High-throughput low-volume crystallisation facility
Lead Research Organisation:
University of Leeds
Department Name: Institute of Membrane & Systems Biology
Abstract
This is an equipment proposal, to enable ground-breaking research. Almost all of our understanding of how proteins and nucleic acids such as DNA work has come from structural biology. This requires growing crystals of these macromolecules, as in the pioneering work of Max Perutz, who won a Nobel prize in 1962 for solving the structure of the oxygen-carrying protein of the blood, haemoglobin. The hardest things to crystallise are the proteins that sit in the membranes that surround living cells, because they are not soluble in water - but these proteins are the targets for 50% of all drugs. They are also the ones that turn sunlight into energy, conduct nerve impulses and transport nutrients of all kinds into cells.
Over the last ten years, there has been a revolution in methods for crystallising proteins, especially membrane proteins, and our proposal is to equip the University of Leeds, and thus other local universities (Sheffield, Huddersfield, Newcastle and Manchester) with this cutting-edge equipment. The equipment has three components: (1) characterisation equipment (SEC-MALLS, LCP-FRAP), which will help us determine if the protein is likely to be crystallisable in the conditions being used; (2) a crystallisation robot so that we can use 20-50 times less protein than before ("drops" of 20-50 nl, rather than 1 ul) in each crystallisation trial; and (3) robotic imagers both at 4 C and room temperature. As we will be doing tens of thousands of trials, robotic imagers make visualising the experiments much easier than having to look at each experiment one by one under a microscope. In addition, the crystallisation robot can make "lipidic cubic phase" (LCP) drops, which corresponds to squeezing out 50 nl of toothpaste at a time. LCP has in particular revolutionised the crystallisation of membrane proteins but, like toothpaste, it is opaque. Consequently, we are also buying a "SONICC" imager, which will enable us to see very small protein crystals in the opaque LCP.
The post-genomic era has provided unimagined insights into the chemistry and regulatory mechanisms underlying life, and structural biology has been an very important part of this. Despite successes with water-soluble proteins, major challenges remain, particularly for membrane proteins and large mammalian/eukaryotic protein complexes, which this equipment will address. The structural work at the Astbury Centre for Structural Molecular Biology is centred around four major overlapping theme areas: (1) Membrane proteins; (2) large complexes; (3) pathogen-host interactions; and (4) design of small molecules (i.e. drugs).
Examples of projects where we expect breakthroughs are: how do the ion-channels involved in sensing pain, temperature or taste work? How do viruses that contain RNA, like the common cold or smallpox, package the RNA inside themselves? This is required for the virus to be infective. How do large molecular machines, like the vacuolar ATPase, work and how are they regulated? These are important in trypanosomal parasites that cause major diseases in both animals and humans. Can we understand better how some plants resist the toxicity of metals such as aluminium, and can we therefore enhance this ability in major crops? This will help make crops grow better, with less use of fertilisers, in acidic soils. Finally, bacteria that accumulate on surfaces form biofilms - around teeth, around prosthetic implants, on the surfaces of ships, with adverse consequences. Understanding how this happens and preventing it requires understanding the structures of the proteins involved.
Over the last ten years, there has been a revolution in methods for crystallising proteins, especially membrane proteins, and our proposal is to equip the University of Leeds, and thus other local universities (Sheffield, Huddersfield, Newcastle and Manchester) with this cutting-edge equipment. The equipment has three components: (1) characterisation equipment (SEC-MALLS, LCP-FRAP), which will help us determine if the protein is likely to be crystallisable in the conditions being used; (2) a crystallisation robot so that we can use 20-50 times less protein than before ("drops" of 20-50 nl, rather than 1 ul) in each crystallisation trial; and (3) robotic imagers both at 4 C and room temperature. As we will be doing tens of thousands of trials, robotic imagers make visualising the experiments much easier than having to look at each experiment one by one under a microscope. In addition, the crystallisation robot can make "lipidic cubic phase" (LCP) drops, which corresponds to squeezing out 50 nl of toothpaste at a time. LCP has in particular revolutionised the crystallisation of membrane proteins but, like toothpaste, it is opaque. Consequently, we are also buying a "SONICC" imager, which will enable us to see very small protein crystals in the opaque LCP.
