We are a diverse team of scientists researching at the boundaries of engineering and biology to advance synthetic genomics and accelerate modular synthetic biology
By learning to engineer biology we can make breakthroughs in medicine materials and many other areas
Our lab's paper on Engineered Living Materials (ELMs) with the Tim Lu lab (@MIT) is now published in Nature Materials. Charlie Gilbert did a lot of this work back during his PhD in our group in collaboration with Tzu-Chieh Tang (Zijay) in Tim Lu's group in Boston. Wolfgang Ott and Will Shaw from our group also got involved over the years in this major project that was kickstarted by an MIT-Imperial MISTI Award.
ELMs have previously been created using non-food microbes like E. coli and filamentous fungi, but scalability – the potential for the technology to be produced on a larger scale – has always been a challenge, meaning ELMs aren’t yet widely used. Current ELM technologies also require trained personnel and stringent conditions to grow microbes, hindering their accessibility to the general public. We invented a new type of ELM to solve these problems by taking inspiration from the natural symbiotic approach of the kombucha SCOBY and combining genetically engineered yeast cells with cellulose-producing bacteria, making a ‘Syn-SCOBY’.
The Syn-SCOBY-produced cellulose acts as a scaffold which can hold the multi-functional enzymes produced by the yeast. This combination led us to be able to make programmable and tough materials easily at a large scale from cheap sugar mixtures.
Most importantly, because almost any version of yeast modified in the lab can be immediately used to produce kombucha-inspired materials in our system, dozens of different cell engineering options can be achieved in a ‘plug and play’ manner.
We created a material incorporating yeast that senses estradiol, a hormone which is sometimes found as an environmental pollutant, and produces GFP signal in response. We also engineered materials where the yeast within them secrete enzymes that break down antibiotics, pollutants and even the cellulose itself. Finally we even engineered the living material to respond to light and glow with luciferase in response.
The research was funded in part by the UK Engineering and Physical Sciences Research Council (EPSRC), U.S. Army Research Office, the MIT Institute for Soldier Nanotechnologies, and the MIT-MISTI MIT-Imperial College London Seed Fund.
Charlie Gilbert, Tzu-Chieh Tang, Wolfgang Ott, Brandon A. Dorr, William M. Shaw, George L. Sun, Timothy K. Lu, Tom Ellis (2021): Living materials with programmable functionalities grown from engineered microbial co-cultures. Nature Materials. https://doi.org/10.1038/s41563-020-00857-5
Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome. BA Blount, et al. Nat. Comms.
In this paper we use the SCRaMbLE system in Sc2.0 synthetic genome chromosomes to rapidly improve performance of heterologous metabolic pathways.
Burden-driven feedback control of gene expression.
F Ceroni, et al. Nature Methods
In this paper we use RNAseq to understand burden and develop a dCas9-based autofeedback controller to optimise cells.
Engineering a model cell for rational tuning of GPCR signaling.
W Shaw, et al. Cell
In this paper, we engineer a GPCR signalling pathway in yeast to enable rationally tunable biosensors for molecules relevant to human health.
Engineering control of bacterial cellulose production using a genetic toolkit and a new cellulose-producing strain.
M Florea, et al. PNAS
In this paper we build a genetic toolkit for a new bacterial cellulose producing bacteria
Biosynthesis of the Antibiotic Nonribosomal Peptide Penicillin in Baker’s Yeast.
AR Awan, et al. Nat. Comms.
In this paper we engineer yeast to produce Penicillin G using state of the art methods
Quantifying cellular capacity identifies gene expression designs with reduced burden.
F Ceroni, et al. Nature Methods,
In this paper we characterise the effect of DNA circuit design on the imposed burden on a cell