Systems Biology: Today and Tomorrow; the WTEC visit to The Netherlands

1. Systems Biology: Today and Tomorrow; the WTEC visit to The Netherlands The Institute for Molecular Cell Biology, BioCentre Amsterdam, Free University Amsterdam

2. The WTEC visit to The Netherlands:the program • 11:45 Welcome address (Hans Westerhoff): 12:15 Marvin Cassman: Aims of the WTEC study • 12:30 lunch13:15 Welcoming remarks by Pier Vellinga (Dean Faculty of Earth and Life Sciences) • 13:45-17:00 Examples of Dutch Systems Biology 16:40 Teaching Systems Biology • 16:50 Drinks 17:05 General discussion (chair: Roel van Driel): Systems Biology and its future • 17:45 Departure for the restaurant (De Molen; Amstelveen)

3. System Biology: Where it matters • International developments • European developments/potential • Dutch Systems Biology

4. What is/has been happening internationally? • Institutes (ISB-Seattle) [BCA/IMC here] • Conference (ICSB) • Electronic cells • Alliances

5. BioCentre Amsterdam and its Institute for Molecular Cell Biology • BCA: From Entering the living cell to Molecular Systems Biology • IMC:

6. The 4th International Systems Biology Conference 2004 in Heidelberg

7. Electronic cells • E-cell • Virtual cell • Silicon cell

8. www.siliconcell.net:Computer replica of parts of living cells (NL, SA, USA)

9. Bottom up international alliances • IEcA (International E. coli Alliance) • YSBN (Yeast Systems Biology Network) • EGF Signalling network

10. Round Table discussion 2: Developing a White Paper www.ieca2004.ca

11. IEcA status quo • Manifest being written • Genome Canada supports workshop funding organizations plus scientists to put together an international prokaryotic SB program • To prepare concrete action plan • Genome Canada looks for European partners (e.g. German SysMo) • US partner needed ……….

12. YSBN

13. YSBN

14. YSBN status quo • White paper has been written • Committees have been formed • Funding unclear

15. GF signalling alliance • In preparation only • Kholodenko, Goryanin (GSK)

16. System Biology: Where it matters • International developments • European developments/potential • Dutch Systems Biology

17. What is happening in Europe? • National programs • Germany (BMBF): • German Hepatocyte: Systeme des Lebens (20-50 ME); has begun • SysMo (Systems Biology of Microorganisms (10 ME); call in 2005 • Finland: System Biology and Bioinformatics (10.5 ME); has begun • The Netherlands: SBNL; set of organism focused programs (L. lactis, S. cerevisiae, E. coli, Silicon cell, Signal transduction, Xomics, Cell Biophysics, …..); some funded (IOP) most still in limbo • UK: BBSRC Integrative Biology 10 years program: > 6 national centres 5ME? each; bids (for first round) are now in • ….. • Transnational programs: • SysMO: Germany intends to have this as a transnational program (Germany, Austria, Netherlands, France?) • ERANET: • Brussels catalyzed transnational activity; inspired by SysMO? • Paris meeting August 26 (joint with EUSYSBIO meeting) • European programs:

18. Transnational initiatives; SysMo • German BMBF • Preparing for microbial System Biology program • Wants to go transnational • Austrian, Dutch ?partners • 2005: call for proposals

19. What is happening in Europe? • National programs • Germany (BMBF): • German Hepatocyte: Systeme des Lebens (20-50 ME); has begun • SysMo (Systems Biology of Microorganisms (10 ME); call in 2005 • Finland: System Biology and Bioinformatics (10.5 ME); has begun • The Netherlands: SBNL; set of organism focused programs (L. lactis, S. cerevisiae, E. coli, Silicon cell, Signal transduction, Xomics, Cell Biophysics, …..); some funded (IOP) most still in limbo • UK: BBSRC Integrative Biology 10 years program: > 6 national centres 5ME? each; bids (for first round) are now in • ….. • Transnational programs: • SysMO: Germany intends to have this as a transnational program (Germany, Austria, Netherlands, France?) • ERANET: • Brussels catalyzed transnational activity; inspired by SysMO? • Paris meeting August 26 (joint with EUSYSBIO meeting) • European programs:

20. What is happening in Europe? • European programs: • EU: FP6 (Specific Support Action EUSYSBIO; Computational Systems Biology not in third call; Synthetic Biology in April 2004 call) • EUREKA: • (New Safe Medicines Faster) • Virtual Cell • EMBO: SB in EMBL?? • ESF: Forward look, towards EUROCORE and more?

