CBE Life Sci Educ 5(1): 19-26 2006
DOI: 10.1187/cbe.05-11-0127
© 2006 American Society for Cell Biology
Meeting Report: Teaching Signal Transduction
IJsbrand Kramer*, and
Geraint Thomas
* European Institute of Chemistry and Biology,
University of Bordeaux, 33405 Talence Cedex, France; and
Department of Physiology, University College
London, London WC1E 6BT, United Kingdom
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ABSTRACT
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In July, 2005, the European Institute of Chemistry and Biology at the
campus of the University of Bordeaux, France, hosted a focused week of
seminars, workshops, and discussions around the theme of "teaching
signal transduction." The purpose of the summer school was to offer both
junior and senior university instructors a chance to reflect on the
development and delivery of their teaching activities in this area. This was
achieved by combining open seminars with restricted access workshops and
discussion events. The results suggest ways in which systems biology,
information and communication technology, Web-based investigations, and high
standard illustrations might be more effectively and efficiently incorporated
into modern cell biology courses.
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INTRODUCTION
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The European Institute of Chemistry and Biology (IECB;
http://www.iecb.u-bordeaux.fr)
at the campus of the University of Bordeaux hosted a very intense week (July
04–09, 2005) of seminars, workshops, and discussions around the theme of
"teaching signal transduction." This text is a report of that
week. The purpose of the summer school was to offer junior lecturers a good
basis for reflection on the development of their teaching program and to offer
experienced, established lecturers/professors an opportunity to rethink their
teaching subjects and methods. Such events are common in the world of research
but rare in the realm of university teaching. The week had a double character:
three days of limited access workshops, providing hands-on experience with
bioinformatics, systems simulation, and cellular and molecular illustrations,
and two days of open access seminars around the themes of "systems
biology" and "information and communication technology (ICT) for
blended learning in university courses." The workshops were attended by
12 participants from various European countries and the open access seminars
attracted 25 teacher-scientists (see Figure
1). For more information please consult:
http://www.cellbiol.net
(section "summer schools"). Not all participants currently run
their own signal transduction course; many taught or were going to teach
signal transduction as part of courses in cell biology, biochemistry, or
pharmacology.
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CONSTRUCTIVE THEORY AS A GUIDELINE FOR THE WEEK
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The general paradigm, acting as a reference for discussions during the
week, was provided by the launch presentation (IJ.K.), about
"constructive theory"
(http://www.cellbiol.net/docs/Constructive_teachingKramer.pdf).
The presentation elaborated four main principles of constructive teaching: 1)
learning involves the active construction of a conceptual knowledge base; 2)
learning is reflective and builds on, and consolidates, existing knowledge; 3)
learning benefits from multiple views of a subject area; and 4) learning is
facilitated by authentic activity, authentic resources, experiences, and
sharing.
The general observation was made that universities apply constructive
teaching to only a limited extent. Curricula often have a progressive
approach, starting with the basics and building from existing knowledge toward
more complex understanding, but there is no built-in mechanism to consolidate
the acquired knowledge. Many basic subjects (basic theories, key ideas, and
even important molecules) do not get a second mention in the curriculum;
teachers do not return to these subjects in any explicit way. For example, it
is a revealing exercise to underline or highlight keywords in textbooks or
lecture handouts on basic subjects ((bio)chemistry, mathematics and physics)
and then screen for second mentions in more advanced modules in the biology or
medicine curriculum (i.e., cross-referencing). Ideally, these keywords should
return every year because recall is a fundamental step in the consolidation of
any knowledge. In practice, a lack of repetition means that much of the
knowledge acquired in the basic courses is no longer operational in later
stages of the curriculum. All too frequently teaching staff blames such lack
of retention on a lack of interest or intelligence among students, or some
blame it on their colleagues. The following point was raised: "How would
teaching or research staff score if they sat for first-year exams in
chemistry, physics, and mathematics?" It was anticipated that such an
experiment would not provide evidence for the common belief that "you
first need the bricks in order to build the house." In other words,
little of the so-called "basic knowledge" routinely forced into
undergraduates across Europe is actually used day-to-day by scientific
professionals.