The post-genomic era has provided unimagined insights into the chemistry and regulatory mechanisms underlying life, and structural biology has been an very important part of this. Despite successes with water-soluble proteins, major challenges remain, particularly for membrane proteins and large mammalian/eukaryotic protein complexes, which this equipment will address. The structural work at the Astbury Centre for Structural Molecular Biology is centred around four major overlapping theme areas: (1) Membrane proteins; (2) large complexes; (3) pathogen-host interactions; and (4) design of small molecules (i.e. drugs).
Examples of projects where we expect breakthroughs are: how do the ion-channels involved in sensing pain, temperature or taste work? How do viruses that contain RNA, like the common cold or smallpox, package the RNA inside themselves? This is required for the virus to be infective. How do large molecular machines, like the vacuolar ATPase, work and how are they regulated? These are important in trypanosomal parasites that cause major diseases in both animals and humans. Can we understand better how some plants resist the toxicity of metals such as aluminium, and can we therefore enhance this ability in major crops? This will help make crops grow better, with less use of fertilisers, in acidic soils. Finally, bacteria that accumulate on surfaces form biofilms - around teeth, around prosthetic implants, on the surfaces of ships, with adverse consequences. Understanding how this happens and preventing it requires understanding the structures of the proteins involved.
Technical Summary
Our goal is to add a modern crystallisation section to our structural pipeline. We lack the critical equipment components.
The main technical objectives are thus to:
(1) Acquire a size-exclusion chromatography setup with multiangle laser light scattering (MALLS), refractive index and dynamic light scattering detectors. With this, we wil be able to determine parameters critical for crystallisation such as: the absolute molecular mass of the peak on the column as a function of time, the protein:detergent ratio in the peak, and if it is monodisperse or not.
(2) Acquire crystallisation robotics including lipidic cubic phase technology (LCP), which has become an essential component of membrane protein crystallography.
(3) Acquire robotic imaging at 20 and 4 C, so that we can routinely scan 96-well crystallisation plates and deliver those images to internal and external users. This should include a SONICC-TPEF imager, which allows the detection of very small (micron-sized) protein crystals in the opaque LCP matrix.
(4) Acquire a lipidic cubic phase-fluorescence recovery after photobleaching (LCP-FRAP) setup to determine the mobility of proteins in the LCP matrix. Proteins that are not mobile do not crystallise.
These new tools, which form a consistent whole that exists nowhere in the North of England, will eliminate the major bottleneck in our current structure solution pipeline. The improvements will thus both enhance the productivity of current users and increase the number of in-house and external users.
Our scientific goals will be to use the new equipment to characterise and crystallise a variety of high-value targets, including TRP and Kv channels, vacuolar ATPases and pyrophosphatases, nucleoside transporters and RNA-virus protein complexes.
Our milestones will be purchase, delivery and installation, use by internal users, and use by external users. We will have a workshop to introduce users to the new equipment and techniques.
The main technical objectives are thus to:
(1) Acquire a size-exclusion chromatography setup with multiangle laser light scattering (MALLS), refractive index and dynamic light scattering detectors. With this, we wil be able to determine parameters critical for crystallisation such as: the absolute molecular mass of the peak on the column as a function of time, the protein:detergent ratio in the peak, and if it is monodisperse or not.
(2) Acquire crystallisation robotics including lipidic cubic phase technology (LCP), which has become an essential component of membrane protein crystallography.
(3) Acquire robotic imaging at 20 and 4 C, so that we can routinely scan 96-well crystallisation plates and deliver those images to internal and external users. This should include a SONICC-TPEF imager, which allows the detection of very small (micron-sized) protein crystals in the opaque LCP matrix.
(4) Acquire a lipidic cubic phase-fluorescence recovery after photobleaching (LCP-FRAP) setup to determine the mobility of proteins in the LCP matrix. Proteins that are not mobile do not crystallise.
These new tools, which form a consistent whole that exists nowhere in the North of England, will eliminate the major bottleneck in our current structure solution pipeline. The improvements will thus both enhance the productivity of current users and increase the number of in-house and external users.
Our scientific goals will be to use the new equipment to characterise and crystallise a variety of high-value targets, including TRP and Kv channels, vacuolar ATPases and pyrophosphatases, nucleoside transporters and RNA-virus protein complexes.
Our milestones will be purchase, delivery and installation, use by internal users, and use by external users. We will have a workshop to introduce users to the new equipment and techniques.
