Overview
How do physical forces and biochemical signals work together to shape early life? During early mammalian development, cells experience a rich environment of chemical and physical cues that guide how they grow, organise, and form body structures. While molecular signalling is well studied, we still know surprisingly little about how the physical environment - such as stiffness, structure, and mechanical forces - influences these developmental processes.
About this opportunity
To explore this, we can use gastruloids – 3D aggregates of embryonic stem cells that mimic many hallmarks of post-implantation development, including symmetry breaking, axis formation, and germ layer patterning. Gastruloids offer a powerful and ethical model to study early developmental processes in a controlled setting.
In this PhD project, you’ll combine biomaterials engineering with developmental biology to uncover how scaffold structure, stiffness, and biochemical signals together shape gastruloid development. Using advanced fabrication tools such as electrospinning and melt electrowriting, you’ll design fibrous and hydrogel-based scaffolds that recreate the complex physical and chemical environment of the embryo. This work will reveal how cells sense and respond to their surroundings – and could lead to new, reproducible tools for studying development, modelling disease, and testing biomaterials.
Research Aim and Hypothesis
The aim is to determine how the structural, mechanical, and biochemical properties of biomaterial scaffolds influence gastruloid cell fate and morphogenesis.
We hypothesise that scaffolds with well-defined architectures and controlled morphogen release will reproducibly guide gastruloid development, influencing symmetry breaking, axis formation, and lineage balance.
Objectives
Build a library of scaffolds with tuneable fibre diameter, alignment, porosity, stiffness, and hydrogel composition, incorporating systems for controlled release of key signalling molecules.
Optimise gastruloid culture on 2D and 3D scaffolds, monitoring development through live imaging and single-cell analysis.
Identify design principles linking scaffold structure, mechanics, and biochemical release profiles to developmental outcomes.
Methodology
You will fabricate and characterise scaffolds using electrospinning, melt electrowriting, and hydrogel crosslinking. Their properties will be analysed using scanning electron microscopy, mechanical testing, and rheology. Scaffolds will be functionalised for gradual release of morphogens such as Wnt, FGF, and TGFβ.
Mouse embryonic stem cells will be aggregated into gastruloids and cultured on or within the scaffolds. Development will be assessed via live imaging, immunofluorescence (e.g. Brachyury, Sox2, Sox17), and single-cell RNA sequencing.
Training and Development
This project provides interdisciplinary training at the intersection of developmental biology, stem cell biology, and biomaterials engineering. You’ll collaborate across life sciences and engineering and gain hands-on lab experience.
The project is well-suited to applicants from biology, biochemistry, or bioengineering backgrounds. You’ll develop a broad and adaptable skill set, including experimental design, data analysis, and scientific communication – valuable for both academic and industry careers.
Further reading
1. Bosworth LA, Lanaro M, O’Loughlin DA, D’Sa RA, Woodruff MA, Williams RL. Melt electro-written scaffolds with box-architecture support orthogonally oriented collagen. Biofabrication. 2021 Dec 30;14(1):015015.
2. Bosworth LA, Doherty KG, Hsuan JD, Cray SP, D’Sa RA, Pineda Molina C, Badylak SF, Williams RL. Material Characterisation and Stratification of Conjunctival Epithelial Cells on Electrospun Poly (ε-Caprolactone) Fibres Loaded with Decellularised Tissue Matrices. Pharmaceutics. 2021;13(3):318.
3. Lorenzo Lopez, M., Kearns, V.R., Curran, J.M. et al. Diffusion of nanoparticles in heterogeneous hydrogels as vitreous humour in vitro substitutes. Sci Rep 14, 17441 (2024).
4. Nian, S., Kearns, V.R., Wong, D.S., Bachhuka, A., Vasilev, K., Williams, R.L., Lai, W.W., Lo, A. and Sheridan, C.M., 2021. Plasma polymer surface modified expanded polytetrafluoroethylene promotes epithelial monolayer formation in vitro and can be transplanted into the dystrophic rat subretinal space. Journal of Tissue Engineering and Regenerative Medicine, 15(1), pp.49-62.
5. N2B27 media formulations influence gastruloid development. BioRxiv (2025; Soon to be published in Development); 10.1101/2025.03.15.643474.