At a much more subtle level, evidence was provided that even classic cell
biology textbooks fail in some ways to apply the principle of consolidation of
knowledge or the inclusion of multiple views. Many subjects are treated in an
almost anecdotal way, reflecting the way cutting-edge research advances. For
example, ribosomes are shown synthesizing nonexistent proteins; the signal or
destination peptides of specific proteins are shown, yet these proteins are
never revisited in a meaningful context; transport through the ER and Golgi is
described using irrelevant viral proteins; glycosylation is explained as the
decoration of an object (a nondescript particle) rather than a specific,
biologically relevant (glyco)protein. These weaknesses are then propagated
unquestioningly in the classroom. With respect to gene expression, we work on
general principles but without mentioning genes coding for proteins visited
earlier or yet to be seen. Trying to "work through" the different
aspects of cell biology using a smaller number of functionally important
proteins would help students to create an integrated view of increasingly
complex cellular events.
With respect to the teaching of signal transduction, the same principles
apply; whenever possible one should make reference to past and to parallel
modules. For example, when teachers explore the binding of ligands to
receptors, they should make reference to the lectures that treated molecular
bonds (electrostatic, hydrogen, or van der Waals). Ideally speaking, those
chemists who teach bonding theories should work around real examples, e.g.,
adrenaline binding to its receptor. As another example, one may refer to
pharmacology lectures and repeat terms like agonists, antagonists, or
Kd. This way one subject reinforces the other and a more
integrated view is obtained. A further example is the Wnt pathway: when the
Wnt pathway is treated, one could take the opportunity to come back to the
cytoskeleton and show that ß-catenin has both a structural role, holding
cadherins and the actin cytoskeleton together, and a signaling role. From a
constructive theory point of view, teachers should, if the subject has been
treated in earlier modules, return to the cell cycle and refer to cyclin D,
cell cycle phases, and replication in order to convincingly explain to
students why the arrival of ß-catenin in the nucleus can drive the cell
cycle. When the Wnt pathway is taught in the context of colon cancer, a review
of the characteristics of intestinal epithelia (first-year histology
lectures?) and of stem cells and cell differentiation would be appropriate.
With respect to insulin signaling, one has a good opportunity to return to
biochemistry and repeat glucose metabolism and glycogen synthesis; one should
also mention the opposite actions of adrenalin and glucagon. A revision of
protein synthesis would not be out of place in order to explain the anabolic
effect of insulin. One can also return to physiology and review the endocrine
function of the pancreas. Finally, it is a good idea to make reference to any
lectures about membrane transporters and revise how glucose traverses the
plasma membrane.
The use of constructive theory in practice means that teachers either come
back to these subjects in the lecture (teaching intracellular junctions,
glucose transporters, etc.) or give reading assignments with precise
indications of which book and which pages to read. In a more active approach,
students can be asked to write a 300-word abstract on, or make a detailed
drawing of, the role of ß-catenin in the assembly of cellular junctions.
Coupling such assignments to integration of knowledge across the curriculum
strengthens students' grasp of key concepts in signal transduction.
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HOW TO TEACH SIGNAL TRANSDUCTION: PROVIDING A CONTEXT WITH MULTIPLE VIEWS AND AVOIDING COMPREHENSIVENESS
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Because of the complexity of signal transduction pathways, putting various
signal transduction pathways in a clear physiological or pathological context
is almost a necessity. Teaching signal transduction in a
"catalogue-of-pathways" manner does not do justice to this complex
and beautiful subject or to biology as a whole. Neither does the
"catalogue" help that fraction (at least 50%) of the students who
need to see the "larger picture" before they can commit signaling
cascades to memory. Many curricula still take the view that the subject should
be covered, almost exhaustively, to ensure that at least it has been
"said once and for all." Such an approach may serve as a means to
discriminate between excellent and poor first-year students but it will not
favor comprehension or an appreciation of how cells deal with extracellular
cues. It will not contribute to a conceptual knowledge base.
