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Articles. Teaching the Extracellular Matrix and Introducing Online Databases. Within a Multidisciplinary Course with i-cell-MATRIX. A STUDENT-CENTERED ...... els, 2nd ed., Berrett-Koehler, San Francisco, CA. [26] D. Stead (2005) A review of ...
Q 2010 by The International Union of Biochemistry and Molecular Biology

BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION Vol. 38, No. 2, pp. 79–84, 2010

Articles Teaching the Extracellular Matrix and Introducing Online Databases Within a Multidisciplinary Course with i-cell-MATRIX A STUDENT-CENTERED APPROACH Received for publication, June 2, 2009, and in revised form, July 22, 2009 Joa˜o Carlos Sousa, Manuel Joa˜o Costa, and Joana Almeida Palha‡ From the Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal

The biochemistry and molecular biology of the extracellular matrix (ECM) is difficult to convey to students in a classroom setting in ways that capture their interest. The understanding of the matrix’s roles in physiological and pathological conditions study will presumably be hampered by insufficient knowledge of its molecular structure. Internet-available resources can bridge the division between the molecular details and ECM’s biological properties and associated processes. This article presents an approach to teach the ECM developed for first year medical undergraduates who, working in teams: (i) Explore a specific molecular component of the matrix, (ii) identify a disease in which the component is implicated, (iii) investigate how the component’s structure/function contributes to ECM’ supramolecular organization in physiological and in pathological conditions, and (iv) share their findings with colleagues. The approach—designated i-cell-MATRIX—is focused on the contribution of individual components to the overall organization and biological functions of the ECM. i-cell-MATRIX is student centered and uses 5 hours of class time. Summary of results and take home message: A ‘‘1-minute paper’’ has been used to gather student feedback on the impact of i-cell-MATRIX. Qualitative analysis of student feedback gathered in three consecutive years revealed that students appreciate the approach’s reliance on selfdirected learning, the interactivity embedded and the demand for deeper insights on the ECM. Learning how to use internet biomedical resources is another positive outcome. Ninety percent of students recommend the activity for subsequent years. i-cell-MATRIX is adaptable by other medical schools which may be looking for an approach that achieves higher student engagement with the ECM. Keywords: Extracellular matrix, OMIM, bioinformatics, student-centered learning.

The extracellular matrix (ECM) provides cellular support to tissues and organs and contributes to various physiological processes like filtration, cell migration, and cell adhesion. A clear understanding of many biological processes such as the decrease in skin elasticity and compressibility in aging or scar formation or pathological conditions—for example, tumor invasions, joint diseases, and atherosclerosis—requires understanding of the molecules in the matrix and their supramolecular organization [1, 2]. The biochemistry and molecular biology of the ECM is, thus, a key subject that should be contemplated in undergraduate medical and biological sciences curricula. It is most fortunate that undergraduate medical curricula provide opportunities to introduce students to human ECM under various disciplinary perspectives. Histology may cover the basal lamina of epithelia and the typical

appearance of collagen fibers in bone tissue. Developmental biology and embryology may approach the relevance of adhesion to cell migration during development. Microbiology can relate a microorganism ability to invade tissues to the structure of the ECM. Pathology may relate the metastatic potential of a tumor to secretion of matrix metalloproteinases. Finally, biochemistry may focus on the chemical and macromolecular composition of the bone. When the facets of ECM are imparted to students in different courses, more attention is necessary to ensure an appropriate overall content and chronological coherence. Disciplinary fragmentation might impact negatively on student cognitive engagement. Such impacts can be overcome by increased curricular integration or, when this is not possible, by the development of projects or blocks which pull together different disciplines around a common subject [3–6]. In medical education, integrated curricula have been extensively adopted as a means to counteract caveats of disciplinary curricula such as the lack of clinical application and lesser student motivation [3, 4, 7]. Multidisciplinary curricula are aligned with cognitive theories of learn-

‡ To whom correspondence should be addressed. Tel.: 351253-604817; Fax: 351-253-604809. E-mail: [email protected]. This paper is available on line at http://www.bambed.org

