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Overview
Signal Transduction Education  
Signal Module at U-Bordeaux - Cell Transformation - Course Programme    
SIGNAL TRANSDUCTION at the UNIVERSITY OF BORDEAUX
(a course description)

UNIVERSITY OF BORDEAUXDr IJsbrand Kramer
Signal Transduction - Course SVI632 - 6 ECTS
3rd year Cell Biology and Physiology
University of Bordeaux
Avenue des Facultés
33405 Talence, France
Email i.kramer@iecb.u-bordeaux.fr
Website http://www.cellbiol.net

Teachers: Sophie Layé, Sophie North and IJsbrand Kramer

Signal TransductionText reference: Signal Transduction. Gomperts, Kramer, Tatham. Elsevier/AP (2002).

 

Introduction

The subject of signal transduction has expanded dramatically over the last ten years and providing a comprehensive view of what is on the market is no longer tenable. Teaching signal transduction in a “catalogue-of-pathways” manner has not done and will not do justice to this complex and beautiful subject. Even concentrating on the “main principles” has become a fruitless effort because, as for passing on messages within the cell, everything goes. In fact, the main principle of signal transduction is explained briefly and simply by stating that: in order to reply to a changing environment, extra cellular cues or altered metabolic conditions, cells apply any possible means leading to the necessary alteration of protein activity, their interaction with other molecules or their subcellular location or any combination of the three. These means include; phosphorylation or dephosphorylation, exchange of GTP, allosteric interactions, ubiquitylation, sumoylation, methylation, acetylation, glycosylation and everything else that has not yet been revealed. Although this is an important message it does help students to build a conceptual knowledge base.

A systems approach

The general pedagogically message thus follows that teachers should try to be restrictive, not exhaustive: restrictive in the sense that teachers should search for a comfortable context that allows the exploration of two or three signal transduction pathways. We have decided to develop the signal transduction course around one particular context, a sort of “systems approach” to education. We have chosen “cell transformation”, but many other contexts are possible; obesity, chronic inflammation, immunity, olfaction, vision, pain perception, motor functions (smooth and striated muscles), insulin and diabetes, haematopoiesis or mechanisms of development and others. We consider it important that the teachers have good affinity for the subject in question, preferably linked to research interests, because certain students like to discover that their teachers are not merely translating textbooks into lectures.

In such an approach only a limited number of pathways are treated and, in the course described here, we relate these pathways to their capacity to regulate the cell division cycle or cell survival. At the end of the course, the students have to be able to explain the process of cell transformation, its consequences for the cell and for the organism (loss of function of organs, general state of inflammation, anorexia etc).

For more information about the teaching of signal transduction we refer to our article in CBE-Life Sciences Education).

Pedagogical paradigm

A constructive approach

Constructive theory has been chosen as the general paradigm for the organisation of the signal transduction. We summarize it as follows (for more information, see slide show).

  1. Learning involves the active construction of a conceptual knowledge base.
    For this reason we have chosen a systems approach, an all embracing context that allows students “a story to tell” (rather than a list to learn).
  2. Learning is reflective and builds on (and consolidates) existing knowledge.
    The first lectures deal with a repetition of the Cell Biology courses of the first year, with particular attention to epithelial tissue, the way cells adhere to each other and to the extracellular matrix. We repeat the chemical composition and physical properties of the plasma membrane and conclude that the majority of first messengers would require a transmembrane receptor in order to transmit their signal into the cells. In these lectures we repeat the subject of receptors, either cell membrane or intracellular, we repeat the notion of affinity (on- and off-rates of ligands) and we reiterate that signals, if they were to have a prolonged impact on cell behaviour, will have to enter the nucleus, there to change gene transcription. One afternoon will deal with the cell division cycle and its essential points of control (G1, G2 and metaphase).