Planned Impact
This is an equipment grant for enabling technology to complete the structural biology pipeline at the University of Leeds from protein production to x-ray diffraction and structure solution by providing the vital missing intermediate step: modern characterisation, crystallization and imaging equipment. The academic impact is thus on solving breakthrough structures. Who are the other beneficiaries?
SMEs, big pharmaceutical and agribusiness companies will benefit from this research. We already work with a number of such companies, including MedImmune, GlaxoSmithKline, AstraZeneca and Aptamer Solutions, and structures of important agricultural or pharmaceutical targets will be of direct benefit to them as they will provide the basis for design of new small molecules (e.g. antibacterials, antifungals). The research will also lead to better understanding of how proteins work, which is of great importance to SMEs in synthetic biology and in metabolic engineering. We have in the past and will in the future patent our discoveries, so the work will lead to improving the economic competitiveness of the EU in general and the UK in particular. The timeframe for drug development is 5-15 years.
A number of the structures are of relevance for public health and animal welfare, and so for international policy and policy makers. This is particularly true for those like the vacuolar ATPase and pyrophosphatase, which are important in trypanosomal diseases such as sleeping sickness. Trypanosomiasis reduces human and animal productivity across large swathes of sub-Saharan Africa. New approaches and drugs will thus improve the quality of life in the developing world in particular. Some of the work has benefits for government agencies and regulators because it will lead to new ways of determining the effects of food additives and drugs: the effects can be studied on the target molecules, rather than via animal testing. The timeframe for this is the next 5-10 years.
There are three immediate benefits to this proposal. First, the immediate research environment in the North of England benefits hugely, as the complete structural biology pipeline proposed does not exist here. It thus meets the goals of the research councils to coordinate and minimize duplication, and it provides important regional support so that Leeds and the North maintain their traditional strength in structural biology, rather than have it all concentrated within 80 miles of Whitehall.
Second, all of the investigators, and the University of Leeds, are committed to outreach to the local and UK community in a variety of ways: inviting schoolchildren in to the University, having them do summer projects in laboratories, giving talks and radio interviews, and acting as a consultants for outreach efforts aimed at teenagers.
Finally, a major transferrable benefit of all academic research is the people trained during the project. The scientists using the equipment acquired through this grant will acquire professional skills that they can use in research-based biotechnological industry. In addition the University of Leeds has an extensive career development program that will provide transferrable skills. These trained people as they move to other institutions in academia, in government and in industry, will affect the larger society positively in all the ways described above.
SMEs, big pharmaceutical and agribusiness companies will benefit from this research. We already work with a number of such companies, including MedImmune, GlaxoSmithKline, AstraZeneca and Aptamer Solutions, and structures of important agricultural or pharmaceutical targets will be of direct benefit to them as they will provide the basis for design of new small molecules (e.g. antibacterials, antifungals). The research will also lead to better understanding of how proteins work, which is of great importance to SMEs in synthetic biology and in metabolic engineering. We have in the past and will in the future patent our discoveries, so the work will lead to improving the economic competitiveness of the EU in general and the UK in particular. The timeframe for drug development is 5-15 years.
A number of the structures are of relevance for public health and animal welfare, and so for international policy and policy makers. This is particularly true for those like the vacuolar ATPase and pyrophosphatase, which are important in trypanosomal diseases such as sleeping sickness. Trypanosomiasis reduces human and animal productivity across large swathes of sub-Saharan Africa. New approaches and drugs will thus improve the quality of life in the developing world in particular. Some of the work has benefits for government agencies and regulators because it will lead to new ways of determining the effects of food additives and drugs: the effects can be studied on the target molecules, rather than via animal testing. The timeframe for this is the next 5-10 years.
There are three immediate benefits to this proposal. First, the immediate research environment in the North of England benefits hugely, as the complete structural biology pipeline proposed does not exist here. It thus meets the goals of the research councils to coordinate and minimize duplication, and it provides important regional support so that Leeds and the North maintain their traditional strength in structural biology, rather than have it all concentrated within 80 miles of Whitehall.
Second, all of the investigators, and the University of Leeds, are committed to outreach to the local and UK community in a variety of ways: inviting schoolchildren in to the University, having them do summer projects in laboratories, giving talks and radio interviews, and acting as a consultants for outreach efforts aimed at teenagers.
