Smart Materials: Development of Protein Recognition Polymers as Novel Surfaces for Protein Crystallisation.
Lead Research Organisation:
Imperial College London
Department Name: Surgery and Cancer
Abstract
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Organisations
People |
ORCID iD |
| Naomi Chayen (Principal Investigator) |
Publications
Chayen
(2010)
Macromolecular Crystallization and Crystal Perfection
Govada L
(2017)
Smart materials for increasing the success of protein crystallization
in Acta Crystallographica Section A Foundations and Advances
Khurshid S
(2014)
Porous nucleating agents for protein crystallization.
in Nature protocols
Khurshid S
(2015)
Automating the application of smart materials for protein crystallization.
in Acta crystallographica. Section D, Biological crystallography
Naomi Chayen
(2010)
Protein Crystallization using Molecularly Imprinted Polymers
Reddy SM
(2012)
Protein crystallization and biosensor applications of hydrogel-based molecularly imprinted polymers.
in Biomacromolecules
Saridakis E
(2013)
Imprinted polymers assisting protein crystallization.
in Trends in biotechnology
Saridakis E
(2011)
Protein crystallization facilitated by molecularly imprinted polymers.
in Proceedings of the National Academy of Sciences of the United States of America
| Description | In this project we set out to test a new idea for obtaining protein crystals which are required to facilitate rational drug design. In collaboration with a chemist/material scientist we succeeded in developing a totally unique means of nucleating protein crystals, by designing Molecularly Imprinted Polymers (MIPs) also referred to as "smart materials" for this purpose. The idea was to find a material that would specifically attract protein molecules to come together and form a crystal. MIPs are polymers formed in the presence of a molecule that is extracted afterwards, leaving complementary cavities behind. The cavities retain a memory of the molecule in the polymer and exhibit highly selective rebinding of the given molecule. In this study, MIPs were imprinted with protein molecules. The fingerprint of the protein created on the polymer enables it to serve as an ideal template for its crystal formation. We have shown that MIPs are effective in both the screening and optimisation stages of crystallization. MIP-containing screening trials (in a widely used commercial screen) yielded promising hits for three proteins that had not produced useful crystals to date. No hits were obtained in the absence of MIPs or in the presence of traditional nucleants, meaning that without MIPs these important hits would have been missed. An additional key discovery was that better crystals could be obtained in the presence of MIPs at the optimization stage. Nine proteins out of ten tested produced higher quality crystals (as measured by X-ray diffraction), notably of an HIV protein complex (4.2 Å compared to 9 Å previously). The findings went beyond our expectations: when embarking on the MIP experiments we expected that each MIP would work exclusively on its cognate protein and that it would be necessary to make a MIP for each protein to be crystallized. In practice, our results showed that a MIP imprinted with one protein could also be successfully used for other, size-compatible proteins. This is very important in the case of difficult to crystallize proteins, which are usually too scarce in supply for imprinting and would therefore benefit from the use of a related MIP. The results of this study open up a new scope for protein crystallization corroborating our hypothesis that by harnessing proteins as templates, MIPs become effective nucleation-inducing substrates. |
| Exploitation Route | The finding has been patented, the patent has been granted and a commercial product called 'Chayen Reddy MIP' is commercilaised and sold to pharmaceutical companies and academia by Imperial Innovations. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| URL | http://www.imperialinnovations.co.uk/license/available-technologies/chayen-reddy-mip/ |
| Description | The findings were patented (patent was granted) and a commercial product called 'Chayen Reddy MIP' is sold to pharmaceutical companies and academia by Imperial Innovations. The research and its resulting technnique was covered by numerous websites e.g the engineer, Physorg.com and many others thereby reaching a wide audience in both academia and industry. Contribution Method: It proved the concept of the idea The discovery of MIPs and validation of their use for inducing the formation of protein crystals was highlighted in a New and Views article in Nature Chemistry. Having the research and its outcome chosen to be highlighted by a high impact journal such as Nature Chemistry ensures wide distribution of the research and its usesfulness. Beneficiaries: The readers, The inventors, ademia and industry Contribution Method: The research proved the hypothesis that MIPs can act as nucleating agents for protein crystallization. The research and its resulting new technique was covered as a Research News Highlight in the journal Nature Methods entitled 'Taming Crystals' Whimsy'. The results were highlighted by a high impact scientific journal. Beneficiaries: The Authors, the Colleges and ultimately the users of the technique that was developed by the research Contribution Method: By proving the concept of a new idea The scientific paper was reviewed by Faculty 1000 for recommended reading. The scientific paper was reviewed by Faculty 1000 a presitigeous academic body for recommended reading. Beneficiaries: The academic readership Contribution Method: The research proved the concept of the hypotheis that MIPs will act as efficient nucleating agents for the formation of protein crystals Smart materials prod proteins to form crystalline gems. Write up as Cutting -edge science and picture of the day in the NewScientist a journal read by the public as well as by scientists. Beneficiaries: The Authors, the Colleges and the public readership Contribution Method: It underpinned the technique |
| First Year Of Impact | 2015 |
| Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Title | Chayen Reddy MIP |
