Molecular Machines that use structured DNA for directed movement

Lead Research Organisation: University of Portsmouth
Department Name: Sch of Biological Sciences

Abstract

We propose to develop a dynamic nanotool for use in drug discovery. This nanotool is based around a nanoactuator that uses a biological molecular motor to manipulate DNA and attached objects, in this case a magnetic bead. An electronic sensing system, based on MagnetoResistive (MR) devices will detect motion of the magnetic bead and output an electronic signal. Both the DNA and the motors can be targets for drugs, which means that the device can be used in screening drug-target interactions. The major advantage this system offers is single molecule detection and reporting of events, which will improve sensitivity to limits that are possible. The concept will be expanded by making novel use of branched and hairpin structures to provide information about position of binding of DNA-binding proteins, which will allow us to identify drugs targeted at non-motor DNA-binding proteins such as transcription factors.

Publications

10 25 50
publication icon
Brutzer H (2012) Scanning evanescent fields using a pointlike light source and a nanomechanical DNA gear. in Nano letters

publication icon
Chaves R (2011) Single molecule actuation and detection on a lab-on-a-chip magnetoresistive platform in Journal of Applied Physics

publication icon
Chaves R (2011) Low aspect ratio micron size tunnel magnetoresistance sensors with permanent magnet biasing integrated in the top lead in Journal of Applied Physics

publication icon
Ding F (2012) Single-molecule mechanical identification and sequencing. in Nature methods

publication icon
Evans L (2012) Enhanced purification and characterization of the PfeIF4A (PfH45) helicase from Plasmodium falciparum using a codon-optimised clone. in Protein expression and purification

publication icon
Firman K (2012) A Synthetic Biology Project - Developing a single-molecule device for screening drug-target interactions. in FEBS letters

publication icon
Freitas PP (2012) Spintronic platforms for biomedical applications. in Lab on a chip

publication icon
Manosas M (2012) Direct observation of stalled fork restart via fork regression in the T4 replication system. in Science (New York, N.Y.)

publication icon
Youell J (2012) Mechanistic insight into Type I restriction endonucleases. in Frontiers in bioscience (Landmark edition)

publication icon
Youell J (2011) Production and single-step purification of EGFP and a biotinylated version of the Human Rhinovirus 14 3C protease. in Protein expression and purification

 
Description University of Portsmouth
Amount £296,955 (GBP)
Funding ID IBBS PhD bursary and fees for 3 yrs to Luke Evans. 
Organisation University of Portsmouth 
Sector Academic/University
Country United Kingdom
Start 10/2009 
End 10/2012
 
Description Molecular Machines that use structured DNA 
Organisation Institute of Systems and Computer Engineering, Research and Development in Lisbon (INESC-ID)
Country Portugal 
Sector Charity/Non Profit 
PI Contribution DG is a biochemists and molecular biologist with a strong interest in developing biotechnology applications using expertise in DNA binding proteins.
Collaborator Contribution Our grant, 'Molecular Machines', involved an already-established and productive collaboration between four research teams based in the UK, France, Germany and Portugal, and built on developments from previous successful EU funding schemes (Mol-Switch and BioNano-Switch). The overall aim was to further develop a nanoactuator device for magnetoresistive (MR) sensing of molecular motor function and pursue how optical and magnetic tweezer set-ups, at the interface of biotechnology and electronic engineering, could be explored for new functions and uses in bionanotechnology.
Impact As listed in publications
Start Year 2009
 
Description Molecular Machines that use structured DNA 
Organisation Technical University of Dresden
Country Germany 
Sector Academic/University 
PI Contribution DG is a biochemists and molecular biologist with a strong interest in developing biotechnology applications using expertise in DNA binding proteins.
Collaborator Contribution Our grant, 'Molecular Machines', involved an already-established and productive collaboration between four research teams based in the UK, France, Germany and Portugal, and built on developments from previous successful EU funding schemes (Mol-Switch and BioNano-Switch). The overall aim was to further develop a nanoactuator device for magnetoresistive (MR) sensing of molecular motor function and pursue how optical and magnetic tweezer set-ups, at the interface of biotechnology and electronic engineering, could be explored for new functions and uses in bionanotechnology.
Impact As listed in publications
Start Year 2009
 
Description Molecular Machines that use structured DNA 
Organisation École Normale Supérieure, Paris
Country France 
Sector Academic/University 
PI Contribution DG is a biochemists and molecular biologist with a strong interest in developing biotechnology applications using expertise in DNA binding proteins.
Collaborator Contribution Our grant, 'Molecular Machines', involved an already-established and productive collaboration between four research teams based in the UK, France, Germany and Portugal, and built on developments from previous successful EU funding schemes (Mol-Switch and BioNano-Switch). The overall aim was to further develop a nanoactuator device for magnetoresistive (MR) sensing of molecular motor function and pursue how optical and magnetic tweezer set-ups, at the interface of biotechnology and electronic engineering, could be explored for new functions and uses in bionanotechnology.
Impact As listed in publications
Start Year 2009