starting from the infection stage. It is crucial to pay attention to the group discussions and ask appropriate questions to keep students from going in directions inappropriate for the class. The key here is to focus the discussion on the biochemical aspects of the disease.

Organizing the Concepts—

Learning issues generated have to be discussed to determine which ones are pertinent to biochemistry. A logical sequencing of concept is also essential. Most biochemistry textbooks discuss DNA storage followed by replication, transcription, translation, and regulation. The infection cycle of the virus follows a similar order and can be used to guide the students. A representative sequence is shown in Table III. It is best to start with the “information storage” section of the book, which allows the class to become familiar with the HIV genome early on in the class. Also, immunology should be discussed early in the course.

Library Work—

Students have to find the research articles on the topics before they have seen them in class. Hence a good set of instructions is needed to aid students to find appropriate research articles. Students are directed to use the assigned topics as keywords and are encouraged to look for articles in specific journals, such as Biochemistry, Proceeding of National Academy of Sciences, Science, and Journal of Biological Chemistry (Table IV).

Student groups are advised to divide up assigned topics among themselves to start research individually. They are asked to read the title and abstracts of a few articles to determine if their search is yielding articles on the assigned topic. They have to select two articles per topic to discuss with their group members. The group has to collectively determine if the content of each article is sufficiently biochemical based on the title, abstract, and figures and has to submit one of the two articles (per topic) to me. Students are encouraged to solicit my help through out this process. Ultimately, I have to decide if the articles selected are appropriate for the class. Students report that literature work is an empowering experience, as they learn valuable skills on the first day of class. Group work at this stage of article selection has improved quality of articles submitted. All of the library work can be done in about 4 h.

Class Discussions—

Students lead discussions on the topics assigned to them. It is important to assign the topics to groups (and not to individual students) to have effective discussions. It minimizes stress, makes workload more manageable, generates better discussion, and it also allows students to learn from their peers.

The groups generally divide up the material equally among group members. They read their sections thoroughly and prepare questions for discussion. In discussing the chapters, only the key biochemical concepts are discussed, such as mechanisms, structures, regulation, and bioenergetics. Students are responsible for understanding the entire chapter and encouraged to clarify any concepts that are not discussed in the class. For article discussions, the group leading the discussion is encouraged to clarify difficult concepts prior to the class. I encourage them to meet with me and to seek additional resources. Discussion of one article can take up to 2 h in the early stages of the class.

Individual Presentation—

The topics for individual presentation are picked carefully to complete the viral infection cycle and to cover topics that could not be normally covered, such as HIV drugs. These presentations come toward the end of the class when the students have learned to discuss the articles. They allow me to test individual student's abilities to research and present a specific topic.

Service Learning—

Students collaborate with SCAP to give a presentation about HIV/AIDS to the Colorado Springs community. They also make brochures for SCAP on various aspects of the disease. Details of service learning aspect of the problem will be discussed in a separate manuscript.

Single-Problem Approach

  1. Top of page
  2. Abstract
  5. Single-Problem Approach
  7. Acknowledgements

To my knowledge, my approach of using a single problem for the entire class is unique, although my trials and tribulations in using PBL are not. I have used the single-problem approach for both first and second semester biochemistry courses. It took me 6 months of reading research articles on HIV topics to build a sufficient knowledge base before teaching this class. In order for this class to be successful, specific topics that students' research and the order in which they are discussed is important. For example, the first time I taught the class I learned that immunology needed to be discussed very early on along with the organization of the (HIV) genome. I need to carefully examine the articles submitted by the students to determine that they are appropriate. It is also important that students work as a part of the group on the assigned discussions.

This problem can be modified to be used in small classes or large, as only so many research articles can be discussed in a semester. The organization of the class may need modification for larger classes, with no more than four groups participating in discussions, so that each student group has significant responsibilities for focused work.

More generally, teachers interested in using a single problem for entire course should consider some of the pros and cons of this approach. I will list some of these as I see them:


  • A single continuous theme connects diverse topics in a survey style class.

  • The students become familiar with the problem early in the course, which allows for an in-depth analysis of the problem.

  • Subsequent discussion of research articles allows them to become familiar with multiple aspects of the same problem.

  • It is easier to build on the prior knowledge as the course progresses.

  • Students develop a sense of confidence in their knowledge of the material.

  • The research aspect of the problem is more focused and much of it is done early in the course, which reduces the student anxiety.

  • Discussions over the duration of the course improve drastically.

  • Students become familiar with the class pattern quickly and are less likely to be distracted by the newness of the approach.

  • Students enroll in the class with the knowledge of the topic and approach, and hence are less resistant to PBL.

  • A single problem being more general is easy to conceptualize.


  • A single-problem approach is difficult for faculty beginning to use PBL in their classes, as this requires learning about a large area of research prior to teaching the class.

  • If the problem does not work as expected, it affects the entire class.