Finally, a major transferrable benefit of all academic research is the people trained during the project. The scientists using the equipment acquired through this grant will acquire professional skills that they can use in research-based biotechnological industry. In addition the University of Leeds has an extensive career development program that will provide transferrable skills. These trained people as they move to other institutions in academia, in government and in industry, will affect the larger society positively in all the ways described above.
Publications
Burslem GM
(2016)
Towards "bionic" proteins: replacement of continuous sequences from HIF-1a with proteomimetics to create functional p300 binding HIF-1a mimics.
in Chemical communications (Cambridge, England)
Burslem GM
(2017)
Hypoxia inducible factor (HIF) as a model for studying inhibition of protein-protein interactions.
in Chemical science
Burgess SG
(2018)
Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic a-helix.
in The EMBO journal
Boakes JC
(2022)
Novel variants provide differential stabilisation of human equilibrative nucleoside transporter 1 states.
in Frontiers in molecular biosciences
Bhattacharjee A
(2015)
The major autoantibody epitope on factor H in atypical hemolytic uremic syndrome is structurally different from its homologous site in factor H-related protein 1, supporting a novel model for induction of autoimmunity in this disease.
in The Journal of biological chemistry
Description | As mentioned under Impact, it is strange to report on the activities of about 30 other laboratories. The grant was for enabling technology, not research. That being said, we can say that we and other groups have used the infrastructure to crystallise new proteins and obtain novel protein structures. Four examples are as follows: 1) The infrastructure underpins x-ray crystallisation and structural biology in the Astbury Centre for Structural and Molecular Biology. As such, it is used by a great number of different groups, and enables graduate students and PDRAs to make progress in their research, as evidence by the papers published. These papers include ones in Plant Cell and Nature Communications. 2) The infrastructure has been instrumental in creating new collaborations, including underpinning the Leeds involvement in two EU Innovative Training Networks, RAMP (funded in 2017) and ViBrANT (funded in 2018). The former is focussed specifically on developing new technologies to crystallise membrane proteins, which the crystallisation robots bought as part of the grant are ideal for. The consortium involves two of the original PIs (Goldman and Pearson); Pearson has now moved to the University of Hamburg, as well as leading players in membrane protein structural biology from inter alia France, Ireland, Sweden, Denmark and two major pharmaceutical companies (Novartis and AstraZeneca) as well as three SMEs. This is a major new research network. 3) New structures of pyrophosphatases that have the potential to lead to drug design against malaria parasites, and published in Nature Communications in 2016; new potential inhibitors have already been designed, including ones that kill malaria parasites at micromolar concentrations. 4) New work has led to extending the molecular recognition achieved by enzymes (work published in PNAS in 2017). this will allow better enzyme design and redesign. 5) New work on binding of adhirons to Fc receptors led to understanding how to bind specific FcRs for therapeutic design (work published in PNAS in 2018). 6) The work has led to new models of how the aurora kinase work: this is important in various cancers. |
Exploitation Route | The research findings have been in the areas of Adhirons, and how they bind to various molecules. These are being developed as potential diagnostic tools and in principle for clinical use. Structures of viral proteins and of proteins from malaria parasites are being used for drug design. Work on proteomimetics may lead to novel protein-like structures that will have the functions of enzymes but without some of the drawbacks (for instance, improved (thermo)stability; not being degraded in the stomach and so on). |
Sectors | Agriculture Food and Drink Chemicals Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
Description | The grant was for enabling technology for all of the structural biology laboratories at the University of Leeds; and the way the question is phrased implies that I should be able to tell what 30 other laboratories have done - not only their research, but further developments. I think we can assume that, from the published papers, the research has been useful in identifying new approaches to drugs and to biotechnology: the standard immediate outputs for protein structures. Another major impact, of course, has been that students have used the infrastructure, and it has helped them graduate and achieve their PhDs. All grants have this as an output. |
First Year Of Impact | 2016 |
