Spatiotemporal dynamics of cell signalling
30 Sept - 3 Oct, 2010
Oslo, Norway

Organisers:

Draft Report

Summary

The FEBS and ESF co-sponsored workshop on ‘Spatiotemporal Dynamics of Cell Signalling' was held in Oslo, Norway end September-early October with 105 participants. The objectives of organising this workshop were 1) to arrange a small but excellent and topical international meeting in the field of compartmentalised signal transduction and a particular focus on the current and timely topic of dynamics and signaling systems which uses systems biology to integrate numerous data sets and parallel signaling events into an overall integrated network of signals 2) contribute to scientific interaction and update of European researchers in this area 3) educate Ph.D. students and post-docs that will have the opportunity to meet internationally well recognised researchers in the area and also to present their own data 4) promote and increase networking and concerted action in this research field in Europe and internationally.

The objective of the workshop was to address spatiotemporal organisation of signalling and the use of systems biology to integrate numerous data sets and parallel signalling events into an overall integrated understanding of networks of signals. The workshop featured 24 talks and 11 selected short talks with speakers from across Europe and from the US. Furthermore, over 50 posters were presented in lively sessions with much discussion and facilitating interactions between participants at all levels. Highlights of the programme were Opening Lectures by Sir Philip Cohen, John Scott and Susan Taylor on interaction networks and dynamics of signalling, respectively, as well as Key note Lectures by Tony Pawson, Tony Hunter and Martin Lohse on docking and anchoring, kinases and G-protein coupled receptors. The programme continued by sessions on immune cell signalling, mitogenic signalling, trafficking of signal proteins and signal termination. Signal regulation of polarisation and migration in normal and cancer cells was discussed as well as cardiovascular and metabolic signal processes and their dynamics.

Scientific Content

Thursday September 30th

Kjetil Tasken (Univ. of Oslo, Norway) opened the workshop by giving a brief overview of the history of the meeting and an outline of the lectures. This session continued with the first of three outstanding keynote speakers, Dr. John Scott ( Univ. of Washington, USA) presenting “Cell signalling in space and time”. In particular, he talked about the Erk1/2 pathway and demonstrated that AKAP-Lbc interacts directly with KSR-1 (Kinase Suppressor of Ras), forming a core of an Erk signalling network where several kinases (Ras, Raf, Mek and Erk) are brought in close proximity to each other. The second keynote speaker, Dr. Susan Taylor (University of California, San Diego, USA) introduced “Dynamics of signalling by PKA” and focused on how PKA is regulated by cAMP and how the tetrameric holoenzyme anchores to AKAPs. Sir Philip Cohen (University of Dundee, Scotland) gave the last keynote lecture “The interplay between protein phosphorylation and protein ubiquitylation in regulating the innate immune system”. Sir Cohen is interested in how signalling pathways that control the innate immune system are regulated during infection and how they trigger the production of pro-inflammatory cytokines and interferons.

Friday October 1st

Session II: Dynamics of Cell Signal Systems was chaired by Dr. John Scott and the first talk was given by Dr. Michael Yaffe (Massachusetts Institute of Technology, Boston, USA) about “Dynamics of protein kinase signalling in the DNA damage response”. Dr. Yaffe described how cells activate complex signalling pathways in response to DNA damage and how these pathways control e.g. cell cycle progression. A systems biology approach to DNA damage signalling revealed new pathways and molecular events important for the damage response. In addition, the approach demonstrated that signalling outcome from a specific kinase is context-dependent, determining if the cell should enter cell cycle arrest or die. Dr. Yaffe was followed by Dr. Audrey Clapéron (INSERM, Paris, France) giving the short talk “EBP50, a scaffold protein, regulates negatively EGFR signalling in cancer biliary epithelial cells” focussing on how EBP50 can be critical for cancer progression. The talk was followed by a presentation on “Tyrosine kinase signalling in space and time” by Dr. Margaret Frame (University of Edinburgh, Scotland) where she focused on Src and FAK (focal adhesion kinase) signalling in relation to cancer and addressed the important question of whether agents that target adhesion regulators have anti-invasive or anti-metastatic activity. The session was continued by Dr. Peter Jordan (National Health Institute Ricardo Jorge, Lisboa, Portugal) presenting the short talk “Protein kinases WNK4 and SYK constitute a signalling pathway regulating cell surface expression of CFTR”. The background for this talk was the discovery that mutations in WNK1 or WNK4 causes familial hypertension and the identification of a role for WNK1/4 in the regulation of the chloride channel CFTR. The session ended with Dr. Igor Stagljar (University of Toronto, Canada) presenting “Protein Interaction Networks regulating cell signalling in human health and disease”. In his talk, Dr. Stagljar talked about receptor tyrosine kinases (RTKs) and the application of MYTH screening of human RTKs.