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DOI 10.1002/bmb.20338

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BAMBED, Vol. 38, No. 2, pp. 79–84, 2010 TABLE I Instructional objectives for i-cell-MATRIX Instructional objectives 1) Identify the components of the ECM 2) Define the biological functions of the ECM 3) Find diseases associated with components of the ECM 4) Relate the structure/function of ECM components with physiological and pathological processes 5) Use the internet resources OMIM and PubMed to find answers to your questions 6) Organize and present the findings orally

thology. The approach highlights the relevance of the individual components in contexts of health and disease and focuses students on the underlying processes and mechanisms. In addition, i-cell-MATRIX promotes a selfpaced discovery of internet resources and, thus, serves as a primer for learning about publicly available databases. This article describes i-cell-MATRIX in detail after 5 years of experience and presents the analysis of feedback gathered from the three most recent editions. METHODS

Intended Outcomes and Instructional Objectives

ing and hold higher potential for promoting the application of knowledge in relevant contexts [8–10]. Reforms in curricula toward higher levels of disciplinary integration have also been advocated in reports on medical education—for example, in the United Kingdom General Medical Council’s ‘‘Tomorrow’s doctors’’ [11]—and also in molecular life sciences education [12]. Integration can be implemented at different levels, depending on the specific idiosyncrasies of courses and of institutions [5]. Even though it may be looked on differently by the various actors in the learning process [13], the literature suggests that curricular integration favors the retention of knowledge [14]. The benefits of integrating courses may be enhanced by the adoption of interactive teaching approaches [15– 17] like Process-Oriented Guided Inquiry Learning (POGIL). POGIL relies on the use of small, self-managed student groups to promote both the mastering of a subject and the development of relevant skills. POGIL adequately promotes student learning of complex topics and is applicable in large classes [18].The approach employs in class activities which are carefully programmed to lead students through stepwise self-directed subject explorations. In POGIL, the instructor facilitates learning interfering as little as possible [19]. Approaches under the framework of POGIL accommodate computerassisted learning easily. The training of students in the use of online resources on molecular life sciences is a responsibility of biochemistry and molecular biology education [12, 20]. It is very important that students appreciate the fantastic potential offered by the interconnectivity of online resources to learn about the organization and linkage of apparently nonrelated molecular pieces of the biological puzzle. Amongst the numerous examples on the incorporation of bioinformatics tools available online in courses of molecular life sciences [21, 22], some testify the existence of a symbiosis of combining the exploration of online resources with the learning of course materials [23]. This article presents ‘‘i-cell-MATRIX,’’ a student-centered approach to the ECM designed for medical students. i-cell-MATRIX was designed as a response to a recurrent lack of interest and difficulties with ECM of medical students, who systematically failed to grasp the biomedical relevance of the subject. i-cell-MATRIX aims at bolstering medical students’ motivation to understand how the molecular components of ECM—elastin, laminin, fibrilin, fibronectin, proteoglycans, glucosaminoglycans, and collagen—contribute to human physiology and pa-

i-cell-MATRIX was introduced with the intention of driving students to: 1) Realize the biomedical importance of the ECM and develop increased interest in the ECM; 2) develop the selfdirected learning habits, through a guided but self-paced discovery; and 3) develop awareness, confidence, and skills in use of internet resources on biological and health sciences. The instructional objectives (Table I), which were delivered electronically to the students, emphasize focus on general principles about the ECM and emphasize the importance of using the internet.

Design and Integration in the Curriculum i-cell-MATRIX has been presented to classes of first year medical students as a compulsory activity in the biochemistry component of a 8-week block on the muscle-skeletal system, which is team taught by faculty of anatomy, biochemistry, histology, and physiology. The course is offered to first year students of a 6-year degree at a public university in Portugal. Students enter the University directly, after 12 years of high-school education. With i-cell-MATRIX students are expected to learn how to make use of the internet to find a disease that is related to a particular ECM component or vice versa and to develop their understanding on the importance of the structure/function of ECM in biological and in pathological conditions. The activity comprises 5 hours, distributed in four sessions which are summarized in the flowchart presented in Fig. 1. Students are assigned to previously randomized groups of five to nine students and, depending on the session, the instructor works either with the whole class or with subclasses of 30–50 students. Table II indicates the developments within each session.

