We engineer mammalian cells to self-organize into specific structures and patterns, a technology that will both teach us about natural patterning and will also lay the foundations for advanced tissue engineering.

Mammalian synthetic biology

We aim at engineering new synthetic gene circuits in mammalian cells: sensing modules, reporting modules and actuation modules (e.g. locomotion, apoptosis). Cells endowed with these new functions can be used to sense the presence of specific stimuli in their environment and report or act upon it.

Synthetic communication in mammalian cells: We engineer mammalian cells with sensing (synthetic receptors) and reporting circuits to detect specific cell-cell interactions. These synthetic communication systems allow us to study interactions between specific cell types both in vitro and in vivo, shading new light on intercellular processes. Synthetic morphology & patterning: We engineer mammalian cells to self-organize into specific structures and patterns. We built a pattern generator where cells self-organize in 2-D and 3-D based on phase separation and differential adhesion, and the resulting cell arrangements resemble animal coat patterns (Cachat et al. 2016, Sci. Rep. 6: 20664). By inducing specific morphogenetic circuits from a library of synthetic genetic modules we built previously (Cachat et al. 2014, J. Biol. Eng. 8: 26), we can add complexity to this pattern. For example, we can target one of the population to selectively undergo apoptosis (Cachat et al. 2017, Eng. Biol. 1-6), or target boundary cells to undergo specific differentiation. Although differential adhesion is a mechanism naturally occurring in developing tissues, it has not been identified as a pattern-generating mechanism in animals and as such constitutes a truly synthetic road to patterning. Another genetic machine we are building uses an architecture developed in theoretical terms in the 1950s by Alan Turing: the reaction-diffusion mechanism. Depending on system parameters, engineered cells should produce spots, stripes, swirls or travelling waves of activation. As opposed to the above patterning mechanism, the reaction-diffusion mechanism has been shown to drive patterning in developing embryos, but has not yet been reproduced synthetically. Together, these approaches will create simple systems to test existing theories of morphogenesis and patterning derived from the study of animal development but difficult to test in complex embryos. These approaches will also create synthetic platforms for use in tissue engineering, regenerative medicine and for the development of clinically-useful structures outside the normal developmental repertoire (Davies & Cachat 2016, Biochem. Soc. Trans. 44, 696-701).

Course organiser and Lecturer for 'Tools for Synthetic Biology' and 'Applications of Synthetic Biology' MSc courses.

Lecturer in The Microbial World 2.