Using synthetic morphology to control cell-cell competition in mammalian tissues

This is a UK Centre for Mammalian Synthetic Biology Studentship.

Interested individuals must follow Steps 1, 2 and 3 at this link on how to apply:
http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply


Supervisors: V. Danos (School of Informatics), M. Cavaliere (School of Informatics), J.A. Davies and E. Cachat

During tumorigenesis, cancer cells reproduce more rapidly at the expense of neighbouring cells, even if this process is deleterious for the entire organism. Various types of cell-cell ecological interactions affect the spreading of tumors [1]. In particular, spatial, geometrical, and mechanical aspects of the tissues appear to have an important role in tumor evolution [1]. Recent experiments have shown that it is possible to program some of the geometrical and mechanical aspects of mammalian tissues using synthetic biology [2,3]. The objective of the PhD project is to investigate whether the ability to synthetically induce morphogenetic transformations in populations of mammalian cells could be used to alter the spreading of fast proliferating clones, and control the fate of tumors. The project couples modeling and experimental work. The plan is to simulate in-silico mechanical cell-cell interactions to provide novel insights on the role of cell elasticity and adhesion: preliminary in-silico results have already suggested the relevance of this last property in the spreading of fast-proliferating clones. The experimental part of the project will focus on this aspect using engineering of clones with inducible growth rates and inducible expression of two distinct types of cadherin molecules (Chd1 and Chd3) providing distinct level of cellular adhesion, leading to distinct patterning [2,3]. Synthetic cell types will be equipped with appropriate fluorescent reporter proteins to enable counting, tracking, and the detection of the evolution of patterns – this will allow to analyze the interplay between inducible geometric patterning and the spread of fast growing clones, during tissue proliferation. This project merges synthetic morphology with the idea of evolutionary dynamics and will advance our understanding and ability to control cell-cell competition, and the resilience of multicellularity to unbridled clone growth [1]. Applications to novel cancer therapies targeting cellular mechanics will be sought for.

The Phd candidate will be jointly supervised by V. Danos, M. Cavaliere (modelling) and J.A. Davies, E. Cachat (experimental part).


The PhD student will become part of a cohort of graduates students linked to the research of the new UK Centre for Mammalian Synthetic Biology (the ‘Centre’), based at the University of Edinburgh. Through support from the Research Council’s Synthetic Biology for Growth programme and of the BBSRC, EPSRC and MRC, the University has been awarded ~ £18M in funding to establish a national facility for DNA synthesis (the Edinburgh Genome Foundry) and one of six UK Centres of Excellence in Synthetic Biology. Edinburgh’s Centre embeds colleagues from the College of Medicine and Veterinary Medicine, in particular from the Scottish Centre for Regenerative Medicine. More information about our Centre can be found at http://www.synbio.ed.ac.uk and follow us on Twitter @SynthSysEd.


This is an exciting opportunity to be at the cutting edge of this fast moving area of science and technology in world-leading research institutes. We are looking for highly motivated graduates who are enthusiastic about the potential of this new area of science and keen to work across disciplines.