Session III: Spatiotemporal organization of Ras-Raf-MAP kinase signalling cascades was chaired by Dr. Fritz Herberg (University of Kassel, Germany) who introduced the first speaker Dr. Philippe Bastiaens (Max-Planck-Institute for Molecular Physiology, Dortmund, Germany) presenting “The spatial organisation of Ras signalling: structure, dynamics and spatial organisation”. Dr. Bastiaens started his talk by explaining how spatial organisation of Ras signalling systems is maintained in the cell. In the second part of the talk, the question of how spatial organisation of Ras signalling systems affects signal responses was addressed. The next speaker was Dr. Andre Limnander (University of California, San Fransisco, USA) who gave the short talk “Stim1and PKC d set a threshold for pro-apoptotic Erk signalling during B cell development”. In mature B cells, cross-linking of the BCR leads to proliferation and activation whereas it triggers apoptosis in immature B cells. Dr. Limnander explained that the amplitude and duration of the BCR-induced Ca2+ entry is higher in immature than in mature B cells and described signalling pathways involved in the apoptosis vs. proliferation decision. In more detail, he demonstrated that BCR cross-linking activates 2 different pathways to Erk activation. The talk was followed by a presentation on “Ras and Raf signalling in melanoma: biology and therapies” by Dr. Richard Marais (Institute of Cancer Research, London, UK). Erk signalling (Ras-Raf-MEK-Erk) has been shown to be hyper-activated in more than 90% of melanomas. Dr. Marais described how the cGMP-specific phosphodiesterase PDE5A which is the target for drugs like Viagra and Cialis, is strongly down-regulated in a number of melanoma cell lines and in patient samples and that the melanoma mutant V600EB-Raf suppresses PDE5A expression. Closing this session Dr. Roger Davis (University of Massachusetts, Boston, USA) gave a talk on “Signal transduction by stress-activated MAP kinases” where he focused on MAP kinase pathways and in particular on JNK. More specifically, Dr. Davis presented data from mouse experiments revealing that JNK is required for K-Ras-mediated tumorigenesis, resulting in lung tumor formation in vivo. The role of JNK seems to be cell type dependent and JNK can function both as a tumor suppressor or be required e.g. in hepatocellular carcinoma (HCC). In conclusion, JNK plays a mechanistically-based role in cancer but can have both pro- or anti-tumorigenic functions.

Keynote lecture 4: Dr. Peter Downes (University of Dundee, Scotland) introduced Dr. Tony Hunter (Salk Institute, San Diego, USA) who presented a keynote lecture entitled “Signal transduction in cancer and DNA damage”. Initially, Dr. Hunter tried to answer the fundamental question of why phosphate-containing compounds are so frequently used by biological systems. Later, he focused on studies of the protein serine/threonine kinase DAPK3 which has been found to be mutated in certain cancers affecting for instance breast or lung. All the three mutations he described (T112M, D161N, P216S) have a negative impact on the kinase activity, and while wild-type DAPK3 induces cell cycle arrest and apoptosis, the cancer-associated mutants do not. He proposed that the mutants can suppress the activity of wild-type DAPK3 in vivo through a dominant negative effect. Next, he talked about how certain kinases in cancer cells acquire loss-of-function mutations to act as tumor suppressors and protein kinase C b 2 was used as an example. Finally, he presented data on the tumor suppressor CtIP and its role in DNA repair after induction of double-strand breaks by laser scissors.