Sector | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Impact Types | Societal Economic |
Description | Confidence in Concept Award |
Amount | £65,750 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2018 |
End | 02/2020 |
Description | David Phillips Fellowship |
Amount | £1,274,037 (GBP) |
Funding ID | BB/N019970/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2016 |
End | 10/2021 |
Description | Fellowship for Julie Heggelund |
Amount | £321,000 (GBP) |
Organisation | Research Council of Norway |
Sector | Public |
Country | Norway |
Start | 01/2017 |
End | 12/2019 |
Description | Marie Curie Innovative Training Network |
Amount | € 3,243,300 (EUR) |
Organisation | European Union |
Sector | Public |
Country | European Union (EU) |
Start | 03/2017 |
End | 03/2021 |
Description | Marie Curie Innovative Training Network (ViBrANT) |
Amount | € 4,500,000 (EUR) |
Funding ID | 765042 |
Organisation | European Union |
Sector | Public |
Country | European Union (EU) |
Start | 01/2018 |
End | 12/2022 |
Description | Marie Curie postdoctoral fellowship |
Amount | € 183,000 (EUR) |
Organisation | Marie Sklodowska-Curie Actions |
Sector | Charity/Non Profit |
Country | Global |
Start | 06/2015 |
End | 06/2017 |
Description | Marie Curie postdoctoral fellowship |
Amount | € 183,000 (EUR) |
Organisation | Marie Sklodowska-Curie Actions |
Sector | Charity/Non Profit |
Country | Global |
Start | 08/2016 |
End | 08/2018 |
Description | Marie Curie postdoctoral fellowship |
Amount | € 183,000 (EUR) |
Organisation | Marie Sklodowska-Curie Actions |
Sector | Charity/Non Profit |
Country | Global |
Start | 08/2016 |
End | 08/2018 |
Description | Responsive mode call |
Amount | € 608,000 (EUR) |
Organisation | Academy of Finland |
Sector | Public |
Country | Finland |
Start | 08/2015 |
End | 08/2019 |
Description | Royal Society Wolfson Laboratory Refurbishment Scheme |
Amount | £1,281,000 (GBP) |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2016 |
End | 03/2017 |
Description | University of Leeds graduate student fellowship scheme |
Amount | £45,000 (GBP) |
Organisation | University of Leeds |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2014 |
End | 07/2017 |
Description | Wellcome Trust ISSF |
Amount | £50,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2018 |
End | 08/2019 |
Description | White Rose graduate fellowship scheme |
Amount | £45,000 (GBP) |
Organisation | White Rose University Consortium |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2015 |
End | 07/2018 |
Title | PDB CODES |
Description | These are structures generated by groups who have used the crystallisation robots. The PDB codes are: 5C3F, 5C3G, 5A36, 5A37, 5A38, 5A4B, 5IU1, 5A0O, 5C3F, 5C3G 5A8G, 5A97 5AG2, 4X9Q 4CRZ, 4CS0, 5A0O, 6ELK, 5ELJ, 5EQL, 5ELU, 5LS7, 6EZZ, 6GRR, 6FHK, 5Y17, 5XVZ, 5XY4, 5ZZ1, 6F9I, 6EJN, 5ODS, 5ODT, 5MN2 and 5ML9 |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | not applicable |
URL | http://www.ebi.ac.uk/pdbe/ |
Description | Ace1 transport proteins |
Organisation | University of Leeds |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | provide intellectual input on protein structure solution; advise Marie Curie Fellow |
Collaborator Contribution | Provide mechanistic studies on the Acinetobacter baumannii Ace1 protein, provide protein for crystallography |
Impact | Crystallography, allied with protein production, membrane biology, biophysical and biochemical studies |
Start Year | 2016 |
Description | Collaboration on Fc gamma Receptors |
Organisation | University of Leeds |
Department | University of Leeds Special Collections |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have been responsible for solving the structures of a series of Fcgamma receptors, both mutant and wild-type, examining their complexes, performing SEC-MALLs analysis, and analysing what the structures mean for the interactions of Fcs with their receptors |
Collaborator Contribution | Our partners have been involved in identifying intriguing Fcgamma receptor mutations using genome-wide association studies, in studying the effects of these receptors in cell-based assays, and in developing novel binding partners (adhirons) that can inhibit specific Fcgamma receptors. |
Impact | Robinson, J. I., Baxter, E. W., Owen, R. L., Thomsen, M., Tomlinson, D. C., Waterhouse, M. P., Win, S. J., Nettleship, J. E., Tiede, C., Foster, R. J., Owens, R. J., Fishwick, C. W. G., Harris, S. A., Goldman, A., McPherson, M. J. & Morgan, A. W. Affimer proteins inhibit immune complex binding to Fc?RIIIa with high specificity through competitive and allosteric modes of action. Proc. Natl. Acad. Sci. U S A 115, E72-E81 (2018). |
Start Year | 2016 |
Description | Collaboration on TAAs |
Organisation | European University Viadrina Frankfurt (Oder) |
Country | Germany |
Sector | Academic/University |
PI Contribution | This is part of the ViBrANT Innovative training network on bacterial and viral adhesion proteins. Our role in this collaboration is to solve the structures of different trimeric autotransporter adhesins (TAAs) bound to potential ligands, as the basis for interfering with their function. |
