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Dr Michael Smutny

Supervisor Details

Michael Smutny

Contact Details

Dr Michael Smutny

Warwick Medical School, University of Warwick

Research Interests

Our research is focused on the crosstalk between cell and tissue-scale mechanics and biochemical signaling to regulate developmental programs and cellular mechanisms in the embryo, including cell/tissue morphogenesis and polarization, cell-cell adhesion, cell migration, cell fate specification and tissue patterning events. To answer these questions, we are using quantitative live cell imaging, biophysical force measurements, biochemical and genetic tools, genomics/transcriptomics and mathematical modeling from subcellular, to tissue level. We are utilizing the zebrafish embryo as a vertebrate model system to study these questions due to transparency and rapid development ex utero, facilitating in vivo live cell imaging, chemical and mechanical perturbations and cell/tissue isolation for in vitro assays.

The current research focus is on two main events during zebrafish gastrulation: the first process comprises the early development of the prospective anterior neural plate (ANP), where neural precursor cells (neurectoderm) become positioned and specified along the embryonic axes into specific domains to contribute to the formation of the central nervous system (CNS). We are interested in unraveling the role of mechanical forces in neurectoderm cell/tissue morphogenesis, movement and cell specification/tissue patterning to develop a functional CNS. The second event involves the coordinated movements of internalized mesendoderm (prechordal plate) cells, which migrate as a cell collective towards the animal pole of the embryo and contribute to embryonic axes formation. We are investigating the role of physical forces and the external microenvironment for cell polarization, migration, adhesion and cell specification.

Scientific Inspiration

Nature. Shows us that we still do not understand much and we should keep asking questions.

Project Details

Dr Smutny is the supervisor on the below project:

Understanding early tissue formation in the embryo and outside mimicking developmental programmes

Secondary Supervisor(s): Professor Andrew McAinsh

University of Registration: University of Warwick

BBSRC Research Themes: Understanding the Rules of Life (Stem Cells)

Apply here!

Deadline: 23 May, 2024

Project Outline

Background and scientific rationale

Embryonic tissues and organs are shaped and patterned by complex genetic, molecular and cellular mechanisms that regulate essential processes during development [1]. Dissecting such mechanisms remains challenging as the formation of tissues is controlled on different levels including genes that regulate cell-fate decisions, biochemical signalling pathways and mechanical (physical) forces that act within and between cells to define 3D form and function. Our group aims to understand how these complex processes on multiple scales are linked using the zebrafish embryo as a model system – from tissue to cells, from the cell membrane to the nucleus, and on transcriptional/genomic level. This requires an interdisciplinary approach where we combine approaches from molecular and cell biology, state-of-the-art microscopy, organoids, biophysics tools, computational image analysis, transcriptomics and theoretical modelling.

In particular, the lab is interested in processes during development such as cell movements, cell divisions, cell shape changes, cell adhesion and cell fate specification that require feedback between biochemical and mechanical signals [2]. It is now well recognised that cells for example push and pull on each other and thereby triggering profound changes in cell and tissue behaviour that are essential to drive many developmental programmes [1]. However, the precise molecular and cellular mechanisms involved are not well explored. We aim to gain mechanistic insights into how tissues get their shape, how cells migrate directionally, how cells communicate via cell-cell adhesions and how cells change their identity or state.

Below are examples of potential projects available that highlight the broad scope of topics and technologies the lab:

1 - Feedback between cell fate specification and tissue morphogenesis

This project investigates how progenitor cells organise into different territories and establish sharp boundaries during tissue formation in the early embryo [3].


Unravelling how cellular and tissue dynamics contribute to establishing different territories in the early brain with distinct cell fates.


Live imaging and immunofluorescence of zebrafish embryos, quantitative image analysis of cellular morphodynamics (movement, shape) and molecules involved in cell fate specification (transcription factors, morphogens). Biophysical characterisation of isolated cells in vivo and ex vivo.

2 - Cellular force sensing and response

Cells can sense mechanical stimuli from the microenvironment. [4]. Yet, it is still unclear how embryonic stem (ES) cells respond to specific forces to activate specific cell and developmental programmes


Identifying how ES cells sense and respond to mechanical signals and regulate essential processes including cell division or cell fate specification.


Live cell imaging and immunofluorescence of cells in the embryo and isolated cells ex vivo, cell confiner, atomic force microscopy (AFM), computational image analysis of cell and molecule dynamics. Characterisation of nuclear mechanics and response.

3 - Self-organisation of early brain development

Recent stem cell models (gastruloids, organoids) highlight the remarkable potential to recapitulate early embryonic development through self-organisation and patterning in vitro [5].


Establishing cell culture conditions mirroring early embryonic brain development and investigating the role of biomechanics in cell fate patterning.


Generation of ES cell-derived aggregates in tissue culture. Live imaging and immunofluorescence (confocal, multiphoton), micropatterning, chemical and physical perturbations, computational image analyses of cell morphodynamics (movements, shapes) and tissue patterning.


  1. Gilmour D. et al. Nature. 2017
  2. Heisenberg CP. and Bellaiche Y. Cell. 2013
  3. Dahman C. et al. Nat Rev Genet. 2011
  4. Inman A. and Smutny M. Semin Cell Dev Biol. 2021
  5. Shahbazi MN. et al. Science. 2019


  • Zebrafish embryo as model system: genetics (genome editing), transgenic lines.
  • Stem cell culture assays (ex vivo isolated cells, organoids), micropatterning.
  • Microscopy (live & fixed specimen): confocal and multiphoton microscopy, selective plane illumination (light sheet) microscopy
  • Optogenetics
  • Computational image analysis and statistics (Fiji, Matlab, R) of biological and physical processes (cell tracking; cell shape changes; protein and membrane dynamics; tissue, cell and nuclear mechanics).
  • Biophysical tools: cell confiner, atomic force microscopy, magnetic tweezer

Previous Projects

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