Dr Michael Smutny

Supervisor Details

Contact Details

Warwick Medical School, University of Warwick

Scientific Background

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.

Research Groups

Wellcome-Warwick Quantitative Biomedicine Programme

Centre for Mechanochemical Cell Biology

Supervision Style

In three words or phrases: Supportive, goal-driven, collaborative.

Provision of Training

Your initial training will be supervised by me with support of experienced researchers in the lab, leading to more independence later.

Progression Monitoring and Management

I am here for advice and guidance to help you reach the goals we define together. Once more independent, I expect you to take ownership of your progression but to reach out to me when you need help or advise. I like to be kept up to date, and expect to see evidence of method development/data generation results on a flexibly defined time-basis. We will work out progression criteria together and we will always discuss a plan of action together which should enable you to reach your full potential.

Communication

Face2face/online/email/text. The team has a Slack group chat with which we regularly communicate during the week. Whilst I expect you to keep up with my/ team communications I assume that you manage your work/life balance. I am happy to discuss any issues that are impacting your ability to fulfil your potential or my/our expectations.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per fortnight

In year 3 of PhD study

At least once per fortnight

These meetings mainly face to face or online, and I am usually contactable for an instant response on every working day.

Working Patterns

The timing of work in my lab is relatively flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time. However, I expect students to be on site (lab or working rooms) during core hours (9-5pm) if not otherwise communicated.

Notice Period for Feedback

I need at least 2 weeks’ notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

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

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

Secondary Supervisor(s): Dr Martin Davey (Project 1), Dr Wolfram Gruhn (Project 2), Dr Falk Schneider (Project 3)

University of Registration: University of Warwick

BBSRC Research Themes:

Understanding the Rules of Life (Stem Cells, Systems Biology)
Integrated Understanding of Health (Regenerative Biology)

Project Outline

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 essential events 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. However, the precise molecular and cellular mechanisms regulating these processes in the early embryo are not well understood.

Project outlines

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

(Project 1) Mechanisms of cell elimination during development. Cell elimination is a fundamental process during health and disease which ensures that unwanted or dying (apoptotic) cells are removed from a tissue [2]. Although cell elimination has been extensively studied in the past in cultured epithelial tissues, we still know very little about the underlying mechanisms during embryonic development and how they can affect tissue and organ formation.

Objective – Determining molecular and cellular mechanisms of cell extrusion and clearance by non-immune cells in the developing zebrafish embryo.

Methods – In vivo and ex vivo live cell imaging (confocal, multiphoton) of cell elimination processes, biochemical perturbations (antisense oligonucleotides, drugs), computational image analysis, biophysical tools (cell stretcher, atomic force microscopy), transcriptomics (RNAseq).

(Project 2) Mimicking early brain development in a dish. Recent stem cell models (gastruloids, organoids) highlight the remarkable potential to recapitulate early embryonic development in vitro through an interplay of self-organisation and the extrinsic microenvironment [3]. Beside biochemical signalling, accumulating evidence indicate a crucial involvement of mechanical and geometrical cues in tissue patterning.

Objective – Establishing controlled conditions mimicking early embryonic brain development in vitro (zebrafish, human) and investigating the role of extracellular cues and tissue geometry in cell fate specification and tissue patterning.

Methods – 3D cell culture, live imaging and immunostaining (confocal, multiphoton), chemical and physical perturbations, computational image analyses of cell morphodynamics (movements, shapes), tissue patterning and biomaterials.

(Project 3) Feedback between cell fate specification and tissue morphogenesis. Cells can sense and respond to mechanical stimuli from the microenvironment. Yet, it is still unclear how embryonic stem (ES) cells interpret specific mechanical signals and integrate their response in cell and developmental programmes [4].

Objective – Identifying how mechanical signals regulate essential processes of early progenitor cells such as cell fate specification, cell division and segregation into distinct compartments.

Methods – Live imaging/immunostaining (confocal, multiphoton), quantitative image analysis of cellular morphodynamics (movement, shape), imaging of morphogen dynamics. Biophysical characterisation of cells in vivo and ex vivo.

References

[1] Gilmour D. et al. Nature. 2017.

[2] Ohsawa S. et al. Dev Cell 2018.

[3] Shahbazi MN. et al. Science. 2019.

[4] Collinet C, Lecuit T. Nat Rev Mol Cell Biol. 2021.

Co-supervisor on a project with Dr Darius Koester.

Previous Projects (2024-25)

Primary supervisor for:

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

Previous Projects (2023-24)

Primary supervisor for:

Understanding mechanisms driving tissue morphogenesis and cell fate during early embryonic development