Session IV: Signal Systems for Immune Cell Activation, kindly sponsored by Bristol-Myers Squibb was chaired by Dr. Kjetil Tasken (Biotechnology Centre of Oslo, Norway). The first presenter was Dr. Art Weiss (University of California San Francisco, USA) with a talk entitled “Regulating antigen receptor induced tyrosine phosphorylation”. He described how the function of different protein tyrosine kinases in T cells can be studied with an allele specific inhibitor system. The next presentation was a short talk by Marek Cebecauer (Imperial College London, UK) on the topic “Spatio-temporal organisation of signalling molecules in activated T lymphocytes”. He discussed signalling complexes and clusters and described how clusters can be analyzed with diffusion maps in order to discern between mobile and constrained clusters. The following speaker was Rose Zamoyska (University of Edinburgh, Scotland) with a talk entitled “T cell receptor proximal signalling”. She reported the generation of mice where the unique domains of Fyn and Lck in thymocytes have been swapped. Thymocytes from mice expressing Lck containing a Fyn unique domain (Fu-Lck mice) fails to proliferate and differentiate as long as wild-type Lck is absent (but with wild-type Fyn present. The next speaker was Dr. Yenan Bryceson (Karolinska University Hospital Huddinge, Stockholm, Sweden) with the short talk “Orai1-mediated calcium influx is required for cytotoxic lymphocyte degranulation and target cell lysis”. He reported analyses of NK cells obtained from an Orai1 deficient patient and demonstrated that Orai1 is necessary for calcium influx, target cell recognition, NK cell cytotoxicity and cytokine production, but not for adhesion and granule polarization. The session was concluded by Dr. Andrey Shaw (Washington University, Saint Louis, USA) who presented “Imaging T cell activation”. He focused on KSR which can bind Ras/Mek/Erk. KSR deficient T cells reveal defective Erk activation, and Dr. Shaw demonstrated that KSR/Erk localise to the immunological synapse (IS) where KSR is necessary for Erk-mediated phosphorylation of stathmin.

Saturday October 2nd

Keynote lecture 5: Dr. Carl-Henrik Heldin introduced Dr. Tony Pawson (Samuel Lunefeld Research Institute, Canada) presenting “Modular protein domains in cell signalling”. Dr. Pawson addressed the mechanisms underlying intracellular signal transduction with focus on modular proteins that mediate protein-protein interactions with particular focus on the SH2 domain function and the regulation of tyrosin kinases in signalling events. Dr. Pawson also focused on methyl group binding TUDOR domains and presented data showing that some TUDOR domains get enhanced substrate specificity by flanking sequences. The TUDOR domain containing Trdr group of proteins that are required for germline development contain such flanking sequences.

Session V: Dynamics of Phospholipid and Cyclic Nucleotide Signalling was chaired by Dr. Anders Tengholm (Uppsala University, Swedan) and the first talk entitled “New tools to study phospholipid signaling in the endocytotic pathway” was given by Dr. Carsten Schultz (EMBL, Heidelberg, Germany). Dr. Schultz showed how to partially activate signalling networks by the use of permanent modulators. EGF signalling activates kinases via elevated PIP3 levels and through a signalling cascade involving endosomes leads to PIP degradation. The talk was followed by Dr. Viacheslav Nikolaev (Georg August University Medical Center, Goettingen, Germany) presenting the talk “Analysis of subcellular cAMP compartmentation and beta-adrenergic receptor distribution in cardiomyocytes by novel SICM/FRET”. Dr. Nikolaev used scanning ion conductance microscopy (SICM) to investigate the ß1 and ß2 receptor distribution and observed that in normal cardiomyocytes, ß2 is effective in the T-tubule but not in the crest. The next speaker was Dr. Peter Downes (University of Dundee, Scotland) presenting “PI3 Kinase signaling in Human Cancer”. PTEN is involved in epithelial integrity and direct cell movement, and Dr. Downes showed that PTEN prevent mesenchymal to endothelial migration and that the PTEN mutation Y138C is found in small cell lung carcinomas. Furthermore, Dr. Downes indicated that PTEN protein and lipid phosphorylation together suppress cell invasion. Dr. Downes concluded that their results indicate the presence of an Akt-independent PTEN regulated pathway. Dr. Barbara Brandhuber (Array BioPharma Inc., Boulder CO, USA) continued the session with her talk entitled “Crystal structure of AKT1 containing both the plecstrin homology and kinase domains bound to the allosteric AKT inhibitor VIII reveals a new mode of kinase inhibition and regulation”. The Akt pathway is frequently dysregulated in human cancer, and several clinical trials are testing Akt pathway inhibitors as cancer treatment. The session closed with Dr. Klaus Okkenhaug (Babraham Institute, Cambridge, England) presenting “PI3K signalling in lymphocytes”. Dr. Okkenhaug talked about control of ß cell development through the B cell receptor (BCR), particular in regard to the PI3K isoforms P110a, P110ß and P110d. Previous studies revealed a role for P110d in agonist-induced BCR signalling. Dr. Okkenhaug showed that in the absence of P110d, P110a but not P110ß could compensate for P110d in the process of early B cell development and B cell survival in the spleen.