21. FP6: Specific Support Action EUSYSBIO • Get science policy makers together • Help organize ICSB2004 (Heidelberg, October 9-13 2004) • Organize SB course (FEBS): March 2005 • Set up ERANET: transnational funding possibilities • Set up European SB organization/group

22. WP8 (Dutch WP) deliverables • D26: Platform of excellent Eur SB groups: • -at ICSB form network of excellence? • D27: Workshop devoted to standards • At ICSB2004: October 10, Heidelberg (joint with ESF?) • D28: Strategy paper discussing scientific basis science policy planning • To be written on request of WP6 • D29: Scientific journal • A book on Defining Systems Biology for now

23. BioSim ( NoE): Mosekilde • Models for pharmaceuticals

24. BioSim ( NoE): Models only

25. FP6: Future • Computational Systems Biology: • Call for IP on Computational Systems Biology with deadline November 2004 failed (STREPS and Coordination Action remain) • Promises for 4th call and FP7 • Problem?: too dry …?…..

26. What is happening in Europe? • European programs: • EU: FP6 (Specific Support Action EUSYSBIO; Computational Systems Biology not in third call; Synthetic Biology in April 2004 call) • EUREKA: • (New Safe Medicines Faster) • InSysBio • EMBO: SB in EMBL?? • ESF: Forward look, towards EUROCORE and more?

27. EUREKA’s InSysBio: IMC’s relevance for Biomed and Biotech

28. EUREKA’s InSysBio: IMC connecting with European pharma & food industry

29. InSysBio:Eureka’s virtual cell initiative • European, industry driven research • Aim: Making computer models of living organisms for drug development etc. and • (now also:) for food production (biotech) • Bioinformatics • Tool development • Models for pharma and Models for food

30. ESF forward look • Study to see if System Biology could be ESF theme • This would then make ESF catalyze common research programmes between National science foundations

31. What is needed? • Wet SB, not just dry (FP6, EUREKA) • Try to get the national SFs to coordinate their SB programs • Construct mechanisms for transnational funding • Become partners for USA, Japan, Canada, China, Korea • Provide funding anchors for the alliances

32. System Biology: Where it matters • International developments • European developments/potential • Dutch Systems Biology

33. Dutch/EU SB:Integrative Systems Biology • Look at all the leaves • individually 2. The phenomena; top down Diagnosis; pattern recognition 3. Get to the roots; bottom up; Understanding of the special System properties/principles

34. Dutch Systems Biology:The Ambition • Ambition: • Not just ‘SB’; aim is to now understand living organisms from molecule to cell, organ, and human organism • Put a healthy man …. on earth Dutch Niche: • mechanistic (bottom up SB) • wet plus dry • industry plus academia Bring about ‘common goal’ synergism between national programs (European countries are too small for SB) • Generate superfund from Europe

35. What is happening in NL? • National programs • NWO (Dutch NSF) preludes (6 M$ each): • Bioinformatics • Molecule to Cell • Computational Biology • National Genomics Centres (200 M$): • Centre Medical Systems Biology (Leiden, VU, TNO; not really SB) • Kluyver Centre (some SB) • Plant Systems (not SB) • Cancer (not SB) • IBIVU: Integrative BioInformatics VU (3 M$) • IOP-Genomics: Vertical Genomics (2 M$) • Ecogenomics-BSIK (10 M$)

36. What is going to happen in NL? • National programs • SBNL; set of focused program proposals: • L. lactis (Kuipers, Teusink, Siezen, Hugenholz. …) • S. cerevisiae (Bakker, Teixeira, Pronk, Heijnen) • Silicon cell Amsterdam (-Stellenbosch, Blacksburg; Snoep) • SBNL: Industrial platform • Partner in Transnational SysMO • Partner in EUREKA • Attempt at National Program integrating top down with bottom up

37. WTEC study: Systems Biology, Network Behavior in Biological Systems • State of the art information on network behavior, also internationally • Research opportunities • Identify potential interagency collaborations • Identify potential international collaborations • Publish results of study

38. The WTEC visit to The Netherlands:the program • 11:15 Coffee, tea, cookies in G076 • 11:45 Welcome address (Hans Westerhoff): Dutch and European Systems Biology; where it might matter • 12:15 Marvin Cassman: The aims of the WTEC study • 12:30 lunch13:15 Welcoming remarks by Pier Vellinga (Dean Faculty of Earth and Life Sciences) • 13:20 Coffee + informal discussions

