Welcome to the
Saunders lab

How does complex organ shape emerge during development? How is organ formation coordinated to ensure robust morphogenesis? We use quantitative biology techniques and modelling to help answer these important questions. We are particularly interested in how mechanical interactions guide morphogenesis, and how such mechanics interact with signalling networks during development.

Latest news: PhD positions for 2022 are beginning to be advertised. The first are now available to apply: MIBTP

About Us

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Timothy Saunders

Associate Professor

Mario Mendieta

Post-Doctoral Research Fellow

Rachna Narayanan

Post-Doctoral Research Fellow

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Thamarailingam Athilingam

Post-Doctoral Research Fellow

Bernardo Chapa Y Lazo

Post-Doctoral Research Fellow

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Tricia Loo

Graduate Student

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Pearlyn Toh

Graduate Student

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Sunandan Dhar

Graduate Student

Serena Thomas

Graduate Student

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Veena Venugopal

Research Assistant (Singapore Lab)

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Prachi Deshchougule

Research Associate (Warwick Lab)

Research Areas

My lab studies how complex three-dimensional tissue shape emerges during embryo development. We utilise high spatiotemporal resolution imaging combined with advanced genetic and biophysical techniques to record organ formation at unprecedented detail.
We use two main model systems in the lab: the formation of vertebrate muscle (Zebrafish); and heart morphogenesis (Drosophila (fruit fly)). These systems offer us the imaging capabilities and genetic tractability required to make meaningful insights into how these organs form.

The Emergence of Complex Organ Shape

We have generated four-dimensional maps of the developing zebrafish skeletal muscle (myotome). The myotome has signalling inputs from three orthogonal morphogens (BMP, Shh, FGF), as well as considerable cellular rearrangements and cell shape changes. Using our maps, we have uncovered non-autonomous modes of FGF action in regulating cell fate specification by Shh. Further, we have revealed how the distinctive chevron shape of the myotome emerges in zebrafish. This may well be a common strategy in swimming vertebrates that show similar shapes.

Building Complex Internal Organ Structure

We have explored the role of differential mechanical interactions in the formation of the Drosophila heart. In particular, we have focused on the question of how cells of the same type reliably match during cardiogenesis. We have found that cell adhesion molecules Fasciclin-III and Teneurin-m act complementarily to provide an adhesion gradient across each heart segment, which results in reliable cell matching. By ensuring that the right cells become adhered, such mechanical proofreading is able to ensure that the heart forms properly.

Three-Dimensional Tissue Morphogenesis

Developing organisms are three-dimensional, yet much research into tissue mechanics and interactions has focused on relatively flat tissues due to accessibility. We are exploring how cells arrange and compete for space in curved three-dimensional environments. Using theory and experiment, we have shown that during cellularisation in the Drosophila embryo, cells undergo skew and apical-to-basal neighbour rearrangements to adapt for geometric constraints.

Organ Scaling

Every human is a different shape and size. Yet, in the vast majority of us, our organs are the right size for our body and positioned in the same relative location. Such scaling begins early in the embryo development. Yet, the mechanisms underlying scaling are poorly understood. We are using Drosophila and Zebrafish to explore how organs adapt to size changes. We have taken advantage of genetically induced smaller embryos in Drosophila to bring new insights into when and where organ scaling occurs in the embryo. On the one hand, the developing heart scales precisely with embryo length, yet the developing central nervous system has a more absolute length. We are currently looking to understand how such organ size adaptation occurs.

Web Presence

Mechanobiology Institute, National University of Singapore
Centre for Mechanochemical Biology, University of Warwick
Warwick Medical School, University of Warwick
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Publons

Recent Articles on Our Work

Nature article on the role of forces in development, which highlights our recent work on Myosin II waves in heart formation.

Podcast with Richard Jacobs on how internal organs form during development.

Prelights article on our paper about scaling in the early Drosophila embryo.


