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

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Systems biology today and tomorrow the wtec visit to the netherlands l.jpg

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

The Institute for Molecular Cell Biology, BioCentre Amsterdam, Free University Amsterdam


The wtec visit to the netherlands the program l.jpg
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)


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System Biology: Where it matters

  • International developments

  • European developments/potential

  • Dutch Systems Biology


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What is/has been happening internationally?

  • Institutes (ISB-Seattle) [BCA/IMC here]

  • Conference (ICSB)

  • Electronic cells

  • Alliances


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BioCentre Amsterdam and its Institute for Molecular Cell Biology

  • BCA: From Entering the living cell to Molecular Systems Biology

  • IMC:


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The 4 Biologyth International Systems Biology Conference 2004 in Heidelberg


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Electronic cells Biology

  • E-cell

  • Virtual cell

  • Silicon cell


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


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Bottom up international alliances Biology

  • IEcA (International E. coli Alliance)

  • YSBN (Yeast Systems Biology Network)

  • EGF Signalling network


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Round Table discussion 2: Biology

Developing a White Paper

www.ieca2004.ca


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IEcA status quo Biology

  • 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 ……….


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YSBN Biology


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YSBN Biology


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YSBN status quo Biology

  • White paper has been written

  • Committees have been formed

  • Funding unclear


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GF signalling alliance Biology

  • In preparation only

  • Kholodenko, Goryanin (GSK)


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System Biology: Where it matters Biology

  • International developments

  • European developments/potential

  • Dutch Systems Biology


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What is happening in Europe? Biology

  • 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:


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Transnational initiatives; SysMo Biology

  • German BMBF

  • Preparing for microbial System Biology program

  • Wants to go transnational

  • Austrian, Dutch ?partners

  • 2005: call for proposals


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What is happening in Europe? Biology

  • 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:


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What is happening in Europe? Biology

  • 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?


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FP6: Specific Support Action EUSYSBIO Biology

  • 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


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WP8 (Dutch WP) deliverables Biology

  • 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


  • Biosim noe mosekilde l.jpg
    BioSim ( NoE): Mosekilde Biology

    • Models for pharmaceuticals



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    FP6: Future Biology

    • 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 …?…..


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    What is happening in Europe? Biology

    • 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?


    Eureka s insysbio imc s relevance for biomed and biotech l.jpg
    EUREKA’s InSysBio: BiologyIMC’s relevance for Biomed and Biotech



    Insysbio eureka s virtual cell initiative l.jpg
    InSysBio: food industryEureka’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


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    ESF forward look food industry

    • Study to see if System Biology could be ESF theme

    • This would then make ESF catalyze common research programmes between

      National science foundations


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    What food industryis 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


    System biology where it matters32 l.jpg
    System Biology: Where it matters food industry

    • International developments

    • European developments/potential

    • Dutch Systems Biology


    Dutch eu sb integrative systems biology l.jpg
    Dutch/EU SB: food industryIntegrative 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


    Dutch systems biology the ambition l.jpg
    Dutch Systems Biology: food industryThe 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


    What is happening in nl l.jpg
    What is happening in NL? food industry

    • 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$)


    What is going to happen in nl l.jpg
    What is going to happen in NL? food industry

    • 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


    Wtec study systems biology network behavior in biological systems l.jpg
    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


    The wtec visit to the netherlands the program38 l.jpg
    The WTEC visit to The Netherlands: Systemsthe 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


    The wtec visit to the netherlands the program39 l.jpg
    The WTEC visit to The Netherlands: Systemsthe 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


    The wtec visit to the netherlands the program40 l.jpg
    The WTEC visit to The Netherlands: Systemsthe 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


    The wtec visit to the netherlands the program41 l.jpg
    The WTEC visit to The Netherlands: Systemsthe 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......


    The wtec visit to the netherlands the program42 l.jpg
    The WTEC visit to The Netherlands: Systemsthe 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......


    Slide43 l.jpg

    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)


    Slide44 l.jpg

    Evolution acts on the biological constraints: Systems Biology work for

    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


    Slide45 l.jpg

    Reference state: the pH-auxostat Systems Biology work for

    - Possible to operate stably at maximal growth rate

    - Study pH stress


    Slide46 l.jpg

    WP1 Systems Biology work for

    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


    Slide47 l.jpg

    Overview of consortium members Systems Biology work for

    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


    Slide48 l.jpg

    Overview of consortium Systems Biology work for members

    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


    The wtec visit to the netherlands the program49 l.jpg
    The WTEC visit to The Netherlands: Systems Biology work for 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......


