Translation Grant for The HIPER project - Bringing the NMR Paradigm to ESR
Lead Research Organisation:
University of St Andrews
Department Name: Physics and Astronomy
Abstract
In the original Basic Technology program Bringing the NMR Paradigm to ESR technology was developed to deliver complex sequences of very high power mm-wave pulses with sub-nanosecond resolution to a small sample in a strong magnetic field and measure a response from the sample 13 orders of magnitude lower in power, within 1 nanosecond of the final pulse. This was widely regarded as impossible by many leading members of the ESR instrumentation community three years ago. However, after two years developing the necessary mm-wave technologies and one year integrating them into a fully working system, the instrument is now demonstrating these very high levels of performance.The success of that program now opens up major new opportunities in the understanding of fast chemical and biochemical processes and in dramatically improving the sensitivity and resolution of techniques to understand local structure around paramagnetic centres, which often play a central role in determining the catalytic, enzymatic, electronic and optical properties of important chemical, biological and technological systems. It also promises to significantly improve the sensitivity of Site-Directed Spin Labelling techniques that promise to become a generic tool in the understanding of the structure, dynamics, conformational changes, interactions and function of important biomolecules in complex biomolecular processes. The aim of this Translation Grant is to provide underpinning but flexible support that will allow us to fully exploit this technological breakthrough via a series of pilot projects and collaborations.
Publications
Abdullin D
(2014)
Geometric model-based fitting algorithm for orientation-selective PELDOR data
in Molecular Physics
Bowman A
(2011)
The histone chaperones Nap1 and Vps75 bind histones H3 and H4 in a tetrameric conformation.
in Molecular cell
Cruickshank PA
(2009)
A kilowatt pulsed 94 GHz electron paramagnetic resonance spectrometer with high concentration sensitivity, high instantaneous bandwidth, and low dead time.
in The Review of scientific instruments
Dabb S
(2015)
mer and fac isomerism in tris chelate diimine metal complexes
in Dalton Transactions
Giannoulis A
(2018)
Orientation selection in high-field RIDME and PELDOR experiments involving low-spin CoII ions.
in Physical chemistry chemical physics : PCCP
Jelinska C
(2010)
Dimer-dimer stacking interactions are important for nucleic acid binding by the archaeal chromatin protein Alba.
in The Biochemical journal
McKay J
(2013)
Compact Wideband Corrugated Feedhorns With Ultra-Low Sidelobes for Very High Performance Antennas and Quasi-Optical Systems
in IEEE Transactions on Antennas and Propagation
McKay J
(2016)
Compact Corrugated Feedhorns With High Gaussian Coupling Efficiency and $-60\;\text{dB}$ Sidelobes
in IEEE Transactions on Antennas and Propagation
Motion CL
(2016)
DEER Sensitivity between Iron Centers and Nitroxides in Heme-Containing Proteins Improves Dramatically Using Broadband, High-Field EPR.
in The journal of physical chemistry letters
Reginsson GW
(2012)
W-band PELDOR with 1 kW microwave power: molecular geometry, flexibility and exchange coupling.
in Journal of magnetic resonance (San Diego, Calif. : 1997)
Song L
(2016)
Toward increased concentration sensitivity for continuous wave EPR investigations of spin-labeled biological macromolecules at high fields.
in Journal of magnetic resonance (San Diego, Calif. : 1997)
Stevens MA
(2016)
The use of the Rx spin label in orientation measurement on proteins, by EPR.
in Physical chemistry chemical physics : PCCP
Thomson S
(2017)
Air exposure induced recombination in PTB7:PC 71 BM solar cells
in Journal of Materials Chemistry A
Zhang W
(2013)
Structural plasticity of histones H3-H4 facilitates their allosteric exchange between RbAp48 and ASF1.
