Bela Novak

Summary

Affiliation: University of Oxford
Country: UK

Publications

  1. pmc Dynamical modeling of syncytial mitotic cycles in Drosophila embryos
    Laurence Calzone
    Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Budapest, Gellért tér, Hungary
    Mol Syst Biol 3:131. 2007
  2. pmc A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins
    Tammy M K Cheng
    Biomolecular Modelling Laboratory, Cancer Research UK London Research Institute, London, United Kingdom
    PLoS Comput Biol 8:e1002738. 2012
  3. pmc PP2A/B55 and Fcp1 regulate Greatwall and Ensa dephosphorylation during mitotic exit
    Nadia Hegarat
    Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton, United Kingdom
    PLoS Genet 10:e1004004. 2014
  4. pmc Mathematical model for growth regulation of fission yeast Schizosaccharomyces pombe
    Luca Cerone
    School of Mathematical Sciences and Complex and Adaptive Systems Laboratory, University College Dublin, Dublin, Ireland
    PLoS ONE 7:e49675. 2012
  5. doi request reprint Systems-level feedback in cell-cycle control
    Bela Novak
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Biochem Soc Trans 38:1242-6. 2010
  6. pmc Design principles of biochemical oscillators
    Bela Novak
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Nat Rev Mol Cell Biol 9:981-91. 2008
  7. pmc Regulated protein kinases and phosphatases in cell cycle decisions
    Bela Novak
    Centre for Integrative Systems Biology and Department of Biochemistry, Oxford University, Oxford, UK
    Curr Opin Cell Biol 22:801-8. 2010
  8. ncbi request reprint Irreversible cell-cycle transitions are due to systems-level feedback
    Bela Novak
    Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
    Nat Cell Biol 9:724-8. 2007
  9. ncbi request reprint Rewiring the exit from mitosis
    Andrea Ciliberto
    Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Budapest, Hungary
    Cell Cycle 4:1107-12. 2005
  10. pmc Irreversibility of mitotic exit is the consequence of systems-level feedback
    Sandra López-Avilés
    Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nature 459:592-5. 2009