  • Smaller problems can be interspersed more readily into traditional classes without too much anxiety on the part of the instructor.

  • It is easier to familiarize students with PBL using smaller, more focused problems.

  • Writing problems that encompass all the topics that are normally covered in a class is not easy.

  • Smaller problems are easier to write based on knowledge of a special topic or by designing them based on the research articles that one would normally assign to students.

  • Student interest on one specific topic could be limited.

  • It is easier to include a wide variety of topics, and hence cater to larger number of students, using multiple problems.

On balance, I would recommend that faculty choose the style of teaching based on their personality. For those less averse to risk, jumping into a single-problem approach should come naturally.

Overall, this class is an intense course in AIDS biochemistry, which requires students to learn the basic nucleic acid concepts. Students learn to read biochemical literature and learn to work effectively in a group. This class uses the PBL approach to incorporate an in-depth study of a real-life research area that interests students. The problem is not presented in a traditional multi-page format but can easily be converted into it. It is a natural extension of research ideas that many of us already use and provides a relatively easy transition into PBL without the “coverage anxiety” of a new approach [11].


  1. Top of page
  2. Abstract
  5. Single-Problem Approach
  7. Acknowledgements

I have taught this class four times. Evaluations of this course were designed by me to compare the understanding of the concepts in this class as compared with a lecture-based course. For this, initially I wrote the exams in the same format as I would for a lecture-based class. Students had no trouble with the concepts. Students were asked about learning in a group format and about discussions of research articles. Students respond that they learn well under this format but would also like me to lecture on the concepts in the textbooks. They like the thematic nature of the class. They find the course challenging, and yet do not want it to change. They comment on the large time commitment required for this class but think it is appropriate for an upper level undergraduate course. Students especially like the research component of the class and have continued to tell me the value of the course in their research efforts outside the class. Overall, biochemistry majors say this course should be required for everyone in the department. Students also comment that presentation to the Colorado Springs community did not require additional preparation, as they already knew the material in greater depth than required for the presentation.

Faculty who have taken these students in their upper level courses (or research laboratory) have commented on their ability to read research articles, taking initiative in doing library work, their level of preparation, and their confidence. These are faculty both at our institution and other institutions (where students do summer research) and are not themselves using nontraditional approaches in teaching.

Students readily recall and link the concepts taught in prior courses to the concepts in this course. As the course is built on a single problem, it is not really modular in nature, as expected for PBL courses taught using multiple problems. Hence, overall success of the course is dependent on students learning to connect various literature topics into a complete story—the biochemistry of the lifecycle of HIV-1. I have found that the thematic nature of the HIV problem makes it easier for the students to achieve this. Examination topics used for presentations require students' show that they build these links between concepts, and most students are successful in achieving this goal.

Successful completion of this course requires that students understand mechanistic, regulatory, thermodynamic, and kinetic aspects along with the structure and function of biological molecules. Students leave with a better grasp of biochemical techniques and experimental design using this approach.

Table Table I. Learning issues generated by the students
What causes AIDS? How is it transmitted?
What is a retrovirus? What is the viral genome?
What are the symptoms of AIDS?
What is HIV? Where does it come from? How is different from other parasites?
How does cell recognition and cell entry happen?
What is reverse transcription and why does it cause mutations?
How are the viral protein made?
Why does it affect the immune system?
What is its infection cycle? How does HIV use other cells to propagate itself?
What are the drugs used for AIDS?
How do these drugs work? What are cocktails? Would chemotherapy work? Why is there no cure?
How do AIDS tests work?
What causes the drugs to become resistant?
Are there vaccines against AIDS?
How does the immune system work?
How does the virus replicate?
How does the virus affect the immune system?
What causes the progression from HIV to AIDS?
Table Table II. Correlation of learning issues with biochemical concepts
Virus productionDNA replication
Virus genomeGenome organization, RNA
Viral proteinsTranscription and translation
Effect on immune systemImmunology
DrugsPurine and pyrimidine biosynthesis, regulation, and utilization
 Protein structure and function
Viral multiplicationTranscription, translation, signaling
AIDS testingImmunoassays, viral proteins
AIDS symptomsOpportunistic infections (topics related to these)
Protease inhibitors 
AZT, nucleotide drugs 
Drug cocktails 
Drug resistance 
Table Table III. Assignment signup sheet. G1, G2, and G3 represents the groups 1, 2, and 3, the groups that have signed up for research and leading discussion on these topics
Chapter assignmentGroupBiochemical research topicsGroupAIDS research topicGroup
  • a

    a Topics are for individual presentations, with student initials in the parentheses.