Session 1 (1 hour): Explaining i-cell-MATRIX, Launching the Challenge The first moments are devoted to refocusing the students on general aspects of the ECM and to recapture past knowledge.

FIG. 1. A flowchart for i-cell-Matrix

81 TABLE II The i-cell-MATRIX sessions Session

What happens?

Time (hr)

1

The instructor launches the challenge and presents OMIM and PubMed Students explore online resources and the literature to develop understanding and to prepare oral presentations Oral presentations and discussions in subclasses General class discussion and broad summary contemplating the matrix components addressed by all subclasses

1

2

3 4

1.5

ulty members attend the session and contribute to the discussion. For each class of 75 minute, up to eight groups present their work. The instructor provides feedback on how clear the question under analysis was presented and on how evident the relation between the ECM component and the question in analyses was made. The presentations are not marked for summative purposes.

Session 4 (1 hour): Sum Up 1.5 1

This is done by staging a general class discussion around introductory ‘‘common sense’’ statements, such as ‘‘State and explain whether organs and organisms are composed of freely floating cells’’; or ‘‘State and explain whether cells freely move from one place to another within an organism.’’ The answers to these questions lead to broad conclusions, for example, that the ECM is necessary for cell support and adhesion within tissues, and that cellular tissue invasion requires alterations in the ECM structure. Then, a molecular component of the ECM is assigned to every group: collagen type I, collagen nontype I, dystroglican, elastin, fibrillin, fibronectin, fibulin, glycosaminoglycans (e.g., hyaluronic acid, heparin), laminin, proteoglycans, matrix metalloproteinases, and matrix metalloproteinase inhibitors. Then, groups are challenged to find a disease and one physiological or pathological process in which the ECM component is specifically implicated. Reminders stress the importance of using internet resources and students are directed to Online Mendelian Inheritance in Man [24] and to PubMed. At the conclusion of Session 1, students are required to deliver a brief email to the instructor naming one genetic disease and identifying a function associated with their ECM component—maximum of two sentences. The email message is a straightforward means for the instructor to monitor the groups’ progresses.

Session 2 (1.5 hours): Addressing the Challenge The second session consists of small group discussions and of further exploration of the diseases identified in Session 1. There are two deliverables of Session 2 which should reach the instructor within the following 24–48 hours: (i) A 5–7 minute Power-point1 presentation that should illustrate how the structure and function of the particular component are related and how the component is implicated in features of the disease identified in the previous session; (ii) a report highlighting the relation structure/function/disease. The format of the report has evolved from a summary with limited number of words and a schematic representation of the structure/function relationship adequate to synthesize the group findings, to a written summary of up to 300 words of the same findings. Reception of the presentations before Session 3 allows the preliminary evaluation of students’ achievements. Most students finish the presentations at the end of this session. Nevertheless, additional 24–72 hours are given for the assignment. Experience shows that some groups benefit from the extra time to refine their presentations.

Session 3 (1.5 hours): Oral Presentation In this session, the groups present their work in their subclasses and engage in a general discussion staged with the instructor and the rest of their classmates. Usually, additional fac-

This wrap-up session brings together the various subclasses to revisit the instructional objectives and outcomes. This session reviews the complete set of ECM components addressed by the groups and is particularly important because it is not logistically possible to address all ECM components in the presentations of the subclasses. It is also an opportunity to crossfindings related to pathologies: Students realize that a given ECM component can be involved in multiple physiological processes and implicated in various diseases.

