A three-step framework for programming pattern formation

Abstract

The spatial organisation of gene expression is essential to create structure and function in multicellular organisms during developmental processes. Such organisation occurs by the execution of algorithmic functions, leading to patterns within a given domain, such as a tissue. Engineering these processes has become increasingly important because bioengineers are seeking to develop tissues ex vivo. Moreover, although there are several theories on how pattern formation can occur in vivo, the biological relevance and biotechnological potential each of these remains unclear. In this review, we will briefly explain four of the major theories of pattern formation in the light of recent work. We will explore why programming of such patterns is necessary, while discussing a three-step framework for artificial engineering approaches.

Key Features of Turing Systems are Determined Purely by Network Topology

“…This evidence is, however, not indisputable. There have been many attempts to engineer synthetic networks in a field of cells to produce a Turing pattern of gene expression, but none has succeeded in providing the definitive experimental demonstration [58]. In part, the difficulty stems from the fact that most efforts have followed the designs of classic Turing networks [40].…”

Turing patterns are common but not robust

“…While a rich mathematical literature on Turing patterns exists, the vast majority of studies analyze single, idealized networks with fixed parameters (Gaffney, Yi, and Lee, 2016;Iron, Wei, and Winter, 2004;Liu et al, 2013). Although these studies have significantly increased our understanding of patterning mechanisms, they do not provide general guidelines for either the identification of naturally evolved Turing networks in biological systems, or for synthetic engineering of TP networks (Scholes and Isalan, 2017;Borek, Hasty, and Tsimring, 2016;Carvalho et al, 2014;Duran-Nebreda and Solé, 2016;Boehm, Grant, and Haseloff, 2018;Cachat et al, 2016;Diambra et al, 2015;Cachat et al, 2016). A recent approach which has proved very successful in increasing our understanding of biological design principles is the "network atlas" approach (Babtie, Kirk, and Stumpf, 2014;Ma et al, 2009).…”

“…There is growing interest in synthetic biology to engineer patterning systems from first principles (Basu et al, 2005;Schaerli et al, 2014;Borek, Hasty, and Tsimring, 2016;Carvalho et al, 2014;Duran-Nebreda and Solé, 2016;Boehm, Grant, and Haseloff, 2018;Cachat et al, 2016). Artificial TPs are expected to have eventual applications in nanotechnology, tissue engineering and regenerative medicine (Scholes and Isalan, 2017;Tan et al, 2018). Despite much effort in this area, engineered TPs remain elusive.…”

Engineered cell-to-cell signalling within growing bacterial cellulose pellicles

“…In most natural systems that produce biomaterials, communication between materialproducing cells is a critical component of producing materials with structures on the micro and macro scale. ELMs research can theoretically recapitulate this in material-producing bacteria by leveraging the significant past work done to engineer Escherichia coli for synthetic pattern formation (Scholes et al, 2017). Such engineered pattern formation work typically exploits quorum-sensing systems from various bacteria, which are a natural method of bacterial cell-to-cell communication that can be reprogrammed (Scholes et al, 2017).…”

“…ELMs research can theoretically recapitulate this in material-producing bacteria by leveraging the significant past work done to engineer Escherichia coli for synthetic pattern formation (Scholes et al, 2017). Such engineered pattern formation work typically exploits quorum-sensing systems from various bacteria, which are a natural method of bacterial cell-to-cell communication that can be reprogrammed (Scholes et al, 2017). The Lux quorum-sensing system from Vibrio fischeri is particularly well-used in this context, utilising the signalling molecule 3OC6-HSL -often referred to generally as acyl-homoserine lactone (AHL) (Churchill et al, 2011).…”