The Molecular Nose
Lead Research Organisation:
Aston University
Department Name: Sch of Life and Health Sciences
Abstract
THE MOLECULAR NOSEMammalian cells use more genes to regulate biological processes than to carry them out. These include all fundamental processes such as cell growth, differentiation, survival, metabolism and the ability to sense and produce the correct complement of biomolecules to communicate with the environment. Complexity is further enhanced by the organization of biological processes as networks. Understanding the behaviour and responses of such complex networks will be crucial to solve eminent questions in biology. To address this need we will build a multiplexed sensor platform that can assess and quantify dynamic changes in the functional state of biochemical networks in mammalian cells, and use these data to reconstruct cell network interactions and their dynamic behaviour on a systems wide level. The concept underpinning this platform is fundamentally different from existing methods used in the biological sciences to assess cell function, and similar to the Electronic Nose , where an array of sensors is first trained with individual stimuli to establish a library of response patterns which subsequently are used to deconvolute complex inputs. The Molecular Nose will monitor the outputs of several hundred network components simultaneously in cell populations or single cells using artificial transcriptional reporters, and design a software framework and algorithms for their functional analysis. The Molecular Nose will be built in three versions. One will be constructed using molecular biology tools, and will permit to use a large array (up to 1000) of sensors. However, it requires the cell being lysed for the measurement as the detector is outside of the cell. This version will be particularly useful for training the system and establishing a large library of response patterns. The second version will be built by integrating both individual sensors and their corresponding detectors onto bar-coded nanoparticles which will be introduced into cells and read using surface enhanced resonance Raman scattering spectroscopy. This setup will use a smaller number of sensors (up to 30), but can be used to monitor responses in living cells in real time. In parallel we will develop methods for the controlled introduction of these particle libraries into cells. The third version is the stable integration of a plasmid based sensor library into the embryonic mouse stem cells with the aim to generate a transgenic sensor mouse. The stem cells also can be used for organotypic cultures and in vitro differentiation systems.The Molecular Nose will enable the systematic testing and rational interpretation of the behaviour of cellular networks. The technique is generic with a wide range of applications in both single cells and cell populations, including eminent biological problems such as the analysis of drug effects and prediction of side effects; stem cell differentiation with a view to eventually control differentiation; cell fate specification in order to support tissue engineering; genetic and biochemical networks for the production of desired proteins and metabolites by synthetically engineered pathways; and the investigation of adaptive network responses and evolution. Currently, we are lacking efficient experimental tools to analyse these complex interactions.
Organisations
Publications
Syme CD
(2012)
Quantitative characterization of individual microdroplets using surface-enhanced resonance Raman scattering spectroscopy.
in Analytical chemistry
Kremer C
(2014)
Shape-dependent optoelectronic cell lysis.
in Angewandte Chemie (International ed. in English)
Reboud J
(2013)
Acoustically controlled enhancement of molecular sensing to assess oxidative stress in cells.
in Chemical communications (Cambridge, England)
Sirimuthu NM
(2011)
Investigation of the stability of labelled nanoparticles for SE(R)RS measurements in cells.
in Chemical communications (Cambridge, England)
Barkess G
(2012)
Chromatin insulator elements: establishing barriers to set heterochromatin boundaries.
in Epigenomics
Graham D
(2011)
Combining functionalised nanoparticles and SERS for the detection of DNA relating to disease.
in Faraday discussions
Calderhead B
(2011)
Statistical analysis of nonlinear dynamical systems using differential geometric sampling methods.
in Interface focus
Zhong M
(2011)
Bayesian Methods to Detect Dye-Labelled DNA Oligonucleotides in Multiplexed Raman Spectra
in Journal of the Royal Statistical Society Series C: Applied Statistics
Yuan K
(2012)
Markov chain Monte Carlo methods for state-space models with point process observations.
in Neural computation
Hassan-Zadeh V
(2012)
USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator
in PLoS Biology
Ma MK
(2011)
Histone crosstalk directed by H2B ubiquitination is required for chromatin boundary integrity.
in PLoS genetics
Jiwaji M
(2014)
Quantification of functionalised gold nanoparticle-targeted knockdown of gene expression in HeLa cells.
in PloS one
Jiwaji M
(2012)
Unique reporter-based sensor platforms to monitor signalling in cells.
