Ellis:Research

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'''Latest Update: May 2012'''
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'''Latest Update: Dec 2012'''
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'''Investigating device-chassis interactions'''<br>
'''Investigating device-chassis interactions'''<br>
Project Type: ''Foundational''<br>
Project Type: ''Foundational''<br>
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Project Members: ''Rhys Algar, Wei Pan''<br>
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Project Members: ''Francesa Ceroni, Rhys Algar, Wei Pan''<br>
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Collaborators: ''Guy-Bart Stan, Microsoft''<br>
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Collaborators: ''Guy-Bart Stan''<br>
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 networks 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.
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 networks 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 gene networks and pathways'''<br>
'''Combinatorial modular assembly of gene networks and pathways'''<br>
Project Type: ''Foundational'' and ''Applied''<br>
Project Type: ''Foundational'' and ''Applied''<br>
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Project Members: ''Arturo Casini, Jaksa Novicic''<br>
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Project Members: ''Arturo Casini''<br>
Collaborators: ''Geoff Baldwin, James MacDonald''<br>
Collaborators: ''Geoff Baldwin, James MacDonald''<br>
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 and gene regulatory networks using standardized parts. As well as demonstrating a rapid new assembly technique, the project will yield synthetic cells with high production of high-value therapeutic molecules.
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 and gene regulatory networks using standardized parts. As well as demonstrating a rapid new assembly technique, the project will yield synthetic cells with high production of high-value therapeutic molecules.
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'''Standards and parts for synthetic biology'''<br>
 
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Project Type: ''Foundational''<br>
 
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Project Members: ''Georgios Pothoulakis, Nina Zhu, Anna Kress''<br>
 
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Collaborators: ''Richard Kitney, BIOFAB USA''<br>
 
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Synthetic biology requires professional characterisation of standardised parts to enable predictable and scalable construction of complex and robust devices and systems. Working in a collaboration with BIOFAB USA and Imperial's own BIOFAB group, we are developing new standards for part characterisation and genome design in E.coli, and new part libraries for engineering synthetic yeast.
 
'''Engineering thermophilic synthetic biology'''<br>
'''Engineering thermophilic synthetic biology'''<br>
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'''Parasite Protease Detection'''<br>
'''Parasite Protease Detection'''<br>
Project Type: ''Applied''<br>
Project Type: ''Applied''<br>
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Project Members: ''Nicolas Kylilis''<br>
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Project Members: ''Alex Webb''<br>
Collaborators: ''Paul Freemont, Geoff Baldwin, Bill and Melinda Gates Foundation''<br>
Collaborators: ''Paul Freemont, Geoff Baldwin, Bill and Melinda Gates Foundation''<br>
Almost all parasites release specific proteases during their life-cycle in order to invade and ingest surrounding tissues. Rapid, cheap detection of such proteases offers a novel method for diagnosis and tracking of parasistic disease, such as Schistosoma. Following on from Imperial's 2010 iGEM team and with generous funding from the Bill and Melinda Gates Foundation, we are developing a modular whole-cell biosensor solution to detect specific proteases released by parasites.
Almost all parasites release specific proteases during their life-cycle in order to invade and ingest surrounding tissues. Rapid, cheap detection of such proteases offers a novel method for diagnosis and tracking of parasistic disease, such as Schistosoma. Following on from Imperial's 2010 iGEM team and with generous funding from the Bill and Melinda Gates Foundation, we are developing a modular whole-cell biosensor solution to detect specific proteases released by parasites.
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'''Cyborg Biosensors'''<br>
 
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Project Type: ''Applied''<br>
 
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Project Members: ''Piotr Faba, Charles Fracchia''<br>
 
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Collaborators: ''Tony Cass, IBM''<br>
 
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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.
 

Revision as of 12:27, 3 December 2012

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Latest Update: Dec 2012


Research in the Ellis Lab focuses on advancing our understanding of nature through genome engineering and accelerating biotechnology through the use of synthetic biology. Projects are either foundational work, applied work or a nice mix of both.

Current Projects

Synthetic Yeast Chromosome XI
Project Type: Foundational and Applied
Project Members: Ben Blount, Dejana Jovicevic
Collaborators: Jef Boeke, Sc2.0 International Consortium
Sc2.0 is a high-profile, international project to do the first full synthesis of a eukaryotic cell genome, the model yeast species Saccharomyces cerevisiae. Led by Prof Jef Boeke at Johns Hopkins University, USA, an international consortium is now established to re-synthesis and make to design changes to all 16 yeast chromosomes. Our group is leading the UK effort in the consortium, aiming to design, synthesise and assemble the complete 666 kbp chromosome XI. During construction we will investigate genome design and topological effects such as nuclear structures and how these can be used to optimise gene expression in metabolic engineering.

Synthetic Biology with TAL-effector technology
Project Type: Foundational and Applied
Project Members: Ben Blount, Tim Weenink
TAL effectors are a relatively new form of DNA-binding protein that have a programmable DNA-recognition code. This means that they can be re-engineered repeatedly to bind to custom DNA sequences. We have now shown that modular TAL-effectors can be customised to be orthogonal repressors (TALORS) for yeast promoters - effectively acting as independent wires in logic systems. This offers a route to scalable logic systems in yeast synthetic biology. We are now looking to improve on this technology to generate a range of custom-built transcription factors which we can apply to advanced logic networks such as oscillators and memory systems.

Investigating device-chassis interactions
Project Type: Foundational
Project Members: Francesa Ceroni, Rhys Algar, Wei Pan
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 networks 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 gene networks and pathways
Project Type: Foundational and Applied
Project Members: Arturo Casini
Collaborators: Geoff Baldwin, James MacDonald
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 and gene regulatory networks using standardized parts. As well as demonstrating a rapid new assembly technique, the project will yield synthetic cells with high production of high-value therapeutic molecules.

Engineering thermophilic synthetic biology
Project Type: Foundational and Applied
Project Members: Elena Martinez-Klimova, Ben Reeve
Collaborators: David Leak, TMO Renewables
Engineering new function into well-characterised cells is one of the major goals of synthetic biology, but one phenotype almost impossible to add to cells like E.coli is thermostability. Instead, our lab is kick-starting synthetic biology in a Geobacillus species thermophile by developing standard measurement protocols with aerobic and anaerobic fluorescent proteins and charactersing libraries of standard, synthetic parts. We will use these to improve and diversify existing biofuel production pathways to generate high-yields and new products.

Parasite Protease Detection
Project Type: Applied
Project Members: Alex Webb
Collaborators: Paul Freemont, Geoff Baldwin, Bill and Melinda Gates Foundation
Almost all parasites release specific proteases during their life-cycle in order to invade and ingest surrounding tissues. Rapid, cheap detection of such proteases offers a novel method for diagnosis and tracking of parasistic disease, such as Schistosoma. Following on from Imperial's 2010 iGEM team and with generous funding from the Bill and Melinda Gates Foundation, we are developing a modular whole-cell biosensor solution to detect specific proteases released by parasites.

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