DNA-directed construction of three-dimensional photosynthetic assemblies

Lead Research Organisation: University of Strathclyde
Department Name: Pure and Applied Chemistry

Abstract

The aim of this project is to explore a completely new way of organising light harvesting modules where they can be placed in both two and three-dimensions with nanoscale precision. We will systematically investigate how the transfer of excitation energy from one light harvesting module to the next correlates to their overall arrangement within a DNA nanostructure. Going into the third dimension will be a key aim of this proposal since this will allow the building of larger cross-sections of absorbance. Any device that aims to use solar energy must harvest the light as a first step. As such, this proposal sets out to develop a new strategy to optimise the first step in this process.

Technical Summary

This research programme seeks to establish a working platform that will assemble photosynthetic proteins within DNA nanostructures. A hallmark of our approach is to use engineered photosynthetic proteins that selectively bind to target DNA sequences - both single-stranded and double-stranded - within a DNA nanostructure. This sequence selectivity directs the assembly of these proteins within a DNA matrix, thus providing spatial and positional control. Additional positional control of the overall nanostructure will then be imparted by directing the immobilization of the DNA-photosynthetic complexes by nanolithography. This bio-inspired platform methodology merges the principles of "bottom up" DNA nanotechnology with "top down" nanolithography and would provide the means to control, for the first time, the location of each photosynthetic protein module, inter-module distance and their relative orientation in both two- (2D) and three-dimensions (3D) along surfaces. Furthermore, this new design lexicon, if successful, will provide a framework to correlate how these parameters influence overall light harvesting efficiency.

Planned Impact

Potential Economic Impact of this Research

Synthetic Biology - One of the fundamental drivers of this research programme is the synthesis of modified DNA and DNA-binding molecules. Both synthetic aspects will deliver a battery of new methods to prepare novel compounds that could have wider economic impact on the Synthetic Biology and Diagnostic sectors of Life Science research beyond the lifespan of this 3 year project.

Diagnostics - New methodology to direct the assembly of DNA nanostructures on solid surfaces will pose additional benefits to the medical diagnostic sectors, particularly those directly associated with the identification of nucleic acid and protein biomarkers. It is envisaged that the benefits will arise from the development of new surface modification chemistries, new methods to incorporate functionality into DNA, which in turn could improve the sensitivity and selectivity of new biomolecular analytes and novel techniques to detect analytes using optical methods.

Outputs: Patent protection of Intellectual Property; exploration of licensees.

Mechanisms of delivering Economic Impact: UoS's and UoG's Knowledge Exchange partnership and Impact Acceleration Account (IAA), Scottish Enterprise Proof of Concept or the Technology Strategy Board's Biomedical Catalyst; Collaborative PhD students through Biomolecular Devices CDT (UoS).

Potential Societal Impact of this Research

This research describes a Synthetic Biology-inspired rationale to produce functional DNA nanostructures. Synthetic Biology has been designated a priority research area by the British Government and "has the ability to revolutionize major industries in bio-energy and bio-technology in the UK" (David Willets). At present, the application of Synthetic Biology techniques to create functional DNA-directed devices has not been recognized as a potential area for wider exploitation. Therefore the potential societal impact could be very significant. In order to prepare for this, public engagement with stakeholders associated with the field of UK Synthetic Biology would expedite acceptance of new and emerging applications.

Outputs: Public discussion of the role of Synthetic Biology and Nanotechnology in society; Dissemination of results through the mainstream press, UoG and UoS websites.
Mechanisms of delivering Societal Impact: Delivery of a Coffee House Lecture in Glasgow's City Centre; Involvement in Glasgow Science Festival and Glasgow Science Centre events.

Publications

10 25 50
 
Description This work has made us realise that the ability to immobilize DNA at a desired locationon a surface was critical to the success of the project. As a result, we have developed new immobilization techniques that could direct DNA nanostructures and proteins to a desired location on a surface. This involved exploiting the fluoruos effect and this technique has now been key to the wider objectives of this work. We have also gained further understanding of how photosynthetic proteins can bind to surfaces and DNA nanostructures by developing techniques to measure binding affinities of these complexes.
Exploitation Route New methods to immobilize material on surfaces for diagnostic applications.
Sectors Chemicals,Energy

 
Description This immobilization methods that were developed in this project have now been utilized for the development of fluorous-based immobilizaiton tools for nucleic acid detection.
First Year Of Impact 2019
Sector Healthcare
Impact Types Economic

 
Description BBSRC Responsive Mode
Amount £314,658 (GBP)
Funding ID BB/N016378/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description Collaboration with Institut Laue-Langevin 
Organisation Lohengrin (Institut Laue-Langevin)
Country France 
Sector Academic/University 
PI Contribution In collaboration with Armando Maestro and Nathan Zaccai, we have been successful in securing beamtime for netutron scattering experiments. The aim of this work is to determine the structural basis for how our photosynthetic fusion proteins containing a DNA binding domain bind to a target DNA sequence immobilized on a surface. In addition this work has enabled us to develop new fluorous based methods to immobilize DNA on a surface for this work.
Collaborator Contribution We have secured 2 beamtime slots. Return flights (2 people) and €1000 consumables were secured for each of the twotrips.
Impact No outputs as of yet
Start Year 2018
 
Description Invited presentation to fluorescence conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact An invited presentation at the Dynamic Biosensors annual meeting. This was used to showcase the potential of switchSENSE technology to obtain high quality data on the binding kinetics of small molecule-nucleic acids and nucleic acid interactions. the presentation was delivered to a blend of industrialists and academic groups.
Year(s) Of Engagement Activity 2017
URL https://www.dynamic-biosensors.com/user-meeting/
 
Description conference presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Fluorescent Biomolecules and their Building Blocks (FB3) conference is an internationally-renowned conference on the development of fluorescent tools and technology to probe the dynamics of biomolecules. I delivered an invited talk on our current work on the development of the development of DNA-directed photosynthetic assemblies.
Year(s) Of Engagement Activity 2018
URL http://www.rsc.org/events/detail/30910/fluorescent-biomolecules-and-their-building-blocks-fb3