There are numerous contexts that could serve as "coat hangers"
from which to hang facts and perspectives while treating various signal
transduction pathways. If the choice is with the teacher, it is recommended to
choose a context that is closely related to his or her research area, because
students like to discover that their teachers are not merely translating
textbooks into lectures and that teachers can be scientific role models.
Examples that easily come to mind are "fear, flight, or fight",
insulin and diabetes, cell transformation, cell differentiation (e.g.,
hematopoiesis), muscle contraction (smooth and striated), vision, olfaction,
apoptosis, inflammation and immunity, or mechanisms of development. These
different physiological or pathological contexts should also include practical
aspects. Examples include the treatment of diabetes or its detection, why some
people are color blind, how we treat cancer, how signal transduction knowledge
is applied to the development of new drugs, how we block the clonal expansion
of T-cells in order to prevent rejection of transplanted organs, etc. The
general message that the organizers wished to convey is 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.
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TEACHING SIGNAL TRANSDUCTION IN "FIXED" CURRICULA
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Many teachers felt, however, that the content of their lectures was
determined by the faculty and that there was no alternative to
"cataloguing," principally because of time constraints. This is
particularly true for those teaching in medical courses, where curricula have
very clear benchmarks (things physicians should know and those skills that
should be mastered). Not every teacher or student is unhappy with this state
of affairs. Others feel that the constructive approach is perhaps too
cumbersome; they would have to work day and night in order to manage hundreds
of students and fulfill all of the criteria of constructive teaching (with no
time left for research). Recognizing these constraints, the organizers and
participants nevertheless felt that changes have to occur when lecturers
and/or students show signs of "wear and tear," even when this
would cause a gap in the curriculum content. However, it was felt that the
constructive learning approach might reduce the "learning fatigue"
often experienced by (medical) students that results from studying several
broad disciplines either in rapid succession, or simultaneously, but in very
little depth. Making time for more focused, highly integrated,
cross-referenced exercises in a comfortable teaching context would reduce the
burden on students and, equally important, provide a much more rewarding
teaching experience for teachers. The message to faculty deans or course
tutors is that there is room for such changes. To give an example, we
conducted the following experiment: All students at the European Molecular
Biology Organization (EMBO) Receptor Mechanisms and Signal Transduction course
of 2004, held in Bordeaux, had attended signal transduction lectures during
their education in a variety of disciplines (biochemistry, pharmacology, cell
biology, or in specialized signaling courses). The majority felt that their
university had done a satisfying job, all of them were actively involved in
signal transduction research, and yet only 13% passed a spot test (with a 5/10
pass grade) at the start of the course (details of this test are found in the
Appendix). We feel that this experiment makes the point that the knowledge
teachers have transmitted (and assessed) does not necessarily remain
operational.
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DOES SYSTEMS BIOLOGY PROVIDE A NEW DIMENSION TO UNDERSTANDING AND TEACHING SIGNAL TRANSDUCTION?