in Nature structural & molecular biology
| Description | This project has developed new electron magnetic resonance instrumentation that increased the volume sensitivity by over an order of magnitude compared to standard commercial instruments, whilst improving time and spectral resolution. This instrument has won international awards and has resulted in many commercial sales. It is primarily used as a tool in molecular biology to understand large scale structure and interactions in proteins. Many of the technologies developed have been used within our radar programs. Multiple systems have been sold and the technologies developed used in many other research programs (radar, space, metrology). The instrument is currently demonstrating state of the art sensitivity and the new program is poised to improve this further. This has implications for in-cell molecular probes currently limited by sensitivity. |
| Exploitation Route | The new instrumentation, showed for the first time (against predictions in the literature) that it is possible to dramatically improve sensitivity in electron magnetic resonance experiments - which is the central grand challenge in this field. It achieved this by exploiting and developing new technologies and methodologies. We demonstrated gains in sensitivity by a factor of 30 and showed it was possible to measure signals during high power pulses. The current EPR instrumentation supports the work of a large group of EPR research scientists from St Andrews and Dundee and their National and International collaborators. Many of the technologies developed are used in related radar programs. Our commercial partner Thomas Keating Ltd have sold multiple commercial systems to international customers. We have just had a new EPSRC grant accepted to increase sensitivity by another factor of 30. At this level we should be able to detect spin labelled proteins at natural concentration in cells, detect defects at natural concentration levels in many common types of electronic thin film devices and look for trace radicals in large volume samples. |
| Sectors | Chemicals,Electronics,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| URL | http://www.st-andrews.ac.uk/~mmwave/ |
| Description | Over £2M in international commercial sales by our commercial partner Thomas Keating on mm-wave instrumentation, developed during the grant including a full system to the US National High Magnetic Field Laboratory in Florida and a partial system to PNNL in Washington State. Components developed under the Basic Technology program continue to be used by our commercial partner in a wide variety of instrumentation programs (metrology, space, radar, radiometry). Thomas Keating has sold EPR/DNP systems to approximately 10 major groups in Europe and 10 major groups in the US, and was awarded the Queens Award for Industry in 2012, with one third of turnover being directly attributed to magnetic resonance. |
| Sector | Electronics,Manufacturing, including Industrial Biotechology |
| Impact Types | Economic |
| Description | Action Research Wellcome Trust |
| Amount | £580,764 (GBP) |
| Funding ID | Multi User Equipment Grant 099149/Z/12/Z |
| Organisation | Imperial College Healthcare NHS Trust |
| Department | Ovarian Cancer Action Research Centre (OCARC) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2012 |
| End | 08/2017 |
| Description | Action Research Wellcome Trust |
| Amount | £1,400,000 (GBP) |
| Funding ID | Wellcome Trust |
| Organisation | Imperial College Healthcare NHS Trust |
| Department | Ovarian Cancer Action Research Centre (OCARC) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Description | Action Research Wellcome Trust |
| Amount | £580,764 (GBP) |
| Funding ID | Multi User Equipment Grant 099149/Z/12/Z |
| Organisation | Imperial College Healthcare NHS Trust |
| Department | Ovarian Cancer Action Research Centre (OCARC) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2012 |
| End | 08/2017 |
| Description | BBSRC Grouped |
| Amount | £1,725,000 (GBP) |
| Funding ID | BB/H017917/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | EPSRC |
| Amount | £15,000 (GBP) |
| Funding ID | EPSRC Strategic Partnership Fund |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2011 |
| End | 06/2012 |
| Description | EPSRC |
| Amount | £731,447 (GBP) |
| Funding ID | EP/R013705/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2017 |
| End | 11/2018 |
| Description | EPSRC |
| Amount | £3,000,000 (GBP) |