Session VI: Control of Migration, Adhesion and Polarity was introduced by chair Dr. Johannes Bos (University of Utrecht, The Netherlands) and opened with Dr. Christopher Marshall (Institute of Cancer research, London, England) with a presentation on “Kinase and GTPase Signalling Pathways Controlling Cell Movement”. Dr. Marshall focused on the Rho-ROCK pathway and the transition from mesenchymal (elongated) to amoboid (rounded) motility. Dr. Marshall described 2D and 3D cell assays to study the mesenchymal to amoboid motility and indicated that proteins required for 2D movement like RAC and Rho F suppress 3D movement and vice versa. This indicates presence of distinct mechanisms driving 2D and 3D cell movement. The talk was followed by Dr. Gregor Reither (EMBL Heidelberg, Germany) that gave a talk entitled “Modulation and visualisation – Epac's impact on calcium”. Dr. Reither focused on Epac's impact on cellular calcium levels and described a model designed to predict the in vivo situation. The goal was to get as close resemblance as possible between modelled and measured data, and Dr. Reither used live cell imaging to visualize Epacs impact on calcium in the cell. The session continued with Dr. Ruth Palmer (Umeå University, Sweden) talking about “Anaplastic Lymphoma Kinase Signalling in Drosophila”. Dr. Palmer showed that Alk, a receptor tyrosine kinase, is required for visceral muscle development. Alk signalling is also required for gut muscle and endoderm development through activation of SMAD via dpp (TGFß). The next speaker, Dr. Sara Hopkins (University College London, UK) gave a talk entitled “Mig6 is a sensor of EGF deprivation that triggers c-Abl induced apoptosis during epithelial morphogenesis”. The last talk of this session by Dr. Johannes L. Bos (University of Utrecht, The Netherlands) was entitled “Spatial and temporal control of Rap in signalling”. Treatment with the cAMP analogue 007 activates Rap and integrin-mediated adhesion and spreading. Dr. Bos showed that RanBP2 knockdown also induces Rap1 activity and cell adhesion and demonstrated that in this case Epac1 is not localised in the nuclear envelope anymore.

Sunday October 3rd

Keynote lecture 6: Dr. Finn Olav Levy (University of Oslo, Norway) introduced the last key note lecture given by Dr. Martin Lohse (University of Würzburg, Germany) who talked about “Dynamics of live G protein-coupled receptor signalling”. In his presentation Dr. Lohse demonstrated how the problem of visualising signalling in real time with spatial information could be addressed by using both intra- as well as intermolecular FRET assays. Dr. Lohse first discussed data from intramolecular FRET assays allowing measurements of the conformational switch of GPCRs in real time. He reported that different receptors have different switch times ranging from 1 ms in the case of rhodopsin up to minutes in the case of isolated receptors. Furthermore, the switch time of an individual receptor strongly depends on the stimulating agent, with full agonists inducing the fastest and inverse agonists the slowest switch.