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The day of seminars on systems biology illustrated that the progress in
molecular biology, particularly in genome sequencing and high-throughput
measurements, might enable the collection of comprehensive data sets on the
components of cellular systems. However, this "molecular
botanizing" provides little information on system performance. Although
an understanding of genes and proteins continues to be important, systems
biologists focus on understanding a system's structure and dynamics. Hans
Westerhoff gave a very good introduction to the subject of systems biology and
focused on the power of the insights obtained during the development of
metabolic control analysis. He clearly illustrated that there are no
"key" enzymes in pathways; pathway control is distributed among
all of its components. This, he suggested, means that targeting oncogenes in
signal transduction cascades does not necessarily mean that the pathway is
going to be effectively inhibited. One should also consider targeting an
upstream or downstream component (which feeds forward or backward on the
oncogenes). With these insights he set the scene for Reinhart Heinrich, who
demonstrated that kinases play an important role in the amplitudes of signals,
whereas phosphatases control their duration. He demonstrated that kinases act
in a logarithmic mode, whereas phosphatases act in a linear mode. As to the
question "why are signal transduction pathways often composed of three
to four kinases?", Heinrich showed that multikinase pathways conduct the
signal much faster than two-component cascades, with the optimum at four
kinases in a row (on average cells employ three kinases in a cascade). Ursula
Klingmüller showed that the STAT pathway, resulting in the expression of
Sis, could be best described as a circular pathway of phosphorylated STATs
entering and unphosphorylated STAT leaving the nucleus. The IL-6R acts as a
remote sensor that influences the entry/exit rate of STATs and thus Sis
expression. She also showed that there is considerable variation within and
between experiments due to simple technical difficulties that must be
understood and then adjusted for before reliable signaling system modeling can
even start. Denis Noble took what Sidney Brenner had dubbed a "middle
out" approach to understanding the functioning of the heart. The model
is based on experimental data on the behavior of most of the major ionic
currents: the fast sodium, L-type calcium, transient outward, rapid and slow
delayed rectifier, and inward rectifier current. The model also includes basic
calcium dynamics. Using this model he studied the cause of re-entrant
arrhythmias by changing the characteristics of ion channels that conduct the
above-mentioned major ionic currents.
A clear message of all speakers was that systems biology often provides
"counterintuitive" insights and therefore acts as an excellent
supplementary source of inspiration for the design of molecular biology
experiments. New data sets on system performance and on the molecules involved
would, in turn, provide new parameters for improved modeling of signal
transduction systems.
The participants in the summer school considered how this information could
be introduced into signal transduction teaching. The introduction of a simple
model would help students to see the relationships and patterns between the
components of signaling systems, how they feed forward or backward and
influence each other. Some students might find it challenging to try to
understand the systems of differential equations often required to construct
systems biological models. However, new interfaces that hide the intimidating
formal rate laws behind friendly interfaces or mathematical approaches that do
not routinely use difficult rational functions, e.g., the power functions seen
in biochemical systems theory, are becoming more widely available and popular
(see below). The advantage of the inclusion of a model in the teaching is the
same as the inclusion of a physiological context. Models help students to see
the "relatedness" of molecular events. The model could also serve
as a starting point to let students design a wet-lab experiment that might
provide them with data to verify the model. However, there are limits to what
is currently achievable. Virtually all established researchers and teachers of
signal transduction have been raised and have prospered in the
"reductionist school" and so have little appreciation for the
complex behavior that can emerge from even the simplest of biological systems
subject to feedback control.
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ILLUSTRATING A SIGNAL TRANSDUCTION LECTURE COURSE
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We all know that a good illustration is worth a thousand words, but why
should teachers need to know how to make these illustrations? Why should they
not leave it to professional illustrators? The very first reason is because
teachers are keen students of their own subject discipline and they need to
make the illustrations to clarify matters in their own mind. Second, teachers
often have their own points of view and these are not always shared by
existing illustrations. Third, some teachers fear to breach copyright rules if
they use pictures from books or Web sites. Lastly, and importantly, personal
illustrations may serve to illustrate the teaching (and research) skills of
the teacher (teachers as role models).
As one example of the illustration process, Oliver Hantschel, from the
Centre of Molecular Medicine in Vienna, Austria, gave a superb overview, with
excellent molecular animations, of what protein tyrosine kinases look like. In
particular he focused on c-Abl (and its oncogenic variant Bcr-Abl) and its
inhibition by the novel anticancer drug Gleevec (Glivec or Imatinib). His
seminar was a very good example of how molecular structure helps us to
understand and communicate the mechanisms of regulation of protein kinases.
His seminar also illustrated the descriptive power of molecular illustrations
and animations. The summer school participants then spent the rest of the day
creating diverse representations of both c-Abl and any protein of their
choice, using the coordinates obtained from the RCSB Protein Data Bank
(http://www.rcsb.org/pdb/)
and the program PyMOL
(http://pymol.sourceforge.net/).
