“Multidisciplinary approaches are crucial to understanding spatio-temporal control principles in cell decision-making.”
During cell decision-making, signal transduction networks dynamically change in time and space in response to cues and thereby trigger different cellular states. The challenge we face as researchers is to be able to predict what happens to intracellular signalling when the microenvironment of a cell changes. The quantitative cell biology lab aims to monitor how signalling molecules are organized into circuits, how these circuits are spatio-temporally regulated and how they remodel during transitions.
Our lab is therefore interested in understanding intracellular strategies (or control principles) when cells adapt to different biological contexts. Our lab is particularly interested in understanding how the biochemical machinery that drives cell division self-organises in different cellular contexts. We plan to investigate how positive feedback control and spatial gradients of activities regulate the precise timing and ordering of events during cell division, and explore how the cell cycle machinery remodels during the embryonic to somatic transition. We use multidisciplinary approaches combining quantitative experimental methods (live cell imaging, molecular biology, biochemistry and chemical biology) with mathematical modelling and computation. The combination of experiments and theory is crucial to uncover general control principles in cell decision-making.
Opportunities at the Quantitative Cell Biology group:
We are looking for highly motivated researchers who enjoy working in a multi-disciplinary and collaborative environment to join our group! For more info please contact Dr Silvia Santos for formal inquiries.
Figure 1: (a-d) Monitoring activation profiles and cell division events in single human somatic cells using biosensors.
Figure 2: Some of the quantitative approaches used in the lab: (a) live cell imaging, (b) mass spectrometry, (c) pharmacological/genetic/chemical screening, (d) computational analysis, (e) mathematical modelling a (f) network reconstruction.
Ochoa, D, Jonikas, M, Lawrence, RT, El Debs, B, Selkrig, J, Typas, A, Ville, J, Santos, SDM and Beltrao, P (2016) An Atlas of Human Kinase Regulation. Mol Syst Biology 12 (12)
Araujo, AR, Gelens, L, Sheriff RS, Santos, SDM (2016) Positive Feedback Keeps Duration of Mitosis Temporally Insulated from Upstream Cell-Cycle Events. Mol Cell. 64(2):362-375
Ochoa, D, Jonikas, M, Lawrence, RT, El Debs, B, Selkrig, J, Typas, A, Ville, J, Santos, SDM and Beltrao, P (2016) An Atlas of Human Kinase Regulation. Mol Syst Biology (in press)
Johnson JR, Santos SD, 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 Comput Biol. 11(8):e1004362. doi: 10.1371/journal.pcbi.1004362.
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