Publications

Developmental Biology

Preprints

Lai JKH, Toh PJY, Cognart HA, Chouhan G and Saunders TE. DNA-damage induced cell death in yap1; wwtr1 mutant epidermal basal cells. Biorχiv

Karkali K, Saunders TE, Vernon SW, Baines RA, Panayotou G, Martín-Blanco E. JNK signaling in pioneer neurons directs the architectural organization of the CNS and coordinates the motor activity of the Drosophila embryo. Biorχiv

Amourda C, Chong J and Saunders TE. MicroRNAs buffer genetic variation at specific temperatures during embryonic development. Biorχiv

2021

Review: Saunders TE. The early Drosophila embryo as a model system for quantitative biology. Cells and Development 2021;:203722. [PMID: 34298230] Link

Yadav V, Tolwinski N, and Saunders TE. Spatiotemporal sensitivity of mesoderm specification to FGFR signalling in the Drosophila embryo. Scientific Reports 2021; 11(1):14091. [PMID: 34238963] Link

2020

Review: Mirth CK, Saunders TE, and Amourda C. Growing Up in a Changing World: Environmental Regulation of Development in Insects. Annual Reviews Entomology 2020;. [PMID: 32822557] Link

Bosze B, Ono Y, Mattes B, Sinner C, Gourain V, Thumberger T, Tlili S, Wittbrodt J, Saunders TE, Strähle U, Schug A and Scholpp S. Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish. Histochemistry and Cell Biology 2020; 154: 463. Link

Huang A, Rupprecht JF and Saunders TE. Embryonic geometry underlies phenotypic variation in decanalized conditions. eLife 2020: 9; e47380. [PMID: 32048988]. Link

Amourda C and Saunders TE. The mirtron miR-1010 functions in concert with its host gene SKIP to balance elevation of nAcRβ2. Scientific Reports 2020; 10:1. [PMID 32015391]. Link

Review: Huang A and Saunders TE. A matter of time: Formation and interpretation of the Bicoid morphogen gradient. Current Topics in Developmental Biology 2020; 137: 79. [PMID: 32143754] Link

2019

Commentary: Saunders TE and Ingham PW. Open questions: how to get developmental biology into shape? BMC Biology 2019; 17:1. [PMID: 30795745] Link

2018

Yin J, Lee R, Ono Y, Ingham PW and Saunders TE. Spatiotemporal coordination of FGF and Shh signaling underlies the specification of myoblasts in the zebrafish embryo. Developmental Cell 2018; 46; 73 [PMID: 30253169] Link

Durrieu, L Kirrmaier D, Schneidt T, Kats I, Raghavan S, Hufnagel L, Saunders TE and Knop M. Bicoid gradient formation mechanism and dynamics revealed by protein lifetime analysis. Molecular Systems Biology 2018; 14: e8355 [PMID: 30181144] Link

Chong J, Amourda C and Saunders TE. Temporal development of Drosophila embryos is highly robust across a wide temperature range. Journal of the Royal Society Interface 2018; 15: 20180304. [PMID: 29997261] Link

2017

Huang A, Amourda C, Zhang S, Tolwinski NS and Saunders TE. Decoding temporal interpretation of the morphogen Bicoid in the early Drosophila embryo. eLife 2017; 6: e26258. [PMID: 28691901] Link

Review: Amourda C and Saunders TE. Gene expression boundary scaling and organ size regulation in the Drosophila embryo. Development, Growth and Differentiation 2017; 59: 21. [PMID: 28093727] Link

2014

Pan KZ, Saunders TE, Flor-Parra I, Howard M and Chang F. Cortical regulation of cell size by a sizer cdr2p. eLife 2014; 3: e02040. [PMID:24642412] Link

Erceg J, Saunders TE, Girardot C, Devos DP, Hufnagel L and Furlong EEM. Subtle changes in motif positioning cause tissue-specific effects on robustness of an enhancer's activity. PLoS Genetics 2014; 10: e1004060. [PMID: 24391522] Link

2012

Saunders TE, Pan KZ, Angel A, Guan Y, Shah JV, Howard M and Chang F. Noise reduction in the intracellular pom1p gradient by a dynamic clustering mechanism. Developmental Cell 2012; 22: 558. [PMID: 22342545] Link

2010

He F, Saunders TE, Wen Y, Cheung D, Jiao R, ten Wolde PR, Howard M and Ma J. Shaping a morphogen gradient for positional precision. Biophysical Journal 2010; 99: 69. [PMID: 20682246] Link