Graham Johnson, a professional biomedical illustrator
(http://www.fivth.com/)
and now a Ph.D. student at the Scripps Research Institute, La Jolla, CA, gave
a wonderful description of how an artist has turned into a leading biomedical
illustrator who has revolutionized the molecular illustration in cell biology.
He gave brief instructions on the composition of lecture slides, of how to
give direction to the flow of events that one wishes to illustrate, and how to
focus attention on visual aspects of the presented material. The participants
then moved to their laptops and worked hard with Adobe Illustrator and
Photoshop, under Graham's tutelage, to draw their own lipid membranes and
proteins, and, in line with constructive theory, c-Abl.
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ORGANIZING AUTHENTIC ACTIVITIES IN SIGNAL TRANSDUCTION COURSES
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"Authentic activities" are an essential aspect of learning and
teachers should include these in their signal transduction courses (for our
definition of authentic activities, see Table 2 on p. 565 of an article by
Reeves et al., 2002; see Higher Education Research & Development
Society of Australasia,
http://elrond.scam.ecu.edu.au/oliver/2002/Reeves.pdf).
Below, we will highlight three aspects of how authentic activities could
function within signal transduction courses.
Coordinating Activities with a Web-based Learning Support System
Betty Collis, Shell professor at the Faculty of Behavioral Sciences,
University of Twente, The Netherlands, gave an impressive presentation on the
use of ICT in support of blended learning courses
(http://www.cellbiol.net/docs/ICT_for_blended_learning_Collis.pdf).
The term "blended learning" refers to different types of
resources, different types of learning activities, different places and times
where activities take place, and different ways that people interact with each
other. The process is coordinated in an efficient way via a Web-based learning
support system that she, and her team at Twente, has developed (TeleTOP,
http://www.teletop.nl).
The trainees can choose between a predominant Web environment (working at
home) and a predominant classroom environment. Instructive teaching elements
occur in both settings. We highlight two aspects of her presentation here.
She and her colleague Jef Moonen (who contributed to the workshop session
in the afternoon) have published extensively on active learning. The success
of Betty and Jef's courses relied on a meticulous design of complex
activities. Apart from assessment and feedback, the main contribution of the
organizer/instructor to courses consists of discovering where instructions are
ambiguous, where course material is incomplete or insufficient, where
objectives are not clearly defined, or where deadlines are unrealistic. With
respect to course design, Betty suggests the following preparation cycle:
first, design the learning activities and their supports; second, design the
assessment procedure; third, choose the Web environment to support the
approach; and finally prepare your lectures and all the rest.
Using Bioinformatics to Bring a Sense of Insight and Discovery
Geraint Thomas, of the Physiology Department, University College London,
United Kingdom, gave a demonstration of the use of bioinformatics in signal
transduction teaching courses. Over the last six years he has developed a
second-year course in which students explore proteins, at the level of
sequence, structure, and domain composition, in the context of signal
transduction. The students learn to build signaling cascades based on the
interactive properties of proteins. The increasing number of databases, many
now containing extensive annotation and numerous hyperlinks, has provided
staff and students with an overwhelming repository of information. In the
past, a student or teacher had to work extremely hard to track down articles
for sequences, structures, or annotations. The Internet now offers all of this
in a splendid and efficient way; nevertheless, there is far too much
information for a student to explore blindly. Luckily, cell signaling can
provide an excellent starting point and rationale for approaching this vast
resource, because much is known about signaling elements, their structure, and
how it relates to their function, and their roles in health and disease. By
using signal transduction as a gateway subject, students with only modest
molecular and structural biological backgrounds can undertake detailed
molecular explorations in silico.
Geraint made the point that many protein analysis programs do not
necessarily provide a user with accurate biological prediction, e.g., the
number or orientation of transmembrane spans, and that verification at
different levels is necessary to reach increasingly sound conclusions. To make
students explore these databases, teachers have to provide a framework
comprising a set of relevant "entry level" questions and a
"toolbox" portal of URLs to different useful databases and
processing servers. These are easily constructed in a modular form that allows
additions and deletions to be used to tailor teaching materials to any class.
