Principal Investigator, MBI
Assistant Professor, Mechanobiology Institute
Department of Biological Sciences, National University of Singapore
The lab focuses on the application of biophysics and live imaging to better understand how organisms reliably develop (i.e. how is development so robust?). We use Drosophila and fission yeast as model organisms to explore robustness in decision-making. We apply a broad approach to problems, combining live imaging, advanced image analysis and mathematical modeling.
Position can be defined by the use of spatially extended gradients of signaling molecules. Since biological processes are inherently noisy, these gradients require mechanisms to ensure that they are precisely interpreted. We examine how the mechanisms of gradient formation affect the robustness of the downstream signaling. We are also probing how morphogens can be reliably interpreted prior to obtaining their steady-state profile.
Temporal variations in development
A developing organism needs to regulate the onset of different process temporally as well as spatially. We explore temporal variability in different processes during development. We use lightsheet microscopy to examine single cells while also keeping a global view of the embryo. Such technology also has low photobleaching, allowing visualisation of development over many hours.
Even between closely related animals there can be considerable variation in body size. Yet, for example, organs are typically positioned in the correct relative position for each specimen. Using lightsheet microscopy, we explore Drosophila embryogenesis to examine when and how such scaling decisions are made.
TOOLS AND METHODS
We use state-of-the-art lightsheet microscopy. This enables us to image entire developing organisms in toto while also having sufficient spatial and temporal resolution to probe single cell behavior.
The lab produces large amounts of quantitative data. We develop sophisticated methodologies to handle terabytes of data and extract the biological relevant information.
Mathematical modeling is used to make predictions about system behavior. Methods used include reaction-diffusion equations and Gillespie stochastic simulations. We are also interested in exploring how gene regulatory networks ensure robust decision-making.
2010 – 2013 EIPOD Fellow in the groups of Dr Lars Hufnagel and Dr Eileen Furlong at EMBL-Heidelberg, Germany
2007 – 2010 Postdoctoral researcher in the group of Professor Martin Howard at John Innes Centre, Norwich, UK
2007 Ph.D. (Theoretical physics) University of Oxford
2004 M.Phys. 1st class, Cambridge University
2003 B.A. 1st class, Cambridge University
Anand P. Singh, Rémi Galland, Megan L. Finch-Edmondson, Gianluca Grenci, Jean-Baptiste Sibarita, Vincent Studer, Virgile Viasnoff. 3D Protein Dynamics in the Cell Nucleus. Biophysical Journal, Volume 112, Issue 1, p133–142, 10 January 2017. DOI: http://dx.doi.org/10.1016/j.bpj.2016.11.3196.
Nisha Bte Mohd Rafiq, Zi Zhao Lieu, Tingting Jiang, Cheng-han Yu, Paul Matsudaira, Gareth E. Jones, Alexander D. Bershadsky. Podosome Assembly is Controlled by the GTPase ARF1 and its Nucleotide Exchange Factor ARNO. The Journal of Cell Biology, January 2017. 216(1). 181-197. doi: 10.1083/jcb.201605104.
Jan W Krieger, Anand P Singh, Nirmalya Bag, Christoph S Garbe, Timothy E Saunders, Jörg Langowski & Thorsten Wohland. Imaging fluorescence (cross-) correlation spectroscopy in live cells and organisms. Nature Protocols 10, 1948–1974 (2015) doi:10.1038/nprot.2015.100. November 2015.
Matteo Rauzi, Uros Krzic, Timothy E. Saunders, Matej Krajnc, Primož Ziherl, Lars Hufnagel & Maria Leptin. Embryo-scale tissue mechanics during Drosophila gastrulation movements. Nature Communications 6, Article number: 8677 doi:10.1038/ncomms9677. October 2015.
Richards DM, Saunders TE. Spatiotemporal analysis of different mechanisms for interpreting morphogen gradients. Biophysical Journal. 2015. 108(8): 2061-2073.
K Pan, TE Saunders, IF Parra, M Howard and F Chang: Cortical regulation of cell size by a sizer cdr2p. eLife, (March 2014).
J Erceg, TE Saunders, C Giradout, Damien P Devos, L Hufnagel and EE Furlong: Subtle changes in motif positioning cause tissue-specific effects on robustness of enhancer activity. PLoS Genetics, e1004060 (January 2014).
Saunders TE. 2015. Aggregation-fragmentation model of robust concentration gradient formation. Physical Review E. 91. 022704. doi: 10.1103/PhysRevE.91.022704.
Krzic U, Gunther S, Saunders TE, Streichan SJ, Hufnagel L. 2012. Multiview light-sheet microscope for rapid in toto imaging. Nature Methods. 9(7). 730-733. doi: 10.1038/nmeth.2064.
Saunders TE, Pan KZ, Angel A, Guan Y, Shah JV, Howard M, Chang F. 2012. Noise reduction in the intracellular pom1p gradient by a dynamic clustering mechanism. Developmental Cell. 22(3). 558-572. doi: 10.1016/j.devcel.2012.01.001.
He F, Saunders TE, Wen Y, Cheung D, Jiao R, ten Wolde PR, Howard M, Ma J. 2010. Shaping a morphogen gradient for positional precision. Biophysical Journal. 99(3). 697-707. doi: 10.1016/j.bpj.2010.04.073.
Saunders TE, Howard M. 2009. When it pays to rush: interpreting morphogen gradients prior to steady-state. Physical Biology. 6(4). 046020. doi: 10.1088/1478-3975/6/4/046020.
Saunders TE, Howard M. 2009. Morphogen profiles can be optimized to buffer against noise. Physical Review E. 80(4 pt 1). 041902.