Collaborators

Detail Information

Publications38

  1. pmc Dynamical modeling of syncytial mitotic cycles in Drosophila embryos
    Laurence Calzone
    Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Budapest, Gellért tér, Hungary
    Mol Syst Biol 3:131. 2007
    ..The model can be used to predict the phenotypes of novel mutations and effective ranges of the unmeasured rate constants and transport coefficients in the proposed mechanism...
  2. pmc A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins
    Tammy M K Cheng
    Biomolecular Modelling Laboratory, Cancer Research UK London Research Institute, London, United Kingdom
    PLoS Comput Biol 8:e1002738. 2012
    ..Furthermore, we show that the systemic impact of missense mutations can be effectively quantified as a combination of protein stability change and pathway perturbation...
  3. pmc PP2A/B55 and Fcp1 regulate Greatwall and Ensa dephosphorylation during mitotic exit
    Nadia Hegarat
    Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton, United Kingdom
    PLoS Genet 10:e1004004. 2014
    ..Taken together our results suggest a hierarchy of phosphatases coordinating Greatwall, Ensa/ARPP19 and Cdk substrate dephosphorylation during mitotic exit. ..
  4. pmc Mathematical model for growth regulation of fission yeast Schizosaccharomyces pombe
    Luca Cerone
    School of Mathematical Sciences and Complex and Adaptive Systems Laboratory, University College Dublin, Dublin, Ireland
    PLoS ONE 7:e49675. 2012
    ..Finally we discuss extension of the model for describing mutant cells with more than two growth zones...
  5. doi request reprint Systems-level feedback in cell-cycle control
    Bela Novak
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Biochem Soc Trans 38:1242-6. 2010
    ..The checkpoint-controlled cell cycles are always driven by a negative-feedback loop amplified by double-negative feedbacks (antagonism)...
  6. pmc Design principles of biochemical oscillators
    Bela Novak
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Nat Rev Mol Cell Biol 9:981-91. 2008
    ..Positive feedback is one mechanism to delay the negative-feedback signal. Biological oscillators can be classified according to the topology of the positive- and negative-feedback loops in the underlying regulatory mechanism...
  7. pmc Regulated protein kinases and phosphatases in cell cycle decisions
    Bela Novak
    Centre for Integrative Systems Biology and Department of Biochemistry, Oxford University, Oxford, UK
    Curr Opin Cell Biol 22:801-8. 2010
    ..These general principles are applied to cell cycle transitions, with special emphasis on the roles of regulated phosphatases in orchestrating progression from one phase to the next of the DNA replication-division cycle...
  8. ncbi request reprint Irreversible cell-cycle transitions are due to systems-level feedback
    Bela Novak
    Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
    Nat Cell Biol 9:724-8. 2007
    ..This systems-level view of irreversibility is supported by many experimental observations...
  9. ncbi request reprint Rewiring the exit from mitosis
    Andrea Ciliberto
    Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Budapest, Hungary
    Cell Cycle 4:1107-12. 2005
    ..We show that the new wiring permits oscillations with a simpler and smaller network than previously envisaged and that the antagonism between MPF and Cdc20 suggests a new interpretation of the spindle checkpoint...
  10. pmc Irreversibility of mitotic exit is the consequence of systems-level feedback
    Sandra López-Avilés
    Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nature 459:592-5. 2009
    ..Our findings demonstrate that the unidirectionality of mitotic exit is not the consequence of proteolysis but of systems-level feedback required to maintain the cell cycle in a new stable state...
  11. pmc System-level feedbacks make the anaphase switch irreversible
    Enuo He
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom
    Proc Natl Acad Sci U S A 108:10016-21. 2011
    ..These and other puzzles associated with the mitotic checkpoint are addressed by a proposed molecular mechanism, which involves two positive feedback loops that create a bistable response of the checkpoint to chromosomal tension...
  12. pmc Computational modelling of mitotic exit in budding yeast: the role of separase and Cdc14 endocycles
    P K Vinod
    Department of Biochemistry, Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    J R Soc Interface 8:1128-41. 2011
    ..The model is also used for the systematic analysis of the recently discovered Cdc14 endocycles. The significance of Cdc14 endocycles in eukaryotic cell cycle control is discussed as well...
  13. doi request reprint The role of APC/C inhibitor Emi2/XErp1 in oscillatory dynamics of early embryonic cell cycles
    P K Vinod
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, UK
    Biophys Chem 177:1-6. 2013
    ..We show that Emi2 interferes with the intrinsic time-delay in APC/C activation and inactivation to increase the amplitude as well as shorten the period of Cyclin B oscillation...
  14. pmc The BEG (PP2A-B55/ENSA/Greatwall) pathway ensures cytokinesis follows chromosome separation
    Michael J Cundell
    University of Oxford, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK
    Mol Cell 52:393-405. 2013
    ..Therefore, temporal order during mitotic exit is promoted by the metazoan BEG pathway. ..
  15. pmc Switches and latches: a biochemical tug-of-war between the kinases and phosphatases that control mitosis
    Maria Rosa Domingo-Sananes
    Department of Biochemistry, Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Philos Trans R Soc Lond B Biol Sci 366:3584-94. 2011
    ..The bistable character of the switch implies the existence of a CycB threshold for entry into mitosis. The end of G2 phase is determined by the point where CycB level crosses the CycB threshold for Cdk1 activation...
  16. pmc Role for regulated phosphatase activity in generating mitotic oscillations in Xenopus cell-free extracts
    Tongli Zhang
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom
    Proc Natl Acad Sci U S A 110:20539-44. 2013
    ....
  17. ncbi request reprint Modeling the septation initiation network (SIN) in fission yeast cells
    Attila Csikasz-Nagy
    Materials Structure and Modeling Research Group of the Hungarian Academy of Sciences and Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, 1111, Budapest, Szt Gellert ter 4, Hungary
    Curr Genet 51:245-55. 2007
    ..The model predicts phenotypes of some uncharacterized mutant cells and shows how a cytokinesis checkpoint can stop the cell cycle if septation fails...
