University of Edinburgh Featured PhD Programmes
Birkbeck, University of London Featured PhD Programmes
University of Warwick Featured PhD Programmes
University of Oxford Featured PhD Programmes
University of Leeds Featured PhD Programmes

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

  • Full or part time
    Dr G Blin
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

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. However, a modern and timely alternative 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 in the lab has focused on building mathematical models which offer 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 evolvability 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 new knowledge 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 and Environment

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 at the interface of several disciplines. The project is sufficiently open to enable the candidate to become a creative thinker and develop his/her own ideas.
The candidate will be based in the MRC-CRM in the Little France campus in Edinburgh and will be associated with the lab of quantitative biology of pattern formation (http://www.crm.ed.ac.uk/research/group/quantitative-biology-pattern-formation).
Our lab is a new multidisciplinary group focusing on the mechanisms of patterning during development and tissue regeneration. We work closely with the Schumacher group who develops mathematical models to formulate principles that apply to multiple biological systems in order to gain insight into misregulation in disease, and inform improvements to regenerative therapy (http://www.crm.ed.ac.uk/research/group/computational-biology-cell-populations).
The candidate will also benefit from close interaction with:
• The DARTH group located within walking distance from SCRM, focusing on state of the art signal processing and statistical machine learning techniques across diverse healthcare applications: https://www.darth-group.com/
• The Cachat lab part of the SynthSys institute (http://www.synthsys.ed.ac.uk/) which possesses cutting edge synthetic biology knowledge and technologies.

We are looking for an excellent candidate with a strong academic background in science and engineering with a genuine interest in developmental biology, tissue regeneration and more broadly to the way nature builds itself.
This project could suit an applicant with training in biology who is interested in learning mathematical or computational approaches, or an applicant with training in mathematics or computer science who is keen to develop an interest in biology.

Funding Notes

The “Visit Website” button on this page will take you to our Online Application checklist. Please complete each step and download the checklist which will provide a list of funding options and guide you through the application process.
If you would like us to consider you for one of our scholarships you must apply by 5 January 2020 at the latest.

References

Geometrical confinement controls the asymmetric patterning of brachyury in cultures of pluripotent cells.
Blin G, Wisniewski D, Picart C, Thery M, Puceat M, Lowell S.
Development. 2018 Sep 21;145(18). pii: dev166025. doi: 10.1242/dev.166025.

Using synthetic biology to explore principles of development.
Davies J.
Development. 2017 Apr 1;144(7):1146-1158. doi: 10.1242/dev.144196. Review.
PMID: 28351865

Stem cell bioengineering: building from stem cell biology.
Tewary M, Shakiba N, Zandstra PW.
Nat Rev Genet. 2018 Oct;19(10):595-614. doi: 10.1038/s41576-018-0040-z. Review.
PMID: 30089805

How good is research at University of Edinburgh in Biological Sciences?

FTE Category A staff submitted: 109.70

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities


FindAPhD. Copyright 2005-2019
All rights reserved.