Mechanobiology

Preprints

Toh PJY, Lai JKH, Hermann A, Destaing O, Sheets MP, Sudol M and Saunders TE. Optogenetic manipulation of YAP cellular localisation and function. Biorχiv

de-Carvalho J, Tlili S, Hufnagel L, Saunders TE and Telley IA. Aster repulsion drives local ordering in an active system. Biorχiv

Karkali K, Tiwari P, Singh A, Tlili S, Jorba I, Navajas D, Muñoz JJ, Saunders TE and Martin-Blanco E. Condensation of the Drosophila Nerve Cord is Oscillatory and depends on Coordinated Mechanical Interactions. Biorχiv

Yin J and Saunders TE. Shh induces symmetry breaking in the presomitic mesoderm by inducing tissue shear and orientated cell rearrangements Biorχiv

2021

Tiwari P, Rengarajan H, and Saunders TE. Scaling of Internal Organs during Drosophila Embryonic Development. Biophysical Journal 2021; 120: 1-13. [PMID: 34087212] Link

Review: Narayanan R, Mendieta-Serrano MA, and Saunders TE. The role of cellular active stresses in shaping the zebrafish body axis. Current Opinion in Cell Biology 2021; 73:69-77. [PMID: 34303916] Link

Review: Athilingam T, Tiwari P, Toyama Y, and Saunders TE. Mechanics of epidermal morphogenesis in the Drosophila pupa. Seminars in Cell and Developmental Biology 2021; [PMID: 34167884] Link

Review: Zhang S and Saunders TE. Mechanical processes underlying precise and robust cell matching. Seminars in Cell and Developmental Biology. Link

Commentary: Lenne PF el al. Roadmap on multiscale coupling of biochemical and mechanical signals during development. Physical Biology 2020;. [PMID: 33276350] Link

2020

Colin L, Chevallier A, Tsugawa S, Gacon F, Godin C, Viasnoff V, Saunders TE, and Hamant O. Cortical tension overrides geometrical cues to orient microtubules in confined protoplasts. PNAS 2020;. [PMID: 33288703] Link

Zhang S, Teng X, Toyama Y, and Saunders TE. Periodic Oscillations of Myosin-II Mechanically Proofread Cell-Cell Connections to Ensure Robust Formation of the Cardiac Vessel. Current Biology 2020; 30: 3364. [PMID: 32679105] Link

Review: Hamant O, and Saunders TE. Shaping Organs: Shared Structural Principles Across Kingdoms. Annual Reviews Cell and Developmental Biology 2020;. [PMID: 32628862] Link

2019

Tlili S, Yin J, Rupprecht J-F, Mendieta-Serrano MA, Weissbart G, Verma N, Teng X, Toyama Y, Prost J and Saunders TE. Shaping the zebrafish myotome by intertissue friction and active stress. PNAS 2019; 116: 25430. [PMID: 31772022] Link

2018

Zhang S, Amourda C, Garfield D and Saunders TE. Selective filopodia adhesion ensures robust cell matching in the Drosophila heart. Developmental Cell 2018; 46: 189. [PMID: 30016621] Link

2017

Sun Z, Amourda C, Shagirov M, Hara Y, Saunders TE and Toyama Y. Basolateral protrusion and apical contraction cooperatively drive Drosophila germ-band extension. Nature Cell Biology 2017; 19:375. [PMID: 28346438] Link

Review: Saunders TE. Imag(in)ing growth and form. Mechanisms of Development 2017; 145: 13. [PMID: 28351699] Link

2015

Rauzi M, Krzic U, Saunders TE, Krajnc M, Ziherl P, Hufnagel L and Leptin M. Embryo-scale tissue mechanics during Drosophila gastrulation movements. Nature Communications 2015; 6: 1-12. [PMID: 26497898] Link

Theory and Imaging

Preprints

Tlili S, Shagirov M, Zhang S and Saunders TE. Interfacial energy constraints are sufficient to align cells over large distances. Biorχiv

2020

Thamm A, Saunders TE and Dolan L. MpFEW RHIZOIDS1 miRNA-mediated lateral inhibition controls rhizoid cell patterning in Marchantia polymorpha. Current Biology 2020; 30: 1905. [PMID: 32243863] Link

Bezeljak U, Loya H, Kaczmarek B, Saunders TE, Loose M. Stochastic activation and bistability in a Rab GTPase regulatory network. PNAS 2020; 117: 6540. [PMID: 32161136] Link