Chapter: Eukaryotic genes and their expressionG1Histones/chromatinG3HIV-1 genomeNG
Immunology (handouts)G1No special topics assigned CD4 and gp120 interactionsG2
    CD4+ T cell activation CD8+ T cellsG2
    Cytokines (TNF-α and IL-6)G1
    Apoptosis (gp120 dependent)G3
Chapter: replicationG3DNA polymeraseG2Reverse transcriptaseG1
  DNA ligaseG1  
Chapter: Information restructuringG2DNA repair or recombinationG3Integration of genomeG1
Chapter: TranscriptionG3RNA polymeraseG3Viral RNA packagingG2
Chapter: TranslationG2SynthetaseG1Gag-pol expression (frame-shifting)G3
  TranslationalG2Viral envelope protein (env)G3
Chapter: Nucleotide metabolismG1N/A Nucleotide drugsa AZT, ddI (AS, CH, BR, BG, MM) 
Presentationsa Proteasea (TG, NM) Viral assemblya (JS, SQ) 
  Maturationa (NK)   
  Protease Inihibitorsa (VW, BN, MI)   
Table Table IV. List of AIDS articles used in two classes
  • a

    a 1 refers to 2001; 2 refers to 2002 class selections.

Unique progressive mechanisms of HIV reverse transcriptase RNase H (M. Wisniewski et al. (2000) Proc. Natl. Acad. Sci. U.S.A.97, 11978)1
Nucleosomal arrangements of HIV-1 DNA: Maps generated from an integrated genome and an EBV-based episomal model (S. Stanford-Oakley, et al. (1996) J. Mol. Biol.256, 503)2
Reversal of integration and DNA splicing mediated by integrase of human immunodeficiency virus (S. Chow, et al. (1992) Science25, 725)2
Inhibitors of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase (S. Gabbara, et al. (1999) Biochemistry38, 13070)1
Role of the non-specific DNA binding region and α-helices within the core domain of the retroviral integrase in selecting target DNA sites for integration (R. Appa, et al. (2001) J. Biol. Chem.276, 45848)1
Characterization of the noncovalent complex human immunodeficiency virus glycoprotein 120 with its cellular receptor CD4 by matrix-assisted desorption/ionization mass spectrometry (C. Borchers, K. Tomer (1999) Biochemistry38, 11734)1, 2
Activation of CD8+ T lymphocytes through the T cell receptor turns on CD4 gene expression: Implications for HIV pathogenesis (L. Flamand, et al. (1998) Proc. Natl. Acad. Sci. U.S.A.95, 3111)1
Kinetics of cytokine expression during primary human immunodeficiency virus type 1 infection (C. Graziosi, et al. (1996) Proc. Natl. Acad. Sci. U.S.A.93, 4386)1
HIV-1 envelope glycoprotein induce activation of activated protein-1 in CD4+ T cells (N. Chirmule, et al. (1995) J. Biol. Chem.270, 19364)2
Effects of TH1 and TH2 cytokines on CD8+ cell response against immunodeficiency virus: Implication for long-term survival (E. Barker, et al. (1995) Proc. Natl. Acad. Sci. U.S.A.92, 11135)2
V3 induces in human normal cell populations an accelerated macrophage-mediated poliferation-apoptosis phenomenon of effector T-cells when they respond to their cognate antigen (A. Zafiropolous, et al. (2001) Biochem. Biophy. Res. Comm.281, 63)2
Caspase-dependent apoptosis of cells expressing chemokine receptor CXCR4 is induced by cell membrane-associated human immunodeficiency virus type 1 envelope glycoprotein (gp120) (M. Biard-Piechaczyk, et al. (2000) Virology268, 329)1
The major HIV-1 packaging signal is an extended bulged stem loop whose structure is altered on interaction with the gag protein (A. Zeffman, et al. (2000) J. Mol. Biol.297, 877)1
NMR structure of stem-loop SL2 of the HIV-1 ψ RNA packaging signal reveals a novel A-U-A base triple platform (G. Amarasinghe, et al. (2000) J. Mol. Biol.299, 145)2
RNA signals for translational frameshift: Influence of stem size and slippery sequence (A. Honda, et al. (1995) Biochem. Biophys. Res. Comm.213, 575)2
Proteolytic processing of HIV-1 protease precursor, kinetics, and mechanism (J. Louis, et al. (1999) J. Biol. Chem.274, 23437)1
Palmitoylation of the HIV-1 envelope glycoprotein is critical for viral infectivity (I. Rousso, et al. (2000) Proc. Natl. Acad. Sci. U.S.A.97, 13523)2


  1. Top of page
  2. Abstract
  5. Single-Problem Approach
  7. Acknowledgements

I would like to thank Hal White for teaching me the PBL approach and for his help in writing this manuscript. Rod Boyer gave me early feedback on the content of this article. I would also like to thank Harold Jones and Diane Alters for their editorial help. I also would like to thank the Chemistry department and the Colorado College for fully supporting my experiments with pedagogy.

  • 1

    The abbreviations used are: PBL, problem-based learning; SCAP, Southern Colorado AIDS Project; PBSL, problem-based service learning.


  1. Top of page
  2. Abstract
  5. Single-Problem Approach
  7. Acknowledgements
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