39. The WTEC visit to The Netherlands:the program • 11:15 Coffee, tea, cookies in G076 • 11:45 Welcome address (Hans Westerhoff): Dutch and European Systems Biology; where it might matter • 12:15 Marvin Cassman: The aims of the WTEC study • 12:30 lunch13:15 Welcoming remarks by Pier Vellinga (Dean Faculty of Earth and Life Sciences) • 13:20 Coffee + informal discussions

40. The WTEC visit to The Netherlands:the program • 13:45-16:40 Examples of Dutch Systems Biology 13:45 Barbara Bakker; Vertical genomics 14:00 Jurgen Haanstra: Network based drug design 14:15 Frank Bruggeman: Silicon cell as a tool for understanding regulation • 14:30 Jan Lankelma: Treating cancer: fighting a system • 14:45 Jorrit Hornberg: New principles of signal transduction • 15:00:Tea

41. The WTEC visit to The Netherlands:the program • 15:30 Systems Biology in Delft: Wouter van Winden • 16:30 Lactococcus lactis faster; a Systems Biology endeavor; Bas Teusink • 16:40 Teaching Systems Biology, Hans V. Westerhoff • 16:50 Drinks 17:05 General discussion (chair: Roel van Driel): Systems Biology and its future • 17:45 Departure for the restaurant (De Molen; Amstelveen)18:00 Dinner. • 19:45 Departure for the airport • 20:00 Check in; KLM; Schiphol airport • 21:05 flight to the UK......

42. The WTEC visit to The Netherlands:the program • 15:30 Systems Biology in Delft: Wouter van Winden • 16:30 Lactococcus lactis faster; a Systems Biology endeavor; Bas Teusink • 16:40 Teaching Systems Biology, Hans V. Westerhoff • 16:50 Drinks 17:05 General discussion (chair: Roel van Driel): Systems Biology and its future • 17:45 Departure for the restaurant (De Molen; Amstelveen)18:00 Dinner. • 19:45 Departure for the airport • 20:00 Check in; KLM; Schiphol airport • 21:05 flight to the UK......

43. Orchestration of cellular processes in a simple cell: making Systems Biology work for Lactococcus lactis Bas Teusink Kluyver Centre (Hugenholtz,  Heijnen) RUG (Kuipers, Kok, Jansen, Poolman) VU (Westerhoff, Bakker, Snoep) CMBI (Siezen,Teusink) WCFS (Kleerebezem, Molenaar, de Vos) UvA (Brul, Hellingwerf, Breit) TNO-Food (Van der Werf, Smilde)

44. Evolution acts on the biological constraints: T = 37 °C T = 30 °C Objective: use Systems Biology to understand the limits of growth of Lactococcus lactis Limits of growth (at a given condition): -biological and physico-chemical constraints

45. Reference state: the pH-auxostat - Possible to operate stably at maximal growth rate - Study pH stress

46. WP1 Experimental design and method development Experimental protocols Hypothesis and prediction Applications WP4 Data management WP5 Translation and comparison to other biological systems WP3 Model building WP2 Experimental data acquisition Experimental data Overview of work packages

47. Overview of consortium members 1. Kluyver Centre (Hugenholtz,  Heijnen): metabolome, proteome, modelling, metabolic engineering, fermentations 2. RUG (Kuipers, Kok, Jansen, Poolman): transcriptome, protein, membrane proteome, protein interactions, bioinformatics, statistics, model building 3. VU (Westerhoff, Bakker, Snoep): kinetic modelling, integrative bioinformatics, metabolome, activity-proteome, transport, hierarchical control analysis 4. CMBI (Siezen, Teusink): bioinformatics, comparative genomics, genome mining, metabolic reconstruction

48. Overview of consortiummembers 5. WCFS (Kleerebezem, Molenaar, de Vos): regulation, mining, bioinformatics, metabolic engineering, metabolomics 6. UvA (Brul, Hellingwerf, Breit): DNA-array technology, signal transduction, experimental design 7. TNO-Food (Van der Werf, Smilde): metabolome, data analysis, experimental design

49. The WTEC visit to The Netherlands:the program • 15:30 Systems Biology in Delft: Wouter van Winden • 16:30 Lactococcus lactis faster; a Systems Biology endeavor; Bas Teusink • 16:40 Teaching Systems Biology, Hans V. Westerhoff • 16:50 Drinks 17:05 General discussion (chair: Roel van Driel): Systems Biology and its future • 17:45 Departure for the restaurant (De Molen; Amstelveen)18:00 Dinner. • 19:45 Departure for the airport • 20:00 Check in; KLM; Schiphol airport • 21:05 flight to the UK......

50. Teaching Systems Biology • Masters • Ph D students