Silvia Santos

Quantitative Cell Biology Laboratory

Control principles in cell decision making: lessons from quantitative biology

During cell decision-making, gene and protein networks dynamically change in response to cues in order to trigger different cellular states. How information is decoded and transmitted in order to commit to specific cell fates has been a fundamental question in cell and developmental biology. One way to understand this is to quantitatively monitor input-output relationships in single cells during decision-making. In this context, the quantitative cell biology lab aims to understand how signalling molecules are organized into circuits, how these circuits are spatio-temporally regulated and remodel in two important cellular decisions: cell division and cellular differentiation.

The decision to divide is a fundamental decision and the conserved networks that trigger cell division adapt and remodel in a variety of biological contexts including developmental transitions and malignancy. We have been exploring spatio-temporal control of cell division in mammalian cells and remodelling of cell cycle networks during developmental transitions, using embryonic stem cells as a model system.

Figure 1: Probing cell cycle dynamics in single cells using biosensors

Figure 1: Probing cell cycle dynamics in single cells using biosensors

Embryonic stem cells have the propensity to differentiate into the three germ layers. The switch between pluripotency and differentiation in these cells has been our paradigm of choice to understand how protein and gene networks decode cellular signals and thereby encode irreversible commitment to different cell fates.

Figure 2: Differentiating colony of human embryonic stem cells (hESC) expressing lineage specific biomarkers

Figure 2: Differentiating colony of human embryonic stem cells (hESC) expressing lineage specific biomarkers

Both lines of investigation are likely to have profound impact in the understanding of normal human development and the transition from healthy to disease states. We use quantitative approaches combining experimental methods (based on single cell live cell imaging, genomics, proteomics and chemical biology) with mathematical modelling. Multidisciplinary approaches have revolutionised the way we ask biological questions and have been crucial to uncover regulatory principles in cell decision-making.

Selected publications

Araujo AR, Gelens L, Sheriff R and Santos SDM (2016). Positive feedback keeps duration of mitosis temporally insulated from upstream cell cycle events. Molecular Cell 64, 362-375

Ochoa, D, Jonikas, M, Lawrence, RT, El Debs, B, Selkrig J, Typas, A, Vill J, Santos SDM, Beltrao, P (2016). An Atlas of Human Conditional Phospho-Regulation Mol Syst Biol 12(12):888

Johnson, JR*, Santos, SDM*, Johnson T, Pieper U, Strumillo M, Wagih O, Sali A, Krogan NJ, Beltrao P (2015). Prediction of Functionally Important Phospho-Regulatory Events in Xenopus laevis Oocytes. Plos Comp Biology 11(8):e1004362. doi: 10.1371

Santos, SDM*, Wollman, R, Meyer, T, Ferrell, J* (2012) Spatial positive feedback at the onset of mitosis. Cell 149, 1500-1513

Santos, SDM, and Ferrell, J (2008) Systems biology: On the cell cycle and its switches. Nature 454, 287-291

Santos, SDM, Verveer, P and Bastiaens, P (2007) Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate. Nature Cell Biology 9, 324-330 

Silvia Santos

Silvia Santos

  • 2008 PhD, EMBL-Heidelberg, Germany
  • 2009 Post-doctoral fellow, Stanford University, USA
  • 2014 Career Development Award (CDA), MRC-LMS, Imperial College London, London, UK
  • 2017 Group Leader, the Francis Crick Institute, London, UK