An example is available through
http://www.cellbiol.net/MRindex.htm
(section "active learning projects"). Using this approach, the
participants spent the afternoon collecting and analyzing sequences,
extracting and rendering molecular models, searching for phosphorylation
sites, and predicting potential protein kinases and other
protein–protein interactions. Ideally, as a part of signal transduction
course, students would follow up this introductory material by applying the
same tools and resources to their own individual (or group) studies of key
signaling proteins or cascades.
Geraint reported that this process works particularly well if students are
asked to submit small project reports (individual or group efforts) or make
public presentations. Here the students are only allowed to describe the
results of their de novo investigations into their target molecules. All of
the data should be obtained from the analysis of primary bioinformatics
sources. A class can rapidly build for itself a good annotated database on the
structure-function properties of many components of signaling systems.
Database searches and analysis are authentic activities: they have a high
level of relevance to the professional situation, they are open-ended because
one can always find more, and they provide many opportunities for fruitful
interaction between students. Searches could be complemented by visualization
of proteins and domains using PDB coordinates and appropriate rendering
software. Many curricula still reserve these activities for postgraduate
courses, but experience has shown Geraint that second- or third-year
undergraduates are perfectly able to assimilate this kind of information and
enjoy the challenge. Indeed, student efforts often supersede recently
published authoritative reviews in front-rank journals (shortest time to
"obsolescence" is currently three weeks), uncover putative new
members of signaling protein families, or even find powerful counterexamples
to well-publicized hypotheses or relationships.
Modeling Signal Transduction Pathways
When signal transduction pathways are taught, students will inevitably ask
whether they have to learn it all and why cascades are so long and so
complicated. Standard answers include hand waving and mention of
"amplification" or "signal integration." The answer is
certainly not based on experimental proof. For example, astute students may
ask, "Why do cells respond to minute concentrations of TGFß1
without an apparent production of second messengers or the inclusion of long
amplification cascades?" In contrast, "Why does EGF, acting at
similar concentrations, need so many intermediates before its signal reaches
the nucleus?" "Why is all the attention focused on protein kinases
and not on protein phosphatases, because they too must play an important role
if signaling cascades are regulated by phosphorylation?"
Certain students would like to find answers to these questions by modeling
the pathway they are studying. To do so, they must insert the different
components, second messengers, kinetic equations, and dissociation constants
into a model. Such an activity would give an idea of the scale and amplitude
of a process (e.g., Does the ligand act in the fM or µM range? How many
receptors do cells actually have?) and what the effects are if parameters are
changed (e.g., inclusion of a protein kinase inhibitor or modifying the
activity of a protein phosphatase). This activity also has relevance for
professional settings. For example, pharmaceutical researchers have turned to
modeling in order to better select the targets for therapeutic intervention,
biochemists now require systems insights, and cell biologists need to tackle
the complexity of responses observed in single cells as opposed to
populations.
Two software programs were presented and explored by the summer school
participants during the meeting and these might be suitable for teaching
activities.
- PLAS (Power Law Analysis and Simulation,
http://www.dqb.fc.ul.pt/docentes/aferreira/plas.html),
a program created and demonstrated during the week by Antonio Ferreira of the
Department of Chemistry and Biochemistry at the University of Lisbon,
Portugal. It was designed specifically to aid in the modeling of biological
systems and handles either power law formulations or the more familiar rate
differential equations of undergraduate biochemistry. It is freely available
for download and is particularly attractive for use in an educational
environment because all of the equations can be seen and manipulated.
- PathwayLab, created by InNetics
(http://innetics.com/),
a commercial product not freely available. The program was demonstrated by one
of the participants, Elie Järnmark from the University of Skövde,
Sweden. A useful feature of this program is the side-by-side presentation of
the pathway diagram (e.g., a typical signal transduction cascade scheme) and
the pathway analysis (production of intermediate products of the pathway). The
program has a useful palette of common reaction mechanisms to "drag and
drop" that masks the complexities of their corresponding algebraic
formulations.