Session VII: Dynamic Organization of Normal and Cancer Cell Signalling was chaired by Dr. Jacques Pouyssegur (University of Nice, France) introducing the first speaker Dr. Carl-Henrik Heldin (Ludwig Institute for Cancer Research, Uppsala, Sweden) presenting a talk entitled “Signaling via TGF-ß receptors in health and disease.” After a short description of the type I and II TGF-ß receptors and the Smad signalling pathways Dr. Heldin introduced PARP1 (poly (ADP-ribose) polymerase 1, known to be important for DNA damage response) as a novel factor able to shut down Smad signalling. PARP1 binds the Smad3/4 transcription factor complex, PARylates (poly ADP-ribosylation) Smad4 and thereby dissociates it from the DNA. This presentation was followed by “Spatiotemporal analysis of epidermal growth factor in cellular signalling and squamous cell carcinoma”, a short talk given by Dr. Fiona Simpson (University of Queensland, Brisbane, Australia). Dr. Simpson first discussed EGF receptor trafficking and introduced hook-related protein 1 (HkRP1) as a crucial factor, showing that a mutated version of HkRP1 traps the EGFR in early endosomes. The next speaker was Dr. Ivan Dikic (University of Frankfurt, Germany) with: “Dynamics of ubiquitin signaling networks”. In his presentation Dr. Dikic focused on the role of ubiquitin in the activation of NF-?B. Based on structural data he first demonstrated that NEMO, the regulatory component of the I?B kinase (IKK) complex, binds linear ubiquitin chains. Dr. Dikic was followed by a short talk: “The role of E3 ligase TRAF6 in TGF-ß signal transduction in prostate cancer” by Dr. Reshma Sundar (Umeå University, Sweden). Starting with a short introduction about TGF-ß signalling she presented TRAF6 as a part of the non-canonical pathway resulting in the p38 pathway. The final talk of the meeting was given by this session's chair Dr. Jacques Pouyssegur about: “Hypoxia signaling and tumor progression”. In his presentation Dr. Poussyegur first gave an introduction about hypoxic induction of the transcription factor HIF-1 and the consequent glycolysis, resulting in a challenge for the intracellular pH homeostasis system in hypoxic cells.

Poster session
A total of 53 posters were presented during the poster session. The posters were of high scientific quality which facilitated exciting discussions between the presenters and the participators. All posters were also evaluated by a poster-award committee consisting of Dr. Ruth Palmer, Dr. Klaus Okkenhaug and Dr. Igor Stagljar, who announced three winners of the poster awards (receiving gift cards of values 600, 350, and 350 NOK, respectively):

Best poster: Radtke S., Wuller S., Yang X., Lippok B. E., Mutze B., Schmitz-Van de Leur H., Schaper F. and Hermanns H. M.: “Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation.”

First runner up posters: Chymkowitch P., Eldholm V., Zimmermann C., Sommerfelt A., Wittenberg C. and Enserink J. M.: “Cdk1 functions in a network of CDK's that regulate transcription to exert a novel level of cell cycle control.”

Cornez I., Mosenden R., Singh P., Rahmouni S., Moutschen M. and Tasken K.: “Disruption of type 1 protein kinase A anchoring in mouse T cells induces enhanced immune responsiveness.”

Programme

Thursday, September 30
17:00-19:30 Session I: Opening Remarks and Overview, Keynote lectures 1-3, Chair: Kjetil Taskén
17:00-17:10 Introduction to joint session and opening of Workshop on Spatiotemporal Dynamics of Cell Signalling
17:10-17:55 John D. Scott, University of Washington, Seattle, Washington, USA. Title: “Cell signaling in space and time”
17:55-18:00 Discussion
18:00-18:45 Susan S. Taylor, University of California San Diego, San Diego, California, USA. Title:“Dynamics of PKA Signaling”
18:45-18:50 Discussion
18:50-19:35 Sir Philip Cohen, University of Dundee, Dundee, Scotland. Title: "The interplay between protein phosphorylation and protein ubiquitylation in regulating the innate immune system"
19:35-19:40 Discussion
20:00 Dinner
22:00 Poster viewing

