Professor Timothy Saunders

Supervisor Details

Contact Details

Warwick Medical School, University of Warwick

Scientific Background

Research Interests

How do your organs form? Each organ has a specific shape and size, that is optimised to ensure efficient function. In my lab, we study the biochemical and biophysical processes that lead to the shaping of organs. In particular, we explore how skeletal muscle and the heart form during development. We utilise model organisms such as zebrafish and fruit flies, in conjunction with quantitative live imaging, to develop biophysical models of organ shape morphogenesis.

Scientific Inspiration

D’Arcy Wentworth-Thompson and Alan Turing. They both realised the importance of applying mathematical and physical approaches to understand the process of morphogenesis in biology.

Research Groups

Saunders Lab

Supervision Style

In three words or phrases:

Supportive – I operate an open-door policy for students.
Goal driven – results (even when negative), not total time spent in the lab, is what matters.
Collaborative – I believe science works best when we work together as a team.

Provision of Training

At first, I meet students weekly for a formal meeting and have regular informal discussions (open-door policy). This ensures the student has regular guidance and support. By the third year of the PhD, students should be more independent, with meetings once every two weeks typically.

In my lab, each student typically has a post-doc or senior student who works with them in their first year.

I encourage students to interact with others in their cohort to troubleshoot problems. More is learnt by trying by yourself or with other students rather than going straightaway to someone more experienced for the answer.

Progression Monitoring and Management

I like to be kept up to date on progress, but I am not a micro-manager. At our weekly meetings, I do not expect to see significant advances each time. For example, the discussion can include going through what is learnt in courses.

Students should take ownership of their projects. Though you will work with a post-doc or senior graduate student, you will have a distinct project that is yours. It is also important that you view the project as not set in stone, and you can suggest possible new directions or approaches.

I am here for advice and guidance to help you reach the goals you set for yourself.

Communication

I make extensive use of Slack and email in communicating with the lab. I can message at any time, but I do not expect an instant reply.

I expect students to be organised. They should keep a calendar to make sure they do not miss deadlines or meetings.

I am happy to discuss any issues that are impacting your ability to fulfil your potential or my/our expectations. I believe in discussing problems early with a constructive mindset towards problem solving.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD

At least once per week (except when the student is attending many courses, then we meet fortnightly)

In year 2 of PhD

At least once per fortnight

In year 3 of PhD

At least once per fortnight (it may be less frequent depending on progress)

These meetings will be mainly face to face, and I am usually contactable for a quick response on 4-5 days per week.

Work Patterns

The timing of work in my lab is flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time. However, I strongly discourage working at night except when absolutely necessary. Animal care will require specific timetables to be kept.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Building the first heart vessel

Secondary Supervisor(s): Dr Andrew Nelson

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

How does the heart form? Despite the large array of adult heart morphologies across nature, the initial heart tube typically forms as a simple tubular structure. Further, the genetic network underlying the specification of the early embryonic heart is highly conserved across species.¹

In this project, we will use the power of human-derived organoid systems (coined cardioids) and live imaging to unravel the fundamental mechanical and genetic mechanisms driving the formation of the initial heart tube.^2-4 What are the mechanical processes building the first heart structures, such as the lumen?

We will begin by establishing cardioids^5,6 in the Saunders lab, with support from the co-supervisors Assoc Prof Nelson and Dr Simões. Assoc Prof Nelson brings expertise in stem cell systems genetics and bioinformatic approaches.⁷ Dr Simões is a world-leading expert in heart development and has developed 3D in vitro organoid systems of the human heart. She co-leads the Oxford Organoid Hub. The first aim will be to develop imaging approaches to enable live imaging of the cardioids. This will involve using a range of microscopes (spinning disc, 2-photon, light-sheet). Combined with advanced image analysis methodologies,⁶ this exciting approach will enable unprecedented insight into the dynamics of the formation of the initial heart structure.

The project will explore which mechanical components (e.g., cell cytoskeleton, filopodia, actin, microtubules) are essential in building the early heart tube. We will initially focus on identifying how perturbations to, for example, cadherins, alter the dynamics of heart lumen formation. The student will build the first dynamic atlas of the processes underlying the formation of the very first human heart structures. Importantly, we will link this to genomic information from Dr Simōes lab. How are the gene regulatory circuits driving formation of the early heart structures accommodating for dynamical mechanical cues? Can we find signatures of feedback between mechanical and genomic processes?

As part of the project, there will be opportunities to visit the Institute of Developmental and Regenerative Medicine at Oxford University to learn techniques and gain insights from experts in heart development. Further, we have a collaboration with Dr Kate McDole at the MRC LMB in Cambridge, where we will use light-sheet microscopy to image the cardioids.

This PhD project offers an exciting opportunity to leverage recent advances in live imaging, organoids and genetics to gain unprecedented insights into how a critical organ forms during development, with potential impact on human health.

This project is a truly interdisciplinary project, ideally suited for either (a) a trained biologist interested in developing their expertise in quantitative approaches or (b) a physicist or engineer (preferably with some optics experience) interested in applying the latest microscopy approaches to important biological systems.

Methodologies that will be developed as part of the project:

1) Human pluripotent stem cell-derived 3D organoids. This will include learning to maintain and differentiate iPS cells, micropatterning and performing perturbations.

2) Live imaging. We will utilise multiphoton microscopy and light-sheet microscopy to gain a subcellular view of how the heart initially forms.

3) Image analysis. Taking data from our microscopy and generating quantitative data is essential. In particular, we want to understand the specific developmental time when morphological changes occur.

4) Mechanobiology approaches to understanding cell function and morphology.

The Saunders lab is a highly interdisciplinary environment, with biologists and physicists working together to tackle major questions concerning how organs form. The Simōes lab is world-leading in heart development. This project offers a motivated student the opportunity to learn a breadth of techniques in quantitative biology that have broad applicability. It will run in parallel with the lab’s British Heart Foundation supported research dissecting the genetics of heart formation.

References

1. Olson EN, Gene regulatory networks in the evolution and development of the heart. Science 2006; 313: 1922

2. 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

3. 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

4. Zhang S and Saunders TE. Mechanical processes underlying precise and robust cell matching. Seminars in Cell and Developmental Biology 2021; 120:75

5. Lewis-Israeli, Yonatan R., et al. Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nature communications 2021; 12: 5142

6. Hofbauer, P. et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell 184, 3299-3317 e3222 (2021).

7. Johal, S., Elsayed, R., Panfilio, K. A. & Nelson, A. C. Identifying the molecular basis for functional divergence of duplicated SOX factors controlling endoderm formation and left-right patterning in zebrafish Biorxiv (2024).

Techniques

The project is inherently multidisciplinary. It combines live imaging, image analysis, mechanobiology and developmental biology. A successful student will learn a range of key skills, including in genetics, stem cell biology, computational analysis, biophysics, and imaging.

Co-supervisor on a project with Dr Andrew Nelson.

Previous Projects (2024-25)

Primary supervisor for:

Building the first heart vessel

Co-supervisor on a project with Dr Andrew Nelson.

Previous Projects (2023-24)

Primary supervisor for:

Building the first heart vessel