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A REMARK ON COURSE ASSESSMENT
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What students learn is greatly determined by what teachers assess and how
they assess it. Assessment, other than multiple-choice questions (MCQ), is
time consuming and fatiguing (in particular when student numbers become
large). European universities have a tendency to assess at the very end of
semesters (two sessions a year), leaving it entirely to students to organize
their study time. Strong students have no problem with this approach but
average students may lose out because they cannot manage their time or
prioritize their activities properly.
In the workshop that followed Betty Collis' seminar, the participants came
back to the subject of assessment because statistical analysis revealed that
certain subjects always scored badly in their respective end-of-term exams,
regardless of the teaching effort that had been put in. Although not all
examples could be drawn from signal transduction courses or materials, what
emerged is that students may avoid certain subjects entirely, because they are
difficult or uninteresting. This practice allows them to focus on subjects
they can master more easily and increases their chance of a good mark. Two
examples: Jamie Weiss reported that the subject of the bacteriophage Lambda's
lytic versus lysogenic pathways, as part of her first-year course on the
Principles of Molecular Biology, always scored badly in the MCQ exam, despite
her efforts to link the molecular subject to important issues such as the
latency phase in HIV infection. Another example was provided by Ediz
Demirpence, who reported that medical students repeatedly failed to memorize
the enzymes involved in the synthesis pathway of steroids. They were unable to
integrate this material to create useful hypotheses describing the likely
physiological outcomes of medically relevant enzyme deficiencies. The use of
"in course" or "just-in-time" assessments was felt to
be one way to stimulate students to tackle the difficult subjects that
teachers find important. It might prove extremely useful to target the main
assessment of the student's ability to handle complicated materials in this
way, rather than wait for final assessments where students are under pressure
to be selective about their coverage.
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SOME REMARKS ON THE EVENT
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The event brought together outstanding speakers, workshop facilitators, and
a small group of teachers eager to work hard, discuss, and discover more about
teaching. The format, a mixed program of seminars, workshops, and
presentations by participants, worked extremely well. A computer cluster room
with good ambience and a multimedia projector with full access to the Internet
was found to be vital. The improvement in working conditions and the
flexibility achieved by having a competent and interested informatics engineer
at hand should also be noted. Lastly, many teachers found it difficult to
raise funds for attending this type of event. Forward-looking universities
should perhaps earmark some resources for this purpose.
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APPENDIX
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The following spot test has been employed at the start and the end of an
EMBO lecture course on "Receptor Mechanisms and Signal
Transduction" organized by Alasdair Gibb, IJsbrand Kramer, and Geraint
Thomas, held at the University of Bordeaux in 2004 (for more information about
the event, consult
http://www.cellbiol.net,
section "Summer Schools").
We developed this test for two reasons:
1) We wanted to immediately assess the heterogeneity of knowledge among the
course participants at the onset of the week. This information was used to
tailor both the design and execution of the immediate course and also to more
accurately plan future events. 2) We wanted to assess whether or not the
lecture course actually delivered a measurable increment in student
knowledge.
Notably, the students were not warned that there would be a spot test at
the start of the week and they were also not told that the test would be
repeated at the end of the course. We believe that this element of surprise
helped us to make a more accurate assessment of the class.
Spot test EMBO 2004
Correct answers in bold.