2019

Connahs H, Tlili S, van Creij J, Loo TYJ, Banerjee TD, Saunders TE and Monteiro A. Activation of butterfly eyespots by Distal-less is consistent with a reaction-diffusion process. Development 2019; 146: dev169367 [PMID: 30992277] Link

2017

Kaur P, Saunders TE and Tolwinski NS. Coupling optogenetics and light-sheet microscopy, a method to study Wnt signaling during embryogenesis. Scientific Reports 2017; 7: 1-11. [PMID: 29192250] Link

Singh AP, Galland R, Finch-Edmondson ML, Grenci G, Sibarita J-B, Studer V, Viasnoff V and Saunders TE. 3D protein dynamics in the cell nucleus. Biophysical Journal (2017); 112: 133. [PMID: 28076804] Link

2015

Krieger JW, Singh AP, Bag N, Garbe CS, Saunders TE, Langowski J and Wohland T. Imaging fluorescence (cross-) correlation spectroscopy in live cells and organisms. Nature Protocols 2015; 10: 1948. [PMID: 26540588] Link

Richards DM and Saunders TE. Spatiotemporal analysis of different mechanisms for interpreting morphogen gradients. Biophysical Journal 2015; 108: 2061-2073. [PMID: 25902445] Link

Saunders TE. Aggregation-fragmentation model of robust concentration gradient formation. Physical Review E 2015; 91: 022704. [PMID: 25768528] Link

2012

Krzic U, Gunther S, Saunders TE, Streichan SJ and Hufnagel L. Multiview light-sheet microscope for rapid in toto imaging. Nature Methods 2012; 9: 730. [PMID: 22660739] Link

2010

Andreanov A, Chalker JT, Saunders TE and Sherrington D. Spin-glass transition in geometrically frustrated antiferromagnets with weak disorder. Physical Review B 2010; 81: 014406 Link

2009

Saunders TE and Howard M. When it pays to rush: interpreting morphogen gradients prior to steady-state. Physical Biology 2009; 6: 046020. [PMID: 19940351] Link

Saunders TE and Howard M. Morphogen profiles can be optimized to buffer against noise. Physical Review E 2009; 80: 041902. [PMID: 19905337] Link

2008

Pickles T, Saunders TE and Chalker JT. Critical phenomena in a highly constrained classical spin system: Néel ordering from the Coulomb phase. Europhysics Letters 2008; 84: 36002 Link

Saunders TE and Chalker JT. Structural phase transitions in geometrically frustrated antiferromagnets. Physical Review B 2008; 77: 214438 Link

2007

Saunders TE and Chalker JT. Spin freezing in geometrically frustrated antiferromagnets with weak disorder. Physical Review Letters 2007; 98: 157201 Link

Editorial and Refereeing Duties

I am on the editorial board for Cells and Development.
I am currently editing a special issue for Seminars in Cell and Developmental Biology. Previously, I have edited a special issue for Mechanisms of Development (now Cells and Development) with Prof. Philip Ingham on 100 years since "On Growth and Form" by D'Arcy Wentworth-Thompson: Link
I have been an invited handling editor for eLife.
I have reviewed for a large range of journals, including: Nature, Nature Cell Biology, Current Biology, PNAS, Development, Developmental Cell, PLoS Biology, PLoS Computational Biology, Molecular Systems Biology, Physical Review Letters, Physical Review E, Cells and Development, Molecular Biology of the Cell, EMBO, Cell Systems, Cell Reports.
I have reviewed for a broad range of international grant agencies, including: BBSRC (UK), Wellcome (UK), DFG (Germany), ERC (EU) and Agence Nationale de la Recherche (France).

Outreach

The Saunders lab has been involved in a range of outreach activities. We have had school student researchers join the lab for an internship. Timothy Saunders has given talks to schools and the Science Cafe. If you're interested to know more, please contact us. We also have a number of related publications, outlined below.