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    Teaching Systems Biology Systems Biology work for

    • Masters

    • Ph D students


    Topmaster biomolecular integration systems biology l.jpg
    TopMaster Systems Biology work for Biomolecular Integration/Systems Biology

    The real cell

    The silicon cell

    Experiments

    Calculations

    Ultrafast space- and time-resolved spectroscopy, single molecule biophysics and biochemistry, chemistry of complex molecules, molecular genetics in living cells, intracellular networks, hierarchical control analysis, Integrative bioinformatics, principles of Systems Biology, entering the living cell, Silicon Cell, Integrative genomics, confocal microscopy, tumor cell biology, medical Systems Biology, signal transduction, nanotechnology, computational biology, ecological control analysis

    Transnational student projects

    Career development support

    International peer group

    Connected Ph D studentships

    Nature 427, 568

    A Master’s of the CRbCS

    Centre for Research on bioComplex Systems

    Enquiries:

    Prof. Dr. H.V. Westerhoff

    Telephone +31 20 444 7228

    E-mail: [email protected]


    Top bmi sb aims continued l.jpg
    TOP-BMI/SB Systems Biology work for : Aims continued:

    • obtain expertise in advanced conceptual and modeling methodologies for bioinformation and computing technologies, such as medical Systems Biology, signal transduction, computational biology, ecological control analysis, intracellular networks, hierarchical control analysis, Integrative bioinformatics, principles of Systems Biology, entering the living cell, Silicon Cell

    • obtain insight in the most important biological and biomedical issues, and in how they might be addressed scientifically

    • insight into what systems biology and integrative molecular biophysics may mean for society

    • unique and excellent profile for advanced interdisciplinary research between the physical sciences and the life sciences


    Top bmi sb curriculum structure 2 year 120 ects credit points l.jpg
    TOP-BMI/SB Systems Biology work for : Curriculum structure (2 year, 120 ECTS credit points)

    • Portal course 14 ECTS

    • 6 obligatory (5 ECTS) courses with each of the CRbCS professors 30 ECTS

    • 1 international experts’ lecture course 6 ECTS

    • orientation on future research project (including literature thesis) 12 ECTS

    • refereeing of research proposal 3 ECTS

    • 8 months research project in Amsterdam and foreign laboratory 40 ECTS

    • scientific article about research project 5 ECTS

    • following and discussing, reporting on scientific seminars 2 ECTS

    • scientific conference (co-organizing, participating, reporting) 3 ECTS

    • preparation for final comprehensive exam 5 ECTS


    Top bmi sb obligatory courses l.jpg
    TOP-BMI/SB Systems Biology work for Obligatory courses:

    • Portal course: entry course of mathematics and physics for the biologist and biology for the physics/chemistry/mathematics bachelor

    • Biomolecular dynamics (Van Grondelle)

    • Single molecule biophysics and biochemistry (nanobiology) (Schmidt)

    • Chemistry of complex biomolecules (Van der Vies)

    • Looking at Integrating molecules (Lill)

    • Intracellular networks (Westerhoff)

    • Integrative bioinformatics (Heringa)

    • Current topics in biomolecular integration and systems biology (international lecturers, e.g. Heinrich)


    Top bmi sb l.jpg
    TOP-BMI/SB Systems Biology work for

    • Research projects:

    • One research exchange project in two laboratories (partly in Amsterdam and partly in one of the collaborating International Centers of Excellence), on Biomolecular Integration / Systems Biology


    Sb teaching to ph d students l.jpg
    SB teaching to Ph D students Systems Biology work for

    • Joint graduate school with Humboldt U (Berlin); Heinrich et al

    • Now extended with Goteborgh Yeast Center (Hohmann et al), EU funded

    • Many exchange projects already

    • Annual joint courses


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    SB teaching/human capital problems Systems Biology work for

    • Very difficult field because of combination top experiments and top theory

    • Lack of appreciation peer groups (Biologists look down upon physicists and mathematicians and vv)

    • Lack of society appreciation (insufficient job opportunities)

    • Insufficient interest young students in science


    The wtec visit to the netherlands the program58 l.jpg
    The WTEC visit to The Netherlands: Systems Biology work for 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......


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