Receptor Mechanisms
- The simplest possible model for the interaction between a ligand, A, and
its binding site on a receptor, R, is:
k+1 is the
- association equilibrium constant
- affinity constant
- association rate constant
- activation constant
- Is KA =
k–1/k+1 the:
- association equilibrium constant
- affinity constant
- association constant
- dissociation equilibrium constant
- The dissociation equilibrium constant for the interaction between a ligand,
A, and its binding site on a receptor, R,
has dimensions:
- M–1
- M
- s–1
- Ms–1
- The del Castillo-Katz model of receptor activation:
supposes that when an agonist combines with its receptor, an inactive complex,
AR, is formed. The receptor then undergoes a conformational change that
results in an active form of the receptor, AR*. For an agonist with relatively
poor ability to activate the receptor, a very high agonist concentration would
cause the proportion of receptors in the active state to be:
- 1.0
- close to 1.0
- exactly 0.5
- much less than 1.0
- If a receptor has constitutive activity (so the receptor can sometime
isomerise to the active state in the absence of agonist) an inverse
agonist would:
- inhibit the receptor activity
- increase the proportion of receptors in the AR (inactive) state
- decrease the proportion of receptors in the AR* state
- not affect the proportion of receptors in the unliganded (R) state
- An antibody has an equilibrium constant of 1.0 nM. In order to occupy more
than 90% of antibody binding sites, the antibody concentration should be at
least:
- 1.0 nM
- 5.0 nM
- 10.0 nM
- 90.0 nM
Signal Transduction
- GTP binding proteins
- - are activated through phosphorylation on serine residues
- - are characterized by 5 highly conserved GTP binding regions
- - are usually active in a GTP-bound state and inactive in a GDP-bound
state
- - have the capacity to hydrolyze ATP
- Cadherin
- - is involved in tight junctions
- - is involved in desmosomes and adherens junctions
- - is linked to actin via desmoplakine
- - is linked to actin via ß-catenin
- TGFß
- - binds two different receptor proteins with one molecule
- - binds two different receptors with two molecules (dimer)
- - binds, in most cases, first with a type II receptor and then with a
type I receptor
- - activates a tyrosine protein kinase
- PKB has anabolic effects
- - by directly stimulating PKA
- - by facilitating ribosomal initiation and translocation
- - by facilitating phosphorylating of 4E-BP
- - by stimulating phosphorylase a
- PI 3-kinase is
- - both a protein kinase and an inositol lipid kinase
- - a lipid kinase that phosphorylates diacyglycerol into phosphatidic
acid
- - an essential component of the PKB signal transduction pathway
- - the immediate intracellular kinase associated with the insulin
receptor
- Members of the Rho family of GTPases are involved in
- - vesicle transport
- - cell cycle regulation
- - nuclear import and export
- - cytoskeletal organization
- Ras activators are
- - hSos
- - ras-GRF2
- - neurofibromin
- - PI 3-kinase
- A GTPase effector loop
- - has to be phosphorylated in order to allow access of substrate
- - is a short stretch of amino acids that interacts with downstream
effectors
- - changes conformation when GDP is replaced by GTP
- - interacts with the GTPase activating protein (GAP)
- GSK3ß
- - dephosphorylates and inactivates glycogen synthase
- - protects ß-catenin against its destruction by the S26 proteasome
- - is "inhibited" by the Wnt/Dsh signaling pathway
- - interacts with axin/APC
- GleevecTM
- - binds the EGF receptor and prevents ligand binding
- - competes with ATP to bind the Abl protein kinase
- - holds Abl in an inactive conformation
- - is used for lung cancer treatment
- Chromosome translocation can contribute to cancer because of
- - an increased number of copies of genes
- - a loss of regulation of activity of novel fusion proteins.
- - an elevated expression of certain genes (change of locus)
- - an unbalance in chromosomal length
- The SH2 domain
- - mediates SMAD oligomerization (SMAD2/4 complexes)
- - is a conserved domain first identified in Src
- - contains two pockets, one that binds phosphotyrosine and one that
binds a "specificity" amino acid(s)
- - plays an essential role in some receptor signaling complex
formations
More than one completion (answer) may be correct
Zero mistake 4 points, 1 mistake 2 points, 2 mistakes 1 point, more than 2
no points
|
ACKNOWLEDGMENTS
|
|---|
We acknowledge the French Ministry of Research and Higher Education, the
Region of Aquitaine, the Company of Biologists (United Kingdom), and the
University of Bordeaux-1 for their financial support of this event.
Address correspondence to: IJsbrand Kramer
(i.kramer{at}iecb.u-bordeaux.fr).
TOP
ABSTRACT
INTRODUCTION
