A 2026 Crick PhD project with James Briscoe.

Project background and description

The transformation of uniform populations of cells into the diverse, spatially organised tissues of the vertebrate body represents one of nature's most remarkable engineering feats. This process occurs with extraordinary precision and reproducibility, yet the fundamental principles governing how molecular differentiation programmes integrate with biophysical mechanisms to sculpt tissue shape remain poorly understood. To elucidate these mechanisms, it is essential to map the dynamic relationships between cellular fate decisions and morphological changes: how do individual cells alter their properties during differentiation, and how do these changes propagate to drive tissue-scale morphogenesis?

A central component of this project will involve engineering predictable patterns of gene expression in embryonic stem cell-derived tissues to understand fundamental principles of developmental pattern formation. Rather than taking the traditional reductionist approach of disrupting molecular processes, this work will employ a rational design strategy that couples synthetic biology with developmental biology to test our understanding through construction. The project will focus particularly on the intersection of molecular and morphological mechanisms, investigating how intracellular gene regulatory networks integrate with extracellular signalling to produce complex, self-organising pattern-forming behaviours. By designing and building synthetic developmental systems with defined regulatory architectures, this approach will reveal the inherent trade-offs and design principles underlying natural patterning mechanisms.

This project will use in vivo and in vitro models of vertebrate tissue formation. These systems provide unprecedented experimental access to the coupled dynamics of differentiation and morphogenesis, allowing real-time observation of how shape emerges and feedback into gene regulatory networks across multiple spatial and temporal scales. The research will involve, cutting-edge single-cell genomics and imaging to reveal the fundamental relationships between molecular fate specification and biophysical state transitions at single-cell resolution. Micropatterning, optogenetic methods, and targeted perturbations will be used to dissect the multicellular feedback mechanisms that ensure robust tissue formation. The analysis will be integrated into a predictive computational framework that combines molecular and biophysical simulations. This will establish fundamental principles for how cycles of gene expression and morphogenesis drive complex tissue formation over extended developmental timeframes, providing new insights applicable to tissue engineering and regenerative medicine.

Candidate background

The project offers interdisciplinary training in cutting edge techniques in stem cell and developmental biology and will provide insight into the mechanisms and principles of the gene regulatory programmes that underpin tissue development. This will contribute to understanding the development of the spinal cord as well as shed light on broad principles of embryo development.

This project would suit a candidate interested in receiving interdisciplinary training in developmental and computational biology and will involve both experimental work and data analysis. The candidate will gain expertise in embryology, developmental biology, tissue culture, including embryonic stem cell differentiation, genome editing, molecular biology, flow cytometry, microscopy and biochemistry. This project would be suitable for anyone with an interest in cellular development and gene regulation, studying biological/biomedical sciences, or data science related subjects.

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