  18. pmc Cell cycle commitment in budding yeast emerges from the cooperation of multiple bistable switches
    Tongli Zhang
    Oxford Centre for Integrative Systems Biology OCISB, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Open Biol 1:110009. 2011
    ....
  19. ncbi request reprint Steady states and oscillations in the p53/Mdm2 network
    Andrea Ciliberto
    Molecular Network Dynamics Research Group of Hungarian Academy of Sciences, Budapest University of Technology and Economics, Budapest, Hungary
    Cell Cycle 4:488-93. 2005
    ..The model reproduces experimental data in quantitative detail. We suggest new experiments for dissecting the contributions of negative and positive feedbacks to the generation of oscillations...
  20. doi request reprint Interplay of transcriptional and proteolytic regulation in driving robust cell cycle progression
    Paula Freire
    Department of Biochemistry, University of Oxford, Oxford, UK
    Mol Biosyst 8:863-70. 2012
    ..We show that both regulated transcription and degradation are part of feedback loops in the network which ensure robust function against parametric variations that can arise from the mutations and/or variations in protein levels...
  21. pmc Molecular mechanisms creating bistable switches at cell cycle transitions
    Anael Verdugo
    Department of Biochemistry, University of Oxford, Oxford, UK
    Open Biol 3:120179. 2013
    ..Variations of the motif might support irreversible cellular decision-making in other contexts...
  22. doi request reprint Meiotic prophase requires proteolysis of M phase regulators mediated by the meiosis-specific APC/CAma1
    Elwy Okaz
    Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
    Cell 151:603-18. 2012
    ..Thus, control of prophase I by meiotic mechanisms depends on the suppression of the alternative, mitotic mechanisms by a meiosis-specific form of the APC/C...
  23. pmc System-level feedbacks control cell cycle progression
    Orsolya Kapuy
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, UK
    FEBS Lett 583:3992-8. 2009
    ..We have also argued that bistability underlies irreversible transitions between low and high Cdk activity states and thereby ensures directionality of cell cycle progression...
  24. ncbi request reprint A model for restriction point control of the mammalian cell cycle
    Bela Novak
    Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Gellert ter 4, 1521 Budapest, Hungary
    J Theor Biol 230:563-79. 2004
    ....
  25. ncbi request reprint Reverse engineering models of cell cycle regulation
    Attila Csikasz-Nagy
    Materials Structure and Modeling Research Group of the Hungarian Academy of Sciences, Budapest, Hungary
    Adv Exp Med Biol 641:88-97. 2008
    ....
  26. pmc Dynamical scenarios for chromosome bi-orientation
    Tongli Zhang
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Biophys J 104:2595-606. 2013
    ..Based on our results and supported by experimental data, we put forward a trial-and-error oscillation and a stochastic bistable switch as two elegant mechanisms with the potential to promote bi-orientation both efficiently and robustly. ..
  27. doi request reprint Different effects of redundant feedback loops on a bistable switch
    Maria Rosa Domingo-Sananes
    Department of Biochemistry, Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom
    Chaos 20:045120. 2010
    ..We speculate that this conclusion could be general for other bistable systems with redundant feedback loops...
  28. pmc Minimal models for cell-cycle control based on competitive inhibition and multisite phosphorylations of Cdk substrates
    Claude Gérard
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Biophys J 104:1367-79. 2013
    ....
  29. pmc Bistability by multiple phosphorylation of regulatory proteins
    Orsolya Kapuy
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Prog Biophys Mol Biol 100:47-56. 2009
    ....
  30. ncbi request reprint Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast
    Ethel Queralt
    Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Cell 125:719-32. 2006
    ..These findings allow us to present a new quantitative model for mitotic exit in budding yeast...
  31. doi request reprint Regulation of APC/C activity in oocytes by a Bub1-dependent spindle assembly checkpoint
    Barry E McGuinness
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom
    Curr Biol 19:369-80. 2009
    ..Experimental approaches hitherto used to inactivate the SAC in oocytes suffer from a number of drawbacks...
  32. ncbi request reprint Microtubules offset growth site from the cell centre in fission yeast
    Stefania Castagnetti
    Cancer Research UK, Cell Cycle Lab, London, WC2A 3PX, UK
    J Cell Sci 120:2205-13. 2007
    ..The principle of this symmetry-breaking design may also apply to the morphogenesis of other cells...
  33. pmc Dependency of the spindle assembly checkpoint on Cdk1 renders the anaphase transition irreversible
    Ahmed Rattani
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Curr Biol 24:630-7. 2014
    ..The mutual activation of tension sensitive SAC and Cdk1 creates a bistable system that ensures complete activation of separase and total downregulation of Cdk1 when all chromosomes have bioriented. ..
  34. pmc A model for the epigenetic switch linking inflammation to cell transformation: deterministic and stochastic approaches
    Claude Gérard
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom de Duve Institute, Universite Catholique de Louvain UCL, Brussels, Belgium
    PLoS Comput Biol 10:e1003455. 2014
    ..Depending on their microRNA targets, the model predicts that ceRNAs could act as oncogenes or tumor suppressors by regulating the occurrence of cell transformation. ..
  35. pmc microRNA as a Potential Vector for the Propagation of Robustness in Protein Expression and Oscillatory Dynamics within a ceRNA Network
    Claude Gérard
    Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    PLoS ONE 8:e83372. 2013
    ..Thus, by means of computational models, we show that miRNAs could act as vectors allowing the propagation of robustness in protein synthesis as well as oscillatory behaviors within ceRNA networks. ..
  36. pmc Hypoxia-dependent sequestration of an oxygen sensor by a widespread structural motif can shape the hypoxic response--a predictive kinetic model
    Bernhard Schmierer
    Oxford Centre for Integrative Systems Biology OCISB, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    BMC Syst Biol 4:139. 2010
    ..Competition by ARD proteins for FIH is hypothesised to affect FIH activity towards HIFα; however the extent of this competition and its effect on the HIF-dependent hypoxic response are unknown...