Student Evaluation of the Activity Locating i-cell-MATRIX within an action research framework, we documented the process and evaluated the approach as it unfolded. Adaptations have been introduced as a consequence of observations from previous editions. Systematic evaluations have been restricted to the level 1 of Kirkpatrick’s framework for evaluation of educational activities: How learners perceived the instruction [25]. The impact of i-cell-MATRIX was analyzed from answers to a ‘‘1-minute paper’’ [26] that included the following four items: 1) Please refer to the positive aspects of this activity; 2) Please refer to the negative aspects of this activity; 3) Was this activity useful? (Yes or No). From the second edition onward, an additional question was introduced: 4) Do you think this approach to learning the ECM should be used in the future with first year students? Student evaluations were collected in three consecutive years (n ¼ 310). In the most recent edition, it was administered at the end of Session 3 whereas in the first two editions it was administered at the conclusion of the activity (please recall this at the discussion). The answers to the openended questions were analyzed qualitatively as follows. One author read every answer and identified recurrent mentions to positive and negative aspects in the activity. The most frequently mentioned aspects that emerged from the data collected were sorted into specific categories. The total numbers of ‘‘1-minute papers’’ analyzed were 256, 198 of which from the editions that required answers to the four questions. RESULTS

Student’s Findings The first issue addressed was the ability of students to find the required information. Indeed, students were able to trace various diseases to molecular defects of ECM individual components. Table III lists the diseases students have identified and the implicated ECM component in the five editions of i-cell-MATRIX. Findings proliferated in every edition, beyond faculty expectations.

Student’s Feedback Table IV presents the analysis of students’ answers to the two selected response items of the survey. It is clear that most students, in all cohorts, appreciated the usefulness of the activity as a way of approaching the ECM. In the last 2 years, we have also asked whether this activity

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BAMBED, Vol. 38, No. 2, pp. 79–84, 2010 TABLE III Diseases related to the extracellular matrix reported by students ECM component

Disease

Collagens various types

Alport syndrome, Ehler–Danlos syndrome various types, epidermolysis bullosa various types, osteogenesis imperfecta, Stickler syndrome Muscular dystrophy Duchenne type Cutis laxa, supravalvular aortic stenosis, Williams–Beuren syndrome Marfan syndrome Ehler–Danlos Syndrome type X, glomerulopathy Age-related macular degeneration, cutis laxa Aging, arthrosis, corneal macular dystrophy, heparin-induced thrombocytopenia, Morquio syndrome A, mucopolysaccharidosis various types, osteoarthritis, pulmonary artery thromboemboli, Wagner syndrome Epidermolysis bullosa junctional, Herlitz type Cancer, cirrhosis, chronic pulmonary obstruction, multiple sclerosis, rheumatoid arthritis, Wegener’s granulomatosis Sorsby’s fundus dystrophy, rheumatoid arthritis

Dystrophin Elastin Fibrillin Fibronectin Fibulin Glycosaminoglycans and proteoglycans (chondroitin sulfate heparin, hyaluronic acid, keratan sulfate) Laminin Matrix metalloproteinases Tissue inhibitors of matrix metalloproteinases

should be applied to students when addressing the ECM, which was supported by about 90% of the students. Answers to the open-ended items in the 1-minute paper were read and carefully categorized. The frequency of the categories in students’ answers is presented in Table V. Overall, the written comments were very positive. Significantly, nearly half of the students referred to how the approach had induced them to study the ECM in different ways. The other positive aspects mentioned were motivational, how the activity promoted team work and developed skills and, last but not the least, brought relevance to the subject. The negative aspects had to do with the narrowing of group work to cover only one component and to difficulties in keeping up with the study of other components. The duration of the activity seemed adequately tuned: Only a handful of students considered that more work could be done in Session 1 than finding the matrix related pathology. Also of notice is the fact that in the most recent cohort, when the evaluation was done before the final session, the students still did not have the perception that some of the ECM components had not been covered in their class, which may explain that no comment was made on that, as observed in the other two cohorts, when the 1-minute paper was given at the end of Session 4.

