NSF Materials World Network: Heterogeneous Nucleation on Nanoporous Substrates

Lead Research Organisation: Imperial College London
Department Name: Surgery and Cancer

Abstract

The proposed research effort will support an international collaboration between the Chayen group at Imperial College, London (IC), specializing in protein crystallization and the Erlebacher group at Johns Hopkins University, Baltimore (JHU), which specializes in the synthesis and surface modification of nanoporous metals. By marrying these specializations, a fundamental study of heterogeneous crystal nucleation on nanoporous substrates will be efficiently pursued. The collaboration is structured with significant exchange of students and junior personnel; ultimately, the JHU team will develop in-house skills in solution-phase crystallization, and the IC group will learn materials synthesis techniques for fabricating nanoporous metals and nanoporous metal composites, leading to advances in crystallization generally. Fundamentally, our proposed research considers a new approach to thinking about the heterogeneous nucleation of macromolecular species. In traditional heterogeneous nucleation theory, nucleation rates are controlled by the relative interfacial energies between the solvent, substrate, and nucleus. Here, we will tailor the substrate to expose not just one uniform surface to the solution, but instead to expose a statistically relevant distribution of three-dimensionally oriented nucleation sites. Modifications of nucleation theory to explore this idea is an important part of the proposed work and is required for applying the technique generally.A detailed study of the nucleation rate of macromolecules over porous substrates will be performed using a new substrate material / nanoporous gold Nanoporous gold is a random, uniform, mesoporous material whose mean pore size can be varied from 3-50 nm using simple chemistry. Its surface is also easily chemically modified, and all these features together make it uniquely perfect for this kind of study.The results of this research will yield new understanding of the fundamentals of heterogeneous nucleation, with general applicability to protein and colloidal crystallization. Furthermore, the international collaboration will help to build international networks in nucleation theory and experiment, bridging the disciplines of thin film metallurgy and solution phase crystallization.
 
Description Protein crystals are vital for facilitating the design of new medicines and for industrial applications. Obtaing high quality crystals is a bottleneck to progress, thus there is a continuous quest for developing efficient methods for producing crystals. It was found that materials with pores (cavities) of similar size to those of protein molecules are effective in inducing nucleation and thus formation of protein crystals. This project set out to test nanoporous gold as a nucleant for protein crystals and to test a theory and experiments to investigate the effectiveness of nanoporous substrates as nucleation inducing materials. Nanoporous gold was applied as a substrate (nucleant) for the heterogeneous nucleation of five proteins. The results demonstrate that nanoporous gold is effective as a nucleant and that surface chemistry and surface area effects play the dominant role in nucleation when using these nanoporous nucleants. These results have practical applications for obtaining useful crystals as this knowledge will help guide future studies of nanoporous nucleants for protein crystallization by highlighting the importance of tailoring favorable energetic interactions between the protein and the substrate.
Exploitation Route The nanoporous gold has potential use to SMEs and to biotechnology and pharmaceutical companies interested in structure determination of proteins and other biological macromolecules. Nanoporous gold can be commerciallised as a product for protein crystal formation. There are several companies selling kits and products to aid protein crystallisation to laboratories in academia and to industry and Pharma.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description PhD Stundenship
Amount £65,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 11/2011 
End 11/2016
 
Description Co-chair of European Crystallography Association Special Interest Group (SIG 6) on Instrumentation and Experimental Techniques 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Co-chair of European Crystallography Association Special Interest Group (SIG 6) on Instrumentation and Experimental Techniques This position enables decisions on speakers and sessions at the annual European Crystallography Meetings. Awarding Body - European Crystallography Association, Name of Scheme - Special Interest Groups

Decisions concerning the European Crystallography
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015
 
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 Executive Board member, International Organization for Biological Crystallization 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Executive Board member of the International Organization for Biological Crystallization The impact of this position is having influence on scientific and management decisions of the organisation. Awarding Body - International Organization for Biological Crystallization, Name of Scheme - Learned International Organisation

decision making
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015
 
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 Expert in Protein Crystallization 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Invited speaker/expert at the European Commission Directorate General for Research to discuss the Vision for 2020 and the future of Systems Biology in Europe to identify the state of the art and challenges/future needs of biological crystallization in the context of integrating proteomics, interactomics and structural biology via systems biology approaches. The expert panel was gathered to advise the European Commission of research themes in the area of structural biology and systems biology. Awarding Body - European Commission, Name of Scheme - Vision 2020

Giving advice and reccommendations
Year(s) Of Engagement Activity 2010
 
Description Invited lecture at Brandeis University 
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 Guest lecture on crystallization and Nucleantion of Proteins.

continued collabration
Year(s) Of Engagement Activity 2013
 
Description Invited lecture at European Crystallography Meeting 2015 
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 afterwards

requests for collaboration
Year(s) Of Engagement Activity 2015
 
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 lecture at the Institut Laue Langevin, Grenoble, France 
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 Invited lecture at the Institut Laue Langevin, Grenoble, France.

Discussion how to combine knowledge
Year(s) Of Engagement Activity 2013
 
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 Member of Evaluation Board of European Commission projects 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Member of a Board of experts to evaluate applications for using infrastructure platforms provided within the 7th Framework Program of the European Commission which combine research, networking and service of cutting edge technologies in contemporary structural biology Evaluation of applications for using infrastructure platforms provided within the 7th Framework Program of the European Commission which combine research, networking and service of cutting edge technologies in contemporary structural biology. Awarding Body - European Commission, Name of Scheme - infrastructure platforms for Structiral Biology

This activity informed the choice of the best projects
Year(s) Of Engagement Activity 2010,2011,2012,2013
 
Description Member of Review Panel, Brookhaven National Laboratory Synchrotron Source, USA 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Member of Review Panel selecting projects for analysis using the Brookhaven National Laboratory Synchrotron Source, USA The panel revies the applications and decided which projects should be recommended to go ahead.. Awarding Body - Brookhaven National Laboratory, Name of Scheme - Synchron radiation source allocations

Decision on what projects to give the go ahead
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013,2014,2015
 
Description Member of the L'Oréal-UNESCO Jury Panel for the UK and Ireland For Women In Science National Fellowships 2012. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Member of the L'Oréal-UNESCO Jury Panel for the UK and Ireland For Women In Science National Fellowships 2012. The panel of 8 people decided on the awards of the prestigious L'Oreal Unesco Fellowships. Awarding Body - L'Oréal-UNESCO, Name of Scheme - Fellowships

The committee sealected the people to receive the L'oReal award
Year(s) Of Engagement Activity 2012
 
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 Outreach 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact talk sparked questions and discussion afterwards

Many questions and comments from the public
Year(s) Of Engagement Activity 2014
 
Description Outreach to schools 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Schools
Results and Impact Showing year 10 pupils around crystallization and structural biology laboratories.

Raised interest of school children in the subject
Year(s) Of Engagement Activity 2012
 
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 Speaker to the public at Soapbox Science event at Southbank, London 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact speaker at Soapbox Science event at Southbank organised by L'Oreal, the Royal Society and the Zoological Society of London aimed at showcasing UK women in science, inspiring the next generation of scientists and making science fun and accessible.

12 senior women scientists in different fields of science stood in the wind on soapboxes and spoke to the passers by. Young and old people listened with interest and asked questions.

successful otreach to the public
Year(s) Of Engagement Activity 2011
URL http://blogs.independent.co.uk/2011/07/27/women-in-science-crystals-leading-to-discovery-of-new-medi...