Signal Transduction Education
Signal Module - Obesity and Regulation of Food Intake - Course Programme

Dr 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: Jan-Pieter Konsman and IJsbrand Kramer

Text reference: Signal Transduction. Gomperts, Kramer, Tatham. Elsevier/AP (2009).

The regulation of food intake is an excellent theme (context) to teach a number of signalling pathways. The subject is timely, given the (presumed) explosion of obese people and given the proven difficulty to find suitable targets to treat overweight. The subject is also interesting from a polemic point of view; do we control our desire to eat (an act of will) or is our desire (or lack of it) controlled by signal transduction mechanisms that we do not control? With respect to signalling mechanisms, we have limited the molecular details of signalling pathways to the mediators and mechanisms involved in the so-called homeostatic regulation. Furthermore, we only discussed signalling at the level of the arcuate nucleus in the hypothalamus. Focussing on this particular area we have treated signalling by insulin, leptin and ghrelin, each acting on different receptors types and each having specific and common pathways. In this webpage you will find:

1. Student pages
2. Biocomputing and antropometric practical
3. Lecture slideshows

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 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 briefly and simply explained 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 expression, protein activity, interaction between molecules or their subcellular location or any combination of the four. These means include; phosphorylation or dephosphorylation, exchange of GDP for GTP, hydrolysis of nucleotides, allosteric interactions, ubiquitylation, sumoylation, methylation, acetylation, glycosylation, ADP-ribosylation and everything else that has not yet been revealed. Although this is an important message it does not help students to build a conceptual knowledge base.

A systems approach

The general pedagogical 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, applying a sort of “systems approach” to education. Here we explore “signalling in the regulation of food intake”. Other suitable contexts are; cell transformation (see this website), inflammation, immunity (innate and adaptive), olfaction, vision, pain perception, motor functions (smooth and striated muscles), insulin and diabetes, haematopoiesis or mechanisms of development.

A constructive approach

Constructive theory has been chosen as the general paradigm for the organisation of the signal transduction course. 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. 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 the chemical composition and physical properties of the plasma membrane and the nature of receptors and adhesion molecules. 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.
   
   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 in order to consolidate their conceptual knowledge base (or refresh their memory).
   
3. Learning benefits from multiple points of view.
   We treat the subject at the molecular, the cellular and the organism level, in which deal with homeostatic and hedonic regulation of food intake. We also approach the subject from a pathological point of view (obesity) and we explore the current treatment of obesity.
4. Learning is facilitated by authentic activity
   The course contains three types of authentic activities:
   
   1. A group-based project in which teams (4 to 6 students) prepare a website about the molecular mechanisms that regulate food intake. The following subjects were treated:
      1. obesity ; pathology, life style, genetics, related diseases (type 2 diabetes)
      2. homeostatic regulation; systems that regulate food intake; communication between digestive tract, adipose tissue and the arcuate nucleus in the hypothalamus
      3. hedonic regulation; the reward mechanisms involved in the regulation of food intake (and how it modulates homeostatic regulation (collaboration with Dr Jan Pieter Konsman, University of Bordeaux-2)
      4. signaling implicated in homeostatic regulation in the arcuate nucleus; signalling mechanisms of ghrelin, leptin and insulin
      5. actual and future treatment of obesity
      Progress of the group-based project occurs through two formal tutorials with course teachers; these lasted roughly 45 minutes. A third and last correction of the work occurred 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.
      
      Click here to access the webpages produced by the students.
   2. A biocomputing practical in which the students have to explore proteins involved in the regulation of food intake. In first instance students explore Swiss-Prot and OMIM in order to learn more about insulin, ghrelin and leptin. In the second task they have to explore the insulin receptor, learn about its domains/regions and their functions, and they have to provide an image, depicting the different domains/regions of the ectodomain (based on pdb coordinates). In the third task, the student explore in detail the kinase domain, again using pdb coordinates. They compare the inactive and active state of the protein tyrosine kinase.
      
      Click here for a detailed description of the Biocomputing tasks.
   3. A short antropometric practical in which the students measure their weight, thickness of skin folds and their waist and hip circumference. The findings are correlated with body mass index tables and with life expectancy graphs (relative risk)
      
      Click here for the antropometric practical document.

The course programme, instructions for the practicals, relevant articles, URLs of websites and annotated databases are provided on the web (Ulysse virtual office).

Program 20 students SVI632 “Signal Transduction”.

Download: Slideshows as PowerPoint.