Instructor’s Observations It was interesting to observe that, even though one computer was available for each student, students

generally perform internet searches in groups of three. The time allocated for the sessions was sufficient to accomplish the proposed aims. Even in Session 2, every group succeeded in sending a Power-point1 presentation and report on time. As to the overall activity, faculty’s impressions from classroom observations are that students responded to the challenge with evident enthusiasm. It was clear that exploring the implication of the matrix in human pathologies was a highly motivating trigger. Students demonstrated no difficulties in using the recommended internetavailable resources—OMIM and PubMed. One aspect for which clarifications were sometimes required regarded how deep the diseases should be addressed in the presentation and in the report. In fact, students tended to explore the diseases far beyond what was expected, trying for example to unveil completely the disease etiology, the course or treatment. However, students were encouraged to find aspects of the disease that may call the audience’s interest during their presentations. The instructor realized that the team strategies adopted by the various groups were identical, mostly dividing tasks among the team members and reconvening subsequently for discussions. To promote individual responsibility and lower the odds for group hitchhikers, no information was provided in advance regarding which student would deliver the presentation in Session 3. The received presentation files revealed that the vast majority of groups had indeed met the expected outcomes for i-cell-MATRIX. Presentations tended to emphasize the clinical features of the diseases, including

TABLE IV Answers to the selected response items in the 1-minute paper about i-cell-MATRIX Cohort 2006–2007 (N ¼ 58)

Item About this approach to the ECM, please state if you agree that it was useful Do you recommend this activity for first year students in future editions of the course? NA, not available.

Yes No No answer Yes No No answer

49 (84%) 8 (14%) 1 (2%) NA NA NA

Cohort 2007–2008 (N ¼ 75) 66 6 3 65 8 2

(88%) (8%) (4%) (87%) (11%) (3%)

Cohort 2008–2009 (N ¼ 123) 115 7 1 114 8 1

(93%) (6%) (1%) (93%) (6%) (1%)

All cohorts (N ¼ 256) 230 21 5 179 16 3

(90%) (8%) (2%) (90%) (8%) (2%)

83 TABLE V Analysis of answers to open-ended items of the 1-minute paper on i-cell-MATRIX

Positive aspects Stimulus for learning: Students words are autonomous research/self-learning/the required deep study of the subject/effective learning of the subject Motivational aspects: The activity is described as motivating/appealing/participative /dynamic/fun Higher relevance: Students highlight integration with pathologies/the relevance of the subject Team work: Students mention group work/sharing of knowledge Skills: Quotes include training of schematic and organized study/training of oral presentations Negative aspects Coverage of group work: Focus on a single matrix component/group Studying other components: Superficiality of the presentations/difficulties in understanding how deep to study/poor quality of some presentations Logistical issues: Separate oral presentations of the various classes Time issues: Too long/time management Individual responsibility: Random choice of the student who deliver Session 3 presentation

pictures and/or schemes of the observable consequences of the diseases that added a spontaneous component of authenticity to the study of the molecules. DISCUSSION

The ECM is a complex structure that fulfills important structural and functional roles in animal tissues. Unfortunately, it is difficult to center student’s attention on the matrix molecules in classes of life sciences. This report presents i-cell-MATRIX, a student-centered teaching approach that leverages student interest by exposing associations between the ECM’s molecules and physiological and pathological processes at the organism level. Furthermore, i-cell-MATRIX introduces students to internet-available resources. Students become actively involved in the process of learning and work in teams. This approach fits nicely in Guided Discovery, which is known to be beneficial to student attitudes and achievements in science courses [27, 28]. The learning benefits of anchoring biochemical concepts in contexts, which are relevant to students have been referred in the literature [29]. Analysis of 3 years of student’s feedback shows that it is successful in increasing student motivation and interest on the subject. Exploring the issues underlying pathologies seemed, as far as observations suggest, important to motivate learning. i-cell-MATRIX is triggered by statements that relate to contexts that students find exciting (in our example, the quest for medical students to understand diseases). This is also the case of other approaches that have been implemented in various curricula throughout the world with evident advantages for student motivation and learning, such as problem-based learning [30, 31]. Class activities that foster self-directed subject explorations with students working in small, self-managed groups, similarly to POGIL, are also known to benefit class outcomes [32].