in PloS one
Reboud J
(2012)
Shaping acoustic fields as a toolset for microfluidic manipulations in diagnostic technologies.
in Proceedings of the National Academy of Sciences of the United States of America
Wrzesien J
(2012)
Synthesis of SERS active nanoparticles for detection of biomolecules
in Tetrahedron
Donaldson R
(2012)
Modular modelling of signalling pathways and their cross-talk
in Theoretical Computer Science
Stevenson R
(2011)
Nanoparticles and inflammation.
in TheScientificWorldJournal
Description | Some of the most important findings are: - new ways of detecting low levels of molecules in samples using silver nanoparticles - the use of surface acoustic wave technology in microfabricated diagnostics - the development of a reporter system for the detection of outputs from specific signalling pathways through transcription factor activation |
Exploitation Route | The SAW based diagnostics has now been protected and is in the process of being commercialised.. |
Sectors | Agriculture, Food and Drink,Chemicals,Communities and Social Services/Policy,Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
URL | http://www.aston.ac.uk/amr4amr |
Description | CDRL |
Amount | £3,885,167 (GBP) |
Funding ID | EP/I017887/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2011 |
End | 02/2016 |
Description | LSI Doctoral Training Centre |
Amount | £458,080 (GBP) |
Funding ID | BB/F529262/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2009 |
End | 08/2015 |
Description | Research Grant |
Amount | £92,340 (GBP) |
Funding ID | BB/J021172/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2012 |
End | 12/2013 |
Description | Research Grant |
Amount | £2,992,297 (GBP) |
Funding ID | EP/L014165/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2014 |
End | 04/2018 |
Description | Research Grant |
Amount | £184,690 (GBP) |
Funding ID | B/G006997/2 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2010 |
End | 04/2014 |
Description | Research Grant |
Amount | £249,035 (GBP) |
Funding ID | B/G006997/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2009 |
End | 11/2010 |
Description | Research Grant |
Amount | £681,191 (GBP) |
Funding ID | BB/J008605/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2012 |
End | 03/2016 |
Description | Sultanate of Oman |
Amount | £135,500 (GBP) |
Organisation | Oman - Ministry of Higher Education |
Sector | Public |
Country | Oman |
Start | 06/2012 |
End | 07/2016 |
Description | Technology Programme |
Amount | £898,862 (GBP) |
Funding ID | EP/K502303/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2012 |
End | 05/2015 |
Description | UCB Celltech |
Amount | £117,000 (GBP) |
Organisation | UCB Pharma |
Department | UCB Celltech |
Sector | Private |
Country | United Kingdom |
Start | 03/2012 |
End | 04/2016 |
Title | Assay assembly and method |
Description | The present invention relates to assay assemblies, components of assay assemblies, methods of determining one or more properties of a sample liquid, and methods of making components of assay assemblies. The present invention allows the properties of very small volumes of sample liquid to be probed, by providing a first surface having at least one sample liquid wettable surface region defined by a sample liquid repelling boundary, and a second surface, opposed to the first surface, having analyte binding agent immobilised thereon. |
IP Reference | WO2012/07298 |
Protection | Patent application published |
Year Protection Granted | 2013 |
Licensed | No |
Impact | Assay development has led to potential spin out. |
Title | FLUIDICS APPARATUS AND FLUIPICS SUBSTRATE |
Description | A fluidics apparatus is disclosed for manipulation of at least one fluid sample, typically in the form of a droplet. The apparatus has a substrate surface with a sample manipulation zone for location of the fluid sample. A transducer arrangement such as an interdigitated electrode structure on a piezoelectric body provides surface acoustic waves at the substrate surface for manipulation of the fluid sample. The substrate surface has an arrangement of surface acoustic wave scattering elements forming a phononic crystal structure for affecting the transmission, distribution and/or behaviour of surface acoustic waves at the substrate surface. Also disclosed is a method for lysing a cell. In this method, the cell is comprised in a fluid sample contacting a substrate surface, the method comprising providing surface acoustic waves at the substrate surface, such that the cell lyses. |
IP Reference | WO2011023949 |
Protection | Patent granted |
Year Protection Granted | 2011 |
Licensed | No |
Impact | Led to a number of additional findings and patents. Now being commercialised. |