    As part of a more global constructive approach, we have developed Cell Biology multimedia resources which accompany the students throughout their teaching path and which make it particular simple to provide them with exact references (ressource X, item Y) in order to consolidate their conceptual knowledge base (or refresh their memory). General referrals to earlier biochemistry (for protein-protein interactions), cell biology and physiology courses are made throughout the course. In addition, the students are informed that the course exam will contain a few multiple choice questions about “elementary matters” such as the composition of ATP, GTP, RNA and DNA, the composition of the plasma membrane, cytoskeletal components, transcriptional regulation and DNA replication. Because these multiple choice questions featured in the first year, the students know exactly what to expect.
  3. Learning benefits from multiple points of view.
    We place cell transformation in different perspectives. We treat it as an error of signal transduction; by showing how constitutive active kinases, GTPases and loss of function of tumour suppressors deregulate cell function. We place it in the perspective of loss-of-physiological function, destruction of tissue and the adoption of aberrant functions. We also show that tumours create an inflammatory environment and that this may cause systemic effects such as loss of appetite and change of social behaviour. This latter aspect, in turn, allows introducing the JAK/STAT pathway in the context of behaviour and regulation of food uptake. Finally we treat the subject in the context of chemotherapy and of novel approaches in cancer therapy (Gleevec, Herceptin and others).
  4. Learning is facilitated by authentic activity
    The course contains two types of authentic activities:
    1. A biocomputing practical in which the students have to explore protein domains, at the level of sequence and structure. With these domains they build a short signalling cascade from the EGFR to Ras. Because their experience is still limited, the description of activities is rather detailed. In the practical students explore PDB, Expasy/SwissProt and EntrezGene and use RasMol or PyMol to visualize structure. Students repeat the detailed protocol for analysis of the SH2 and SH3 domain (Grb2/Sos), the Ras-Sos interface and for demonstrating conformational changes between Ras bound to GDP or GTP. The students then implement their acquired skills for the molecules relevant to their project (see below): for instance c-Abl/Gleevec, ERBB2/Herceptin, EGFR/Iressa or others. Biocomputing has been treated briefly in the first year Cell Biology course, as part of two short active learning projects (more information), where students are asked to explore proteins involved in adhesion (example b-catenin) and their genes using Expasy/Swiss Prot and EntrezGene. General BioComputing is taught in a special course in the first term of the 3rd year (before the signal transduction course).

      See here for a description of the Biocomputing practical.
    2. A group-based project in which they prepare a website on the subject of targeting signal transduction pathways in the treatment of cancer (for more instructions go to Project 2007 or Project 2006. The instructions for the project are provided during the first introductory lecture. The students form groups around the different subjects (3-5 members each). For the project “Herceptin and breast cancer” (2007) the choice of subjects was:
      1. pathology of breast cancer
      2. molecular genetics of breast cancer
      3. ERBB receptors and their signal transduction pathways
      4. Inhibitors of the EGFR (ERBB1) and ERBB2 pathway
      5. Treatment of breast cancer
      The students are given URLs of websites and annotated databases, book chapters and other documentation to start reading about the subject. They prepare texts + images on TWIKI, a collaborative document management system. The reason for this collaborative platform is simply to expose students to new opportunities that provide novel ICT. Such platform is not really necessary for on-campus education and the students tend not to exploit it to the full. They prefer to communicate orally and reserve internet-based communication for out-of-study activities.

      Progress of the group-based project occurs through two formal tutorials with course teachers lasting roughly 45 minutes per group. A third and last correction of the work occurs in the last week of the course, when the students have finished the web-document and receive comments on text and images from the course teachers. Access to the TWIKI management system is blocked two weeks before the exam so that they focus on revision. Marks and comments are provided one week after the exam, together with the written exam mark.

      After the production has been marked, a last verification occurs before putting the documents on the Cell Biology Promotion Website. This can be rather labour intensive because the website should not contain serious errors or ambiguities (given the sensitivity of the subject).
Pedagogical contract on the virtual office

All information relevant to the course, including some important review articles, is placed on the Web-based Learning Support System “Ulysse” (a virtual office, developed by the teaching support service of the University of Bordeaux (Prof Jacques Queyrut)). Students have to sign in to get access to their “pedagogical contract”. Results are also communicated via this support system.