Friday, October 1
08:30 Session II: Dynamics of Cell Signal Systems , Chair: John Scott
08:30-08:55 Mike Yaffe, Massachusetts Institute of Technology, Boston. Title: "Dynamics of Protein Kinase Signaling in the DNA Damage Response"
08:55-09:00 Discussion
09:00-09:10 Short talk: Audrey Clapéron, INSERM, Paris, France. Title: “EBP50, a scaffolding protein, regulates negatively EGFR signalling in cancer biliary epithelial cells”
09:10-09:15 Discussion
09:15-09:40 Margaret Frame, University of Edinburgh, Scotland. EACR speaker. Title: "Tyrosine kinase signalling in space and time”
09:40-09:45 Discussion
09:45-09:55 Short talk: Peter Jordan, National Health Institute Ricardo Jorge, Lisboa, Portugal. Title: “Protein kinases WNK4 and SYK constitute a signalling pathway regulating cell surface expression of CFTR”
09:55-10:00 Discussion
10:00-10:25 Igor Stagljar, University of Toronto, Toronto, Canada. Title: "Protein Interaction Networks Regulating Cell Signaling in Human Health and Disease”
10:25-10:30 Discussion
10:30 Coffee / Tea

11:00 Session III: Spatiotemporal Organization of Ras-Raf-MAP Kinase Signaling Cascades ,
Chair: Friedrich W. Herberg
11:00-11:25 Philippe Bastiaens, Max-Planck-Institute for Molecular Physiology, Dortmund, Germany. Title:“The spatial organization of Ras signalling”
11:25-11:30 Discussion
11:30-11:40 Short talk: Andre Limnander, University of California at San Francisco, San Francisco, CA, USA. Title: “Stim1 and PKCd set a threshold for pro-apoptotic Erk singaling during B cell development
11:40-11:45 Discussion
11:45-12:10 Richard Marais, Institute of Cancer Research, London, England. Title: “RAF signaling in melanoma”
12:10-12:15 Discussion
12:15-12:40 Roger Davis, University of Massachusetts, Boston, USA. Title: “Signal transduction by stress- activated MAP kinases”
12:40-12:45 Discussion
13:00 Lunch
14:00-17:00 Poster session

17:00 Keynote lecture 4 , Chair: Peter Downes
Tony Hunter, Salk Institute, San Diego, California, USA. Title: "Signal transduction in cancer and DNA damage"
17:45 Coffee / Tea

18:00 Session IV: Signal Systems for Immune Cell Activation , Chair: Kjetil Tasken, Sponsored by Bristol- Myers Squibb
18:00-18:25 Art Weiss, University of California San Francisco, San Francisco, California, USA. Title:“Regulating Antigen Receptor Induced Tyrosine Phosphorylation”
18:25-18:30 Discussion
18:30-18:40 Short talk: Marek Cebecauer, Imperial College London, London, UK. Title: "Spatio-temporal organisation of signalling molecules in activated T lymphocytes"
18:40-18:45 Discussion
18:45-19:10 Rose Zamoyska, University of Edinburgh, Edinburgh, Scotland. Title: “T-cell receptor proximal signaling”
19:10-19:15 Discussion
19:15-19:25 Short talk: Yenan Bryceson, Karolinska University Hospital Huddinge, Stockholm, Sweden. Title: “Oral1-mediated calcium influx is required for cytotoxic lymphocyte degranulationa and target cell lysis”.
19:25-19:30 Discussion
19:30-19:55 Andrey S. Shaw, Washington University, Saint Louis, Missouri, USA. Title: “Imaging T-cell activation”
19:55-20:00 Discussion
20:00 Dinner
22:30 Hot topics poster award

Saturday, October 2
08:30 Keynote lecture 5 , Chair: Carl-Henrik Heldin
Tony Pawson, Sam Lunenfeld Research Institute, Toronto, Canada. Title: “Modular protein domains in cell signaling”
09:15 Coffee / Tea