| Funding ID | CDT-lite scheme |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2008 |
| End | 09/2017 |
| Description | EPSRC |
| Amount | £52,536 (GBP) |
| Funding ID | Sub-contract with Manchester |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2011 |
| End | 06/2012 |
| Description | EPSRC |
| Amount | £182,257 (GBP) |
| Funding ID | Outreach Grant |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2010 |
| End | 03/2013 |
| Description | EPSRC IAA |
| Amount | £17,567 (GBP) |
| Funding ID | EP/R511778/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2017 |
| End | 09/2018 |
| Description | EPSRC IAA |
| Amount | £22,386 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2016 |
| End | 03/2017 |
| Description | EPSRC IAA |
| Amount | £23,071 (GBP) |
| Funding ID | EP/R511778/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2018 |
| End | 03/2019 |
| Description | European Commission (EC) |
| Amount | £836,853 (GBP) |
| Funding ID | 312745 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | |
| Description | Home Office |
| Amount | £49,602 (GBP) |
| Funding ID | HOS/12/024 |
| Organisation | Home Office |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2013 |
| End | 09/2013 |
| Description | Medical Research Council |
| Amount | £438,880 (GBP) |
| Funding ID | MRC Project Grant |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2011 |
| End | 12/2013 |
| Description | Thales Ltd |
| Amount | £21,991 (GBP) |
| Funding ID | P O 7038156 |
| Organisation | Thales Group |
| Sector | Private |
| Country | France |
| Start | 01/2013 |
| End | 09/2013 |
| Description | Thomas Keating Ltd |
| Amount | £40,000 (GBP) |
| Funding ID | Royalties |
| Organisation | Thomas Keating Ltd |
| Sector | Private |
| Country | United Kingdom |
| Start | |
| Description | Thomas Keating Ltd |
| Amount | £40,000 (GBP) |
| Funding ID | Royalties |
| Organisation | Thomas Keating Ltd |
| Sector | Private |
| Country | United Kingdom |
| Start | |
| Description | US Army Research Laboratory |
| Amount | £62,515 (GBP) |
| Funding ID | W911NF-12-1-0535 |
| Organisation | US Army Research Lab |
| Sector | Public |
| Country | United States |
| Start | 09/2012 |
| End | 03/2013 |
| Description | US National High Magnetic Field Lab |
| Amount | £1,100,000 (GBP) |
| Funding ID | HIPER |
| Organisation | US National High Magnetic Field Laboratory |
| Sector | Public |
| Country | United States |
| Start | 12/2011 |
| End | 01/2013 |
| Description | US National High Magnetic Field Lab |
| Amount | £1,100,000 (GBP) |
| Funding ID | HIPER |
| Organisation | US National High Magnetic Field Laboratory |
| Sector | Public |
| Country | United States |
| Start | 09/2011 |
| End | 09/2013 |
| Description | US National High Magnetic Field laboratory |
| Amount | £99,990 (GBP) |
| Organisation | Florida State University |
| Sector | Academic/University |
| Country | United States |
| Start | 01/2015 |
| End | 04/2016 |
| Title | Orientational PELDOR |
| Description | The method uses the resolution and sensitivity available at high magnetic fields to determine the relative orientation (and associated distribution) of spin labels attached to biological samples |
| Type Of Material | Biological samples |
| Year Produced | 2009 |
| Provided To Others? | Yes |
| Impact | It is now an established method - although the impact is likely to be in the next few years with the development of more rigid spin labels. |
| Description | Thomas Keating Ltd |
| Organisation | Thomas Keating Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | We were joint partners under the original Basic Technology Program. The overall system design and design of many critical components were made by the group at St Andrews. |
| Collaborator Contribution | Thomas Keating supplied expertise in manufacturing and in some component design and provided a commercial route to exploit the technologies. |
| Impact | Over £2M in instrumentation and component sales related to technologies and instrumentation developed under the grant. In 2012 Thomas Keating Ltd won the Queens Award for Industry - for exports - one third was attributed to suppling magnetic resonance instrumentation. Sales to groups in Europe include: CNRS Grenoble, EPFL Lausanne, Heidelberg, Pisa, Saclay, Nottingham, Warwick, Weizmann Institute, Mulheim, Berlin, Stuttgart, Frankfurt Sales in the US include: MIT, NHMFL, Cornell, Yale, UF Gainesville, North Eastern, NorthWestern, John Hopkins, PNNL, UCSB. |
| Start Year | 2008 |