Aims
  • Understanding, on the basis of a number of examples, how external cues, through the intermediate of a receptor and their downstream signal pathways, modify cellular function.
  • Learning to communicate acquired skills and knowledge with society by means of novel information and communication technology
  • Developing skills for organising group-based activities
Objectives
  • be able to provide a detailed transcription of cell transformation and its consequences for the cell and for the organism.
  • be able to describe how protein domains are involved in the formation of signalling cascades.
  • be able to visualize protein structures with RasMol of PyMol and to highlight important characteristics of adaptor and effector proteins.
  • be able to describe the sequence of events, from membrane to nucleus, that constitute the Ras/MAPK, PI 3-K/PKB and JAK/STAT pathway.
  • be able to describe how these pathways affect the cell cycle, protein synthesis and cell survival.
  • be able to produce a multimedia document dealing with all the above on the TWIKI collaborative plateform.
Course programme (example year 2007)

The course of 6 ECTS has roughly 55 hours contact time divided over 12 weeks (semester). Within the third year curriculum, Thursdays are reserved for “Signal Transduction”.

Download: Slideshows as PowerPoint.

23 students BCP608 » Signalisation Cellulaire «

Date heure Evénement lieu
01 february 10h-12h Introduction of biocomputing practical
Reference: Signal Tranduction pocket edition
(ST) pp393-410
Espace alpha
Bat A22
14h15-17h lecture 1A: » introduction of the system: cell transformation« and “introduction of the group-based projet” Kramer download PPT
(reference; ST pp225-232 and pp246-255)
lecture 1B » revision ; the plasma membrane, epithelial cells and their junctions, extracellular matrix, gene transcription” Kramer download PPT
(reference ; ressource BioCell »la cellule et sa membrane «, » les molecules d’adhérence «. ST Ch 14, pp314-334).
IECB
Salle Haut-Brion
08 february 08h-12h Work on course project Bât B6
RdC
14h15-18h Lecture 2A : premier messagers, receptors, protein kinases and phosphatases”, Kramer download PPT
(reference; ST pp
Lecture 2B : » GTPases, kinases, phosphatases«, Kramer download PPT
(reference: ST Ch 4, pp71-95, Ch 11, pp257-281 and Ch 17, pp373-392)
IECB
Salle Haut-Brion
15 february 08h-12h Work on course project  
14h15-17h Lecture 3 : » Growth factor receptors : from Ras to MAPkinases” Kramer download PPT
(reference; ST Ch 11 pp256-282)
IECB
Salle Haut-Brion
08 march 08h30-12h Biocomputing practical
(référence : ST Ch 18, pp393-410)
Espace alpha
Bat A22
14h15-17h Lecture 4: » cell division cycle and the role of Rb and TP53 North
(référence, ST pp232-246)
IECB
Salle Haut-Brion
15 march 08h30-12h Biocomputing practical:
(référence : ST Ch 18, pp 393-410)
Espace Alpha
Bat A22
14h15-17h Lecture 5 » PI 3-kinase and PKB« Kramer download PPT
(reference : ST Ch 13, pp299-313)
IECB
Salle Haut-Brion
22 march 09h-12h Biocomputing practical:
Search for PDB files for project, search OMIM
Espace Alpha
Bat A22
14h15-
17h
Lecture 6: »anticancer therapy«, Kramer download PPT
(see document in Ulysse)
IECB
Salle Haut-Brion
29 march 08h-12h Work on course project IECB Salle Yquem
14h15-18h 45 min progress report per group (by appointment) IECB
Salle Haut-Brion
05 april 09h-12h Work on course project/ workshop on Photoshop (by appointment) Bat5 computer cluster room
14h15-18h Lecture 7 : »JAK, STAT and cachexia « Laye
(référence : ST Ch 12, pp283-297)
IECB
Salle Haut-Brion
19 april 08h-12h Work on course project Bat5 computer cluster room
14h15-18h 45 min progress report per group (by appointment) IECB Salle Haut-Brion
26 april 08h-12h Work on course project Bat5 comp cluster room
14h15-18h Work on course project/staff available for questions IECB Salle Haut-Brion
03 may   Dead-line of course project is 07 May, last suggestions/corrections by course teachers  
  Work on course project B5 computer cluster room
10 may 14h14-17h Slide show presentation of course project, questionnaire and evalutation of course
END
IECB Salle Yquem
    For results of student projects, consult: Active Learning Projects  
Evaluation

