Ellis:Research

Latest Update: June 2011

Research in the Ellis Lab focuses on advancing biotechnology through the use of synthetic biology. Projects fall into one of two categories or belong in both:

Developing the tools for rapid, predictable engineering of biological devices and systems.
 * 1. Foundational Synthetic Biology

Examples: biopart design, assembly techniques and device synthesis, part and device characterisation, standardisation, chassis systems, mathematical models, design simulations

Using the synthetic biology approach in biotechnology applications.
 * 2. Applied Synthetic Biology

Examples: combinatorial synthesis of pathways, modular design of biosensors, cheap inducer systems for biosynthesis

Current Projects
Investigating device-chassis interactions Project Type: Foundational Project Members: Rhys Algar, Hung Hsu Collaborators: Guy-Bart Stan Most gene devices demonstrated in synthetic biology have been high-expression strength regulatory networks hosted on mid-to-high copy number plasmids in E.coli. Despite being relatively simple and small, these devices are thought to be close to the maximum tolerated by the host cell - if they were any larger they would impinge on the host cell's own mechanisms. In this project, we are trying to quantify the threshold for gene device cloning into the E.coli chassis by examining a standard synthetic feed-forward loop motif expressed at a variety of different strengths in plasmid systems of varying copy number. The intention is to define a quantitative standard for inserting gene devices into chassis cells and build a predictive model to aid future design.

Combinatorial modular assembly of diverse Carotenoid production pathways in yeast Project Type: Foundational and Applied Project Members: Arturo Casini Collaborators: Geoff Baldwin The availability of gene synthesis is increasing rapidly, yet there is no straightforward lab-bench method to arrange modular gene units into larger assemblies with pre-defined positions. In this project we will demonstrate a new method to rapidly assemble gene units in a pre-defined order and showcase the technique to combinatorially assemble diverse synthesis pathways in yeast. The modular gene units from the carotenoid pathways are driven by regulated promoters from a pre-existing library, and combinatorial assembly with these will produce pathways with a variety of metabolic fluxes. As well as demonstrating a rapid new assembly technique, the project will yield synthetic yeasts with high production of high-value carotenoid molecules.

Bottom-up design of orthogonal E.coli promoters Project Type: Foundational Project Members: Fabio Chizzolini Synthetic biology has made great advances in its first decade but the complexity of devices has not exploded exponentially as expected. One of the major reasons for this is the lack of different parts, and specifically a dearth of regulated promoters is holding synthetic biology back. In E.coli our understanding of these promoters is advancing fast enough to consider building them up from scratch, but where do we start? In this project we will evolve a new orthogonal promoter system that uses a mutated Sigma Factor and mutated core promoter DNA sequence, so that these designer promoters are only recognised by the designer sigma factor under our control. This will lay the foundation for building a whole set of 'synthetic biology ONLY' promoters and devices that can sit in cells and yet only have limited interaction with the host cell systems.

New standards for BIOFAB projects Project Type: Foundational Project Members: Ben Blount, Serge Vasylechko, Riham Satti Collaborators: Richard Kitney, BIOFAB USA Synthetic biology requires professional characterisation of standardised parts to enable predictable and scalable construction of complex and robust devices and systems. To characterise biological parts it is useful to have a reference standard part to which it can be compared. This has been demonstrated by Kelly et al. for housekeeping promoters in E.coli. Working in a collaboration with BIOFAB USA and Imperial's own BIOFAB group, we are developing two new standards for part characterisation: (1) a standard reference promoter for yeast selected from systems biology screening, and (2) an ultra-efficient GFP coding region with various degradation tags for dynamical characterisation at low copy numbers. Cyborg Biosensors Project Type: Applied Project Members: Charles Fracchia Collaborators: IBM A single E.coli cell can sense subtle changes in its environment such as the presence of pollutants or rare metals, however it takes millions of E.coli, all producing fluorophores or dyes to relay this message back to a human eye. To tackle this scale-barrier between the microbe world and human world we're developing a simple genetic part that gives an output that can be recorded by cheap nanotechnology detectors. A cyborg scheme interfacing disposable electronics with re-programmable microbes will offer low-cost, high-sensitivity environmental sensing solutions.

Degrade-and-Fire Oscillations at the Nucleus Project Type: Foundational Project Members: Tim Weenink Collaborators: Mauricio Barahona, Andrew DeMello Yeast, like all eukaryotic cells, spatially separates its DNA from its protein synthesis machinery. The spatial separation offers a time-delay window where transcription factors are synthesised in the cytosol but take time to translocate to through the nuclear envelope to their site of action. In this project we are exploiting this phenomenon to produce a simple degrade-and-fire oscillator system where oscillations are determined by nuclear transport efficiency and protein degradation speeds. We intend to model our system and use microfluidics to characterise individual cells in phase.