Cohort 2006–2007 (N ¼ 58)

Cohort 2007–2008 (N ¼ 75)

Cohort 2008–2009 (N ¼ 123)

All cohorts (N ¼ 256)

32 (55%)

21 (28%)

64 (52%)

117 (46%)

24 (41%)

13 (17%)

47 (38%)

84 (33%)

6 (10%)

43 (57%)

51 (41%)

100 (39%)

20 (34%) 6 (10%)

8 (11%) 20 (27%)

31 (25%) 18 (15%)

59 (23%) 44 (17%)

27 (47%) 14 (24%)

21 (28%) 2 (3%)

53 (43%) 26 (21%)

101 (39%) 42 (16%)

10 (17%) 4 (7%) 2 (3%)

13 (17%) 2 (3%) 0 (0%)

0 (0%) 13 (11%) 4 (3%)

23 (9%) 19 (7%) 6 (2%)

The combination of the student-centeredness embedded in i-cell-MATRIX and the exploration of OMIM pitched the subject to unexpected levels of medical authenticity. The diseases brought medical students into close contact with examples of molecular pathologies. Students were responsible for gaining knowledge of and explaining the patterns and relationships between the molecules and the organism. In the written feedback, students recognized that, with this activity, a broader understanding on the implications of ECM components in normal physiology or in specific disease conditions was attained. Furthermore, while addressing a pathology associated with an individual ECM component, students often, against their expectations, made their own discoveries of interactions with other matrix component or transmembrane and cytoskeletal proteins. Much of the information brought to class is not found in textbooks. Furthermore, students discovered that mutations in different ECM components may lead to the same pathology, thus revealing how the interplay of several matrix molecules is a prerequisite for the ECM’s function. Students discovered independently broad principles about how the ECM works that imparted fascination to the students. Another interesting aspect that students realized was that, despite the similarities in the matrix’s molecular composition across tissues, there are tissue specificities, such as in the case of glomerular filtration in the kidney, in which laminin is very relevant; or bone strength provided by collagen type I, or blood vessels elasticity as provided by elastin. Had the teacher been responsible for selecting the content to be imparted, the classes would inevitably be poorer and less interesting. i-cell-MATRIX addresses one of the perils underlying self-directed learning activities: The loss of control over student’s progress. In this regard, the deliverables defined and communicated at the start of the course were very important. Nevertheless, students often extended their quest for symptoms, courses of the dis-

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ease and treatments, even though these were not the focus of investigation for this activity. However, it is clear from the student’s feedback and from the instructor’s appreciation that the disease in itself was a triggering motivator for the study of structure/function of each individual ECM component. An interesting positive aspect in respect to the presentation was that several students reported that it contributed to systematization and organization of the collected information to present to the class, which was considered. Some aspects referred negatively by students are difficult to avoid with large classes but easily solved otherwise. For example, the fact that they were not able to attend the complete set of presentations, but only those pertaining to their subclass; and not all ECM components are studied in each subclass. We noticed that in the last edition, when the 1-minute paper was distributed at the end of Session 3, the number of students referring negatively to this aspect decreased. Our observations support the idea that this aspect can be overcome at least to some extent in the wrap-up session. Another aspect referred by some students was the fact that there was no previous announcement on the student selected to deliver the presentation. This strategy is key to promote student individual responsibility, by requiring that all students prepare for the session and we shall insist on it in future editions. The main limitations in our results are that we were unable to measure short-term or long-term learning gains of the students. It should be interesting to evaluate, in later years, when the diseases of the muscleskeletal system are addressed, the retention of knowledge regarding ECM and its individual components. In order to do that, a pre- and post-test approach will be devised and implemented in future editions of the course. In summary, i-cell-MATRIX associates the levels of the organism and of the structure/function of molecules and is appropriate to introduce in the basic sciences curricula. It can be easily incorporated in the medical curricula of other schools, irrespective of the curricular organization of the course. The likely outcomes are higher student motivation and the development of self-directed learning habits and awareness of the importance of using web resources to learn molecular life sciences. i-cell-MATRIX is an exercise that should be considered at the introductory level wherever learning of ECM structure and function is intended.

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