Bio-engineering methods to quantify embryo mechanics

Project ID: 2228cd1435 (You will need this ID for your application)

UCL Lead department: Institute of Child Health

Project Summary:

Embryonic cells physically fold their tissues to form organ rudiments. One well-studied example is the neural tube, the precursor of the brain and spinal cord, which closes from a flat sheet of cells into a continuous tube. Failure of neural tube closure causes severe malformations such as spina bifida. The Galea lab uses physical and chemical engineering approaches to study the biomechanical basis of neural tube closure and causes of failed closure which produce spina bifida. We have recently developed a new technology which allows 3D printing of mechanical force sensors directly inside live-imaged embryos (see Maniou et al Research Square 2022, resubmitted following review to Nature Materials). This technology uses chemical engineering methods to additively manufacture elastic hydrogels with two-photon lasers precisely focused inside embryos. Deformation of elastic force sensors can be modelled with finite element modelling (FEM) to calculate forces applied by embryonic cells. This technique has allowed us to measure, for the first time, the dynamic evolution of mechanical forces during neural tube closure in chick embryos. We now want to extend this technology to enable its application to a mammalian system, which more closely resembles human neural tube closure. This would also allow its application to mouse models of spina bifida.

During the PhD, the student will: 1) Use FEM to rationally re-design force sensor shape to quantify mechanical forces generated during mouse spinal and cranial neural tube closure 2) Optimise 3D force sensor printing attached to growing mouse tissues using our established whole embryo culture method 3) Quantify mechanical force comparing embryos undergoing normal neural tube closure versus ones genetically predisposed to spina bifida

We ideally wish to appoint a student interested in the intersection between biology and engineering/physics eager to learn to work collaboratively, applying advanced microscopy and biomechanical approaches to studying morphogenesis.