09:30 Session V: Dynamics of Phospholipid and Cyclic Nucleotide Signaling , Chair: Anders Tengholm
09:30-09:55 Carsten Schultz, EMBL, Heidelberg, Germany. Title: “New tools to study phospholipid signaling in the endocytotic pathway”
09:55-10:00 Discussion
10:00-10:10 Short talk: Viacheslav Nikolaev, Georg August University Medical Center, Goettingen, Germany. Title: “Analysis of subcellular cAMP compartmentation and beta-adrenergic receptor distribution in cardiomyocytes by novel SICM/FRET technique”
10:10-10:15 Discussion
10:15-10:40 Peter Downes, University of Dundee, Dundee, Scotland. Title: "Dynamic regulators of PTEN function as tumor suppressors and oncogenes"
10:40-10:45 Discussion
10:45-10:55 Short talk: Barbara Brandhuber, Array BioPharma Inc., Boulder, CO, USA. Title: “Crystal structure of AKT1 containing both the pleckstrin homology and kinase domains bound to the allosteric AKT inhibitor VIII reveals anew mode of kinase inhibition and regulation”.
10:55-11:00 Discussion
11:00-11:25 Klaus Okkenhaug, Babraham Institute, Cambridge, England. Title: “PI3K signalling in lymphocytes”
11:25-11:30 Discussion
12:00 Lunch

13:00 Session VI: Control of Migration, Adhesion and Polarity , Chair: Johannes L. Bos
13:00-13:25 Christopher Marshall, Institute of Cancer Research, London, England. Title: “Kinase and GTPase Signalling Pathways Controlling Cell Movement”
13:25-13:30 Discussion
13:30-13:40 Short talk: Gregor Reither, Cell Biology and Biophysics Unit, EMBL Heidelburg, Germany.
Title: “Modelling and visualisation – Epac's impact on calcium”
13:40-13:45 Discussion
13:34-14:10 Ruth Palmer, Umeå University, Umeå, Sweden. Title: “Anaplastic Lymphoma Kinase signaling
in Drosophila”
14:10-14:15 Discussion
14:15-14:25 Short talk: Sarah Hopkins, University College London, London, UK. Title: “Mig6 is a sensor of EGF deprivation that triggers c-Abl induced apoptosis during epithelial morphogenesis”
14:25-14:30 Discussion
14:30-14:55 Johannes L. Bos, University of Utrecht, Utrecht, The Netherlands. Title: “Spatial and temporal control of Epac1 in cell adhesion”
14:55-15:00 Discussion
16:30 Excursion
19:00 Dinner

Sunday, October 3
09:00 Keynote lecture 6 , Chair: Finn Olav Levy
Martin Lohse, University of Würzburg, Würzburg, Germany. Title: “Dynamics of live G protein- coupled receptor signaling”
10:00 Coffee / Tea

10:30 Session VII: Dynamic Organization of Normal and Cancer Cell Signaling Chair: Jacques Pouyssegur
10:30-10:55 Carl-Henrik Heldin, Ludwig Institute for Cancer Research, Uppsala, Sweden. EACR speaker.
Title: “Signaling via PDGF and TGF-beta receptors in health and disease”
10:55-11:00 Discussion
11:00-11:10 Short talk: Fiona Simpson, The University of Queensland Diamantina Inst., Brisbane, Australia. Title: “Spatiotemporal analysis of epidermal growth factor in cellular signalling and in squamous cell carcinoma”
11:10-11:15 Discussion
11:15-11:40 Ivan Dikic, University of Frankfurt, Frankfurt, Germany. Title: “Dynamics of ubiquitin signaling networks”
11:40-11:45 Discussion
11:45-11:55 Short talk: Reshma Sundar, Umeå University, Umeå, Sweden. Title: “The role of E3 ligase TRAF6 in TGF-ß signal transduction in prostate cancer”
11:55-12:00 Discussion
12:00-12:25 Jacques Pouyssegur, University of Nice, Nice, France. Title: ”Hypoxia Signaling and Tumor progression”
12:25-12:30 Discussion
12:30 Lunch – Departure