| Description | A new tool for inducing the growth of protein crystals |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | Obtaining crystasls that could not be obtaned before |
| URL | http://www.imperialinnovations.co.uk/license/available-technologies/chayen-reddy-mip/ |
| Title | PROTEIN CRYSTALLIZATION USING MOLECULARLY IMPRINTED POLYMERS |
| Description | The invention relates to a method comprising: providing a molecularly imprinted polymer imprinted with a first peptide or protein;exposing said molecularly imprinted polymer to a supersaturated solution of a second peptide or protein;and forming a nucleus of, and/or growing a crystal of, said second peptide or protein on said molecularly imprinted polymer. |
| IP Reference | WO2010139972 |
| Protection | Patent application published |
| Year Protection Granted | 2010 |
| Licensed | Yes |
| Impact | A commercial product was launched in 2015 and is selling to Academia and industry such as pharmaceutical companies |
| Title | Protein crystallisation technique |
| Description | A method of growing a protein crystal, or forming a nucleus of a protein, comprises providing a molecularly imprinted polymer imprinted with a first peptide or protein, and exposing said molecularly imprinted polymer to a supersaturated solution of a second peptide or protein; and forming a nucleus of, and/or growing a crystal of, said second peptide or protein on said molecularly imprinted polymer. The first and second protein or peptide may be the same or different. The method may be adapted to identify appropriate crystallisation conditions for a given protein or peptide. Crystallisation of lysozyme, trypsin, thaumatin and catalase are exemplified, using a molecularly imprinted polymer produced from acrylamide. |
| IP Reference | GB2470744 |
| Protection | Patent granted |
| Year Protection Granted | 2010 |
| Licensed | Yes |
| Impact | A product called Chayen Reddy MIP was launched in 2015 and is being sold to academia and industry |
| Description | Crystal World Exhibition at The Royal Society |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Crystal World Exhibition at The Royal Society. While crystals are important substances in many scientific disciplines, their powerful visual presence and metaphorical associations have also intrigued artists and philosophers over many centuries. Although a crystal appears 'lifeless' or dead, it can also suggest life; it has grown from a solution or compond. The artists in this exhibition have been inspired in diferent ways by these complex, transient chemical processes, and by their many aesthetic possibilities. Increased interest from the public in science |
| Year(s) Of Engagement Activity | 2011 |
| URL | http://royalsociety.org/events/2011/crystal-world/ |
| Description | Exhibitor at Imperial Science Festival 2017 |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Hundreds of people came over a period of 2 days to our booth where we showed them why and how to crystallise proteins. This sparked questions and interest from people of all ages and resulted in invitations for further outreach activities. |
| Year(s) Of Engagement Activity | 2015,2016,2017 |
| Description | Interview by the London Press Service |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Interview by the London Press Service. successful outreach |
| Year(s) Of Engagement Activity | 2011 |
| Description | Interview on the MIPs discovery |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Interview on Labtube on the MIPs discovery. Dissemination to other scientists and the public |
| Year(s) Of Engagement Activity | 2011 |
| Description | Invited lecture at Interantional conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | over 200 people came to the lecture which sparked questions and discussions |
| Year(s) Of Engagement Activity | 2016 |
| Description | Invited lecture at Princeton |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | nearly 100 people attended the lecture and I am getting further invitations to speak as a result and approaches to collaborate |
| Year(s) Of Engagement Activity | 2016 |
| Description | Invited talk at European Crystallography Meeting 2015 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | talk sparked questions and discussion afterwards People asked if they can visit my lab |
| Year(s) Of Engagement Activity | 2015 |
| Description | Keynote lecture |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | over 200 people came to the lecture |
| Year(s) Of Engagement Activity | 2016 |
| Description | Keynote lecture at Crytsallisation conferebce Leeds Centre for Crytasllisation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | talk sparked questions and discussion afterwards requests for Collaboration |
| Year(s) Of Engagement Activity | 2013 |
| Description | New Scientist Live |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | This was a big outreach event in the Excel Centre in London where people aged 5 to 90 came and asked questions. Hundreds of people came and spoke to us. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Pleanry Lecture at European Crystal Growthg Conference in Bologna |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | talk sparked questions and discussion and resulted in collabrations continued and new collaborations |
| Year(s) Of Engagement Activity | 2015 |
| Description | Plenary Lecture at international conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a plenary lecture at an international conference which sparked new scientific collaborations |
| Year(s) Of Engagement Activity | 2017 |
| Description | Plenary talk European Crystal Growth Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | talk sparked questions and discussion afterwards Many people asked to collaborate with me |
| Year(s) Of Engagement Activity | 2015 |
| Description | Press release |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | 'Smart materials' that make proteins form crystals to boost research into new drugs. A Press release on the discovery and validation of the use of MIPs for crystallization was distrubted widely to the media worldwide Increased interest in the subject |
| Year(s) Of Engagement Activity | 2011 |