Policy


Hamant O, Saunders TE and Viasnoff V. Seven steps to make travel to scientific conferences more sustainable. Nature 2019; 573: 7774 Link

Baur G, Fakhri N, Kicheva A, Kondev J, Kruse K, Noji H, Riveline D, Saunders TE, Thatta M and Wieschaus E. The science of living matter for tomorrow. Cell Systems 2018; 6: 400. Link

Education


Saunders TE, He CY, Koehl P, Ong SLL and So PTC. Eleven quick tips for running an interdisciplinary short course for new graduate students. PLoS Computational Biology 2018; 14: e1006039. Link

Saunders TE. The physics of crowds. Science in Schools 2011. Link

Outreach


Singh AP, Gupta A, Gulvady R, Mhamane A and Saunders TE. Doing is understanding: science fun in India. Science in Schools 2015. Link

Job Opportunities

Graduate
Students


The lab has a strong record in students submitting high quality theses on time. Past students have gone onto post-doctoral and industrial positions.

At University of Warwick there are numerous potential routes for starting a PhD in the lab. Importantly, all these programs stress interdisciplinarity, which lies at the heart of the lab's approach to science.

For wet-lab orientated people, there are:

Medical Research Council Doctoral Training Program

Midlands Integrative Biosciences Training Partnership. See also MIBTP Saunders webpage For 2022, there is a project now available to apply for.

For dry-lab orientated people, there are:

EPSRC Centre for Doctoral Training in Modelling of Heterogeneous Systems - HetSys

Mathematics for Real-World Systems Centre for Doctoral Training - MathSys

For Chinese students, University of Warwick has a dedicated PhD program: link. I have a strong record in supporting Chinese students to complete high quality PhD studies.

Post-Doctoral Researchers


I welcome interested PhD holders to contact me about potential opportunities in the lab. I am generally interested in both developmental biologists and experimental and theoretical biophysicists, but I am open to engaged researchers from other backgrounds.

There are opportunities with international and national agencies for independent positions, particularly with regards to programs encouraging interdisciplinarity, including:

The EUTOPIA post-doctoral felloship scheme. This is an exciting opportunity to develop a collaboration between University of Warwick and other select institutions across Europe. Please contact me if you're interested in applying with my lab. Further details here.

HFSP

EMBO

Leverhulme Trust

Wellcome

Undergraduate and others


I welcome interested undergraduate and masters students to contact me with regards to opportunities in the lab. For University of Warwick students, I am open to taking students for both third year projects and fourth year extended lab experience.

I have also had school pupils in the lab. I am open to giving a research experience for pre-University people, but there may be limitations.

Lab Alumni

Graduate
Students


Anqi Huang (2013-2018); currently post-doc in the Vincent lab at the Crick Institute, London, UK.

Jianmin Yin (2013-2018); currently post-doc in the Affolter lab at the Biozentrum, Basel, Switzerland.

Shaobo Zhang (2014-2020); currently post-doc in the Xin Duan lab at UCSF, San Francisco, USA.

Vaishali Yadav (2016-2021); Research Analyst at Costello Medical, Cambridge, UK.

Post-doctoral
Researchers


Dr. Christopher Amourda (2014-2019); currently post-doc in the Miguel-Aliaga lab at Imperial College, London, UK.

Dr. Anand Singh (2014-2017); currently post-doc in the Gregor lab at Princeton, USA.

Dr. Sham Tlili (2015-2019); currently holds a CNRS position in the Lenne lab at IBDM, Marseilles, France.

Dr. Prabhat Tiwari (2017-2022); currently post-doc in the Bach lab , NYU Langone Medical Center, New York, USA

Dr. Jason Lai (2018-2021); currently at Hummingbird Biosciences, Singapore.

Research Assistants
and Undergrads


I have had three Research Assistants and over 15 undergraduate researchers in my lab since 2014. Some examples are below:

Boon Heng Ng (2020-2021); currently PhD student in the Chan lab at the Mechanobiology Institute, Singapore.

Catriona Breen (2019); currently PhD student in the Srivastava lab at Harvard, Cambridge, USA.

Hrushiken Loya (2018); currently PhD student in the Wellcome Centre Human Genetics, University of Oxford, UK

Kushal Joshi (2018); currently PhD student in the Keenan Research Centre for Biomedical Science , Toronto, Canada.

Jeronica Chong (2014-2017); currently PhD student in the Phng lab at RIKEN, Kobe, Japan.

Contact Us

Saunders Laboratory
Level 3, Interdisciplinary Biomedical Research Building
Warwick Medical School
Gibbet Hill Road, CV4 7AL
Coventry
UNITED KINGDOM

Telephone: +44 (0) 2476 523095