The students are marked for

  • their multimedia document - Weighting factor 0.4
  • their biocomputing practical - Weighting factor 0.2
  • written exam of 1h30 min - Weighting factor 0,4
    • multiple choice questions about molecular composition of cellular components (cell biology course)
    • multiple choice questions about signal transduction
    • assay question about one of the three pathways treated in the course

Students have to mark each others’ contribution to the project according to the following coefficients:
Good contribution: 1,0
Weak contribution: 0,6
Little or no contribution: 0,3

The individual mark is obtained by “group mark x coefficient”. If students contest their coefficient they are asked to prepare an oral exam on any of the subjects treated in the course project and that is not part of the written exam (subject determined by course organizer). The mark for the performance in the viva voce will replace the project mark.

Concluding remarks

Strong points

  • The students are satisfied with the module (see course questionnaire below).
  • Some greatly enjoy the production of a multimedia document.
  • Some find it challenging and rewarding that their achievements are exposed on the Web.
  • Authentic activities make the course very lively and improves contact between teaching staff and students
  • The retention rate is a near 100%

Weak points

  • Introducing pathology into the course is risky and one member of the teaching staff should have some medical training in order to avoid serious errors and to be able to coach the students that work on this aspect of disease.
  • Students that have chosen the pathology or the treatment of cancer will benefit less from the lectures, and generally require more coaching, than those that have chosen the more molecular subjects.
  • The contribution/intervention of staff may turn excessive when students are unable to prepare a good multimedia document. One cannot expose badly written documents or unjust information to people in search for information to better understand their disease and its treatment (unethical). A possible outcome to this is that badly written documents are not exposed but serve as a “template” for students of the next year. This approach would provide an extra collaborative dimension.
  • Students have little graphical experience and tend not to develop original artwork. Introducing a workshop on the making of illustrations would be beneficial but this is extremely time-consuming. It would require at least two full days of teaching and practising.
A clash of culture

Experience has learned that a relative large number of students at the University of Bordeaux (compared to UCL, London) satisfy with an average mark (5/10) because, by and large, passing the “degree” is their objective. Paradoxically, the consequence of this is that the better you prepare the learning activities and their supports, i.e. the more you wish to contribute to their “success” and comprehension of the subject, the more students pull out as a 5/10 suffices. The organization of the curriculum at Bordeaux, modules in parallel, the extremely diversity of subjects and the lack of choice, forces students to economize their efforts; the harder you work on signal transduction, the less time you will spend on biochemistry. This state of affairs leaves teachers short of parameters to measure the quality/effectiveness of their teaching skills (evidence-based teaching). Finally, a majority of students appear not appreciate the notion that excellence or academic success may contribute to future employment. Such “anglo-saxon” approach to education is judged heretic. Unfortunately this attitude is not going to bridge the growing gap between what universities offer and what society requires.
Finally, exposing students’ achievements on the web has a sense of “exhibitionism” but we have decided that perhaps through public exposure of the work of teachers and learners, French society may regain an interest in putting Universities on a more constructive political agenda.

Course questionnaire (students reply in bold)

Name of Module: BCP608, signalling

Year: 2007

Name of teachers: Kramer, Laye, North

1) Content of each session too much correct too little
1 2 3 4 5
1   13 3  
2) Content of the sessions too easy correct too difficult
1 2 3 4 5
    8 9  
3) Quality of illustrations bad OK very good
1 2 3 4 5
    2 7 8
4) Clarity of sessions bad OK very good
1 2 3 4 5
    5 10 2
5) Did you learn something? little   a lot
1 2 3 4 5
    2 6 8
6) Where the different subject cohéren not at all   very good
1 2 3 4 5
    3 6 8
7) Does the course respond to your expectation: perfectly   not at all
1 2 3 4 5
5 4 5 3  
8) the course project is a: bad idea   very good idea
1 2 3 4 5
  1 4 4 8

9) how would you mark this module (x/10)

     
8.7/10        

Comments

Do you have suggestions with respect to adding or removing aspects of this cours;

  • more coaching with the construction of the web-site web
  • staff should describe more clearly their expectations of the web document
  • slide shows should not be in English
  • course project demands too much time

 

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Last Updated July 2, 2009 9:37 PM | admin news