Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

Tel: +44 (0)1865 613200
Fax: +44 (0)1865 613201
Image showing the global movement of lipids in a model planar membrane
Matthieu Chavent, Sansom lab
Anaphase bridges in fission yeast cells
Whitby lab
Lactose permease represented using bending cylinders in Bendix software
Caroline Dahl, Sansom lab
Epithelial cells in C. elegans showing a seam cell that failed to undergo cytokinesis
Serena Ding, Woollard lab
Collage of Drosophila third instar larva optic lobe
Lu Yang, Davis lab
First year Biochemistry students at a practical class
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Béla Novák
Dynamics of cell cycle controls

Co-workers: Dr. Stefan Heldt, Lukas Hutter, Scott Rata, Michael Hopkins

The living cell is a dynamical system of molecular interactions. Most of the physiological characteristics of the cell (movement, growth, and division etc.) are emergent properties of underlying molecular networks rather than being determined by a single molecule. These molecular networks are intrinsically dynamic and they dictate both spatial and temporal behaviour of the cell. In order to understand the physiological consequences of these regulatory molecular networks we use computational methods. Our mathematical modelling focuses on the eukaryotic cell cycle control system, which is responsible for:

  1. Global and local temporal ordering of cell cycle events;

  2. blocking further cell cycle progression in response to checkpoint controls (activated by incomplete cell cycle events);

  3. adjusting the tempo of cell cycle progression to the growth rate of the cell (balanced growth and division).

Using nonlinear differential equations, we build computer models for cell cycle control network of budding and fission yeasts, frog and fruit fly embryos, and human cells. These models accurately reproduce the physiological properties of normal cell cycle progression as well as the bizarre properties of mutant cells that have been studied. Recently, we have developed a quantitative model of the temporal ordering of DNA replication and mitosis for the minimal Cdk control network of fission yeast (Fig. 1). The model also predicts phenotypes of novel mutants and unintuitive properties (bistability, hysteresis etc.) of the cell cycle machinery (see Fig. 2).

We also develop quantitative models for individual cell cycle transitions like (G1/S, G2/M, meta/anaphase and mitotic exit).

Our experimentalist collaborators provide valuable quantitative data in the following areas:
budding yeast cell cycle (Dr Frank Uhlmann, CRUK, LRI) and meiosis (Dr Wolfgang Zachariae, MPI, Martinsried), G1/S transition (Dr Chris Bakal, ICR, London), G2/M transition (Dr Helfrid Hochegger, U Sussex; Dr Sergio Moreno, Salamanca), Spindle Assembly Checkpoint (Dr Daniel Gerlich, IMBA, Vienna; Dr Ulrike Gruneberg, Dunn School, Oxford; Raquel Oliveira, Gulbenkian Inst, Lisbon) and mitotic exit (Prof Francis Barr, Biochemistry, Oxford).

Publications

1. Cundell, M.J., Bastos, R.N., Zhang, T., Holder, J., Gruneberg, U., Novák, B. & Barr, F.A. (2013): The BEG
    (PP2A-B55/ENSA/Greatwall) Pathway Ensures Cytokinesis follows Chromosome Separation. Molecular Cell 52:
    393-405.

2. Rattani, A., Vinod, P.K., Godwin, J., Tachibana-Konwalski, K., Wolna, M., Malumbres, M. Novák, B. & Nasmyth, K.     (2014): Dependency of the Spindle Assembly Checkpoint on Cdk1 Renders the Anaphase Transition Irreversible.
    Current Biology 24: 630-637.

3. Gérard, C., Tyson, J.J., Coudreuse, D. & Novák, B. (2015): Cell Cycle Control by a Minimal Cdk Network. PloS
    Computational Biology
11: e1004056. doi: 10.1371/journal.pcbi.1004056.

4. Hellmuth, S., Rata, S., Brown, A., Heidmann, S., Novák, B. & Stemmann, O. (2015): Human chromosome
    segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase pin1. Molecular Cell  58:
    495-506.

5. Mirkovic, M., Hutter, L.H., Novák, B. & Oliveira, R.A. (2015): Premature Sister Chromatid Separation Is Poorly
    Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback. Cell Report 13: 469-478.

6. Barr, A.R., Frank S. Heldt, F.S., Zhang, T., Bakal, C. & Novák, B. (2016): A Dynamical Framework for the All-or-
    None G1/S Transition.
Cell Systems 2: 27–37.

7. Chica, N., Rozalén, A.E., Pérez-Hidalgo, L., Rubio, A., Novák. B. &  Moreno, S. (2016): Nutritional Control of Cell
    Size by the Greatwall-Endosulfine-PP2A·B55 Pathway. Current Biology (in press)

More publications: PubMed | Researcher ID

Research Images

Fig. 1: The molecular mechanism of the minimal Cdk network driving the cell cycle of fission yeast.
 

Fig. 2: Projection of the cell cycle trajectory on a bifurcation diagram of the minimal Cdk network driving the cell cycle of fission yeast


Contact:bela.novak@bioch.ox.ac.uk
Graduate Student and Postdoctoral Positions: Enquiries with CV welcome
Website: www.sysbio.ox.ac.uk/people/staff-list/novakb