A library of mammalian effector modules for synthetic morphology.

Elise Cachat,Peter Hohenstein,Jamie A Davies,Weijia Liu

doi:10.1186/1754-1611-8-26

Elise Cachat, Peter Hohenstein + Show 2 more

Open Access

https://doi.org/10.1186/1754-1611-8-26

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Abstract

BackgroundIn mammalian development, the formation of most tissues is achieved by a relatively small repertoire of basic morphogenetic events (e.g. cell adhesion, locomotion, apoptosis, etc.), permutated in various sequences to form different tissues. Together with cell differentiation, these mechanisms allow populations of cells to organize themselves into defined geometries and structures, as simple embryos develop into complex organisms. The control of tissue morphogenesis by populations of engineered cells is a potentially very powerful but neglected aspect of synthetic biology.ResultsWe have assembled a modular library of synthetic morphogenetic driver genes to control (separately) mammalian cell adhesion, locomotion, fusion, proliferation and elective cell death. Here we describe this library and demonstrate its use in the T-REx-293 human cell line to induce each of these desired morphological behaviours on command.ConclusionsBuilding on from the simple test systems described here, we want to extend engineered control of morphogenetic cell behaviour to more complex 3D structures that can inform embryologists and may, in the future, be used in surgery and regenerative medicine, making synthetic morphology a powerful tool for developmental biology and tissue engineering.Electronic supplementary materialThe online version of this article (doi:10.1186/1754-1611-8-26) contains supplementary material, which is available to authorized users.

Highlights

IntroductionThe formation of most tissues is achieved by a relatively small repertoire of basic morphogenetic events (e.g. cell adhesion, locomotion, apoptosis, etc.), permutated in various sequences to form different tissues
In mammalian development, the formation of most tissues is achieved by a relatively small repertoire of basic morphogenetic events, permutated in various sequences to form different tissues
We have proposed the construction of genetic modules for ‘synthetic morphology’: programming mammalian cells to display specific morphogenetic behaviours using synthetic biology principles, the eventual

Summary

Introduction

The formation of most tissues is achieved by a relatively small repertoire of basic morphogenetic events (e.g. cell adhesion, locomotion, apoptosis, etc.), permutated in various sequences to form different tissues. The aim of synthetic morphology is greatly aided by the observation that most normal mammalian morphogenesis seems to take place using about ten basic cellular behaviours, each tissue using them in different sequences and to different extents [7,9,10]. Synthetic biology offers new ways of studying complex systems by the bottom-up approach, i.e. dissecting a process into basic events/modules and combining them back up from scratch, building this process de novo, or at least part(s) of it. This way, engineered cells should be able to execute simple sequences of predetermined morphogenetic events and test theories of morphogenesis away from its complex, natural setting. The approach will allow researchers to explore what cells can do, rather than merely what they normally do

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