EASTBIO Forward engineering of pattern formation: Models and experiments towards predictive multicellular self-organisation

Background:
The aim of developmental biology is a complete understanding of how the embryo develops, how embryonic cells acquire their fate and how they arrange in time and space to create complex organisms.
Reverse engineering is the predominant approach in the field. Yet, a modern and complementary approach consists in applying forward engineering principles to biology:
instead of performing perturbation experiments in embryos or cell culture to pick apart the underlying mechanisms of development, forward engineering employs a bottom-up approach to devise biological systems with predictable properties. The implicit goal of this strategy is to gain quantitative insights into biological processes while at the same time exploring alternative designs not selected by evolution (Davies 2018, Tewary et al. 2018).

Project:
This PhD project aligns with the forward engineering mind-set.
We have recently shown that embryonic stem cells can form patterns spontaneously when the cells are confined in space in vitro (Blin et al, 2018). Recent preliminary work has focused on mathematical models offering plausible explanations for this process.
We can now take this research further:
The aim of this PhD project is to build novel theoretical models capable of describing the emergence of asymmetric patterns of cell fates from an initially homogenous population of cells
Key questions to address include:
• What is the minimal number of rules sufficient to elicit spontaneous symmetry breaking in a stem cell population?
• What are the key design principles that are necessary to confer robustness and plasticity to a patterning process?
• How do cues from the microenvironment (geometry, scale, chemistry) influence the patterning process designed during this project?
Importantly, the models created during this project will be experimentally tested using a combination of cell biology, quantitative imaging, micro-fabrication techniques and synthetic biology approaches available in the host lab

Impact:
This project will help us gain quantitative insights into the interplay between the various fundamental rules which are required to build a robust self-organised system. We will better understand the sensitivity of a developing multicellular system to the environment and its initial conditions. This will help us generate precise engineering guidelines for the production of bio-manufactured systems for medical applications (organ on chip or implantable mini-organs). We will also test current questions in systems and evolutionary biology.


Training:

The candidate will have the opportunity to be trained in the wet lab to test his/her own models experimentally, thus developing so-called T-Shaped skills (combining depth in one specialisation with the skill to collaborate across disciplines).
This will be enabled by a multidisciplinary team of supervisors dedicated to offer an environment that nurtures the candidate’s aspiration to become a skilled researcher who can work at the interface of several disciplines. The project is also sufficiently open to enable the candidate to become a creative thinker and develop and communicate his/her own ideas.