Collaborator Contribution | The partners are involved in producing the TAAs, and in studying their biological and biophysical properties. |
Impact | none yet |
Start Year | 2017 |
Description | Collaboration on TAAs |
Organisation | University of Oslo |
Country | Norway |
Sector | Academic/University |
PI Contribution | This is part of the ViBrANT Innovative training network on bacterial and viral adhesion proteins. Our role in this collaboration is to solve the structures of different trimeric autotransporter adhesins (TAAs) bound to potential ligands, as the basis for interfering with their function. |
Collaborator Contribution | The partners are involved in producing the TAAs, and in studying their biological and biophysical properties. |
Impact | none yet |
Start Year | 2017 |
Description | Collaboration on structure of Kv channels |
Organisation | University of Leeds |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Purification of the Kv1.2 channel from Pichia pastoris for crystallisation |
Collaborator Contribution | Reagents for the project; clones; advice |
Impact | Collaboration is not multidisciplinary. Outcomes: purified protein for crystallisation |
Start Year | 2013 |
Description | Collaboration on the Comatose ABC family D transporter |
Organisation | Rothamsted Research |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Setting up for crystallisation of the comatose protein |
Collaborator Contribution | Production of the comatose protein |
Impact | none so far |
Start Year | 2014 |
Description | Collaboration on the Comatose ABC family D transporter |
Organisation | University of Leeds |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Setting up for crystallisation of the comatose protein |
Collaborator Contribution | Production of the comatose protein |
Impact | none so far |
Start Year | 2014 |
Description | Collaboration with Nankai |
Organisation | Nankai University |
Country | China |
Sector | Academic/University |
PI Contribution | Will provide clones and house a graduate student for the purpose of collaborative research |
Collaborator Contribution | Provides graduate student for two years to perform research on membrane proteins |
Impact | 10.1371/journal.pone.0143010 |
Start Year | 2014 |
Description | Structural studies of mutants of Mhp1 |
Organisation | University of Leeds |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Advice on crystallising the Mhp1 mutants; access to the crystallisation robotics |
Collaborator Contribution | production, purification, structure solution. |
Impact | Initial draft of a manuscript on the Mhp1 mutants |
Start Year | 2014 |
Description | Astbury Conversation 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | The Astbury Conversation is a biennial event that allows researchers and the general public to discuss innovative technologies and techniques in the field of structural biology. The highlight of the event was the talk given by Nobel prize winner Brian Kobilka on GPCRs. As many members of the general public are unfamiliar with this topic we set up a stall to describe GPCR function and why they were worth studying. Various groups including the general public, school, and university students visited this event and engaged in scientific discussions involving drug discovery and the scientific techniques. This increased their awareness on the difficulties of bringing a new drug to market. |
Year(s) Of Engagement Activity | 2018 |
URL | https://astburyconversation.leeds.ac.uk/ehome/index.php?eventid=200183132& |
Description | DiscoveryZone |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | 300 keystage 2 and 3 pupils attend and are engaged in hands-on scientific activities from over 30 different stations. |
Year(s) Of Engagement Activity | 2016,2017,2018,2019 |
URL | http://www.fbs.leeds.ac.uk/outreach/schools/lfos.php |
Description | Participation in a Be Curious, a public outreach event |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | More than 100 members of the public visited the University of Leeds Be Curious open day event, which highlighted the range of science being researched. Our stall was designed to explain cells and membrane proteins to the public and explain how structural studies could be used to create new drugs. |
Year(s) Of Engagement Activity | 2017 |
Description | Participation in open day activities associated with the Astbury Conversation |
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 | Schools |
Results and Impact | 300 members of the general public, including school-children were part of the open sessions at the Astbury conversation. The keynote speaker in 2018 was the Nobelist Brian Kobilka, and in 2020 will be Nobelist Richard Henderson. There was increased interest in the idea of using structural understanding to develop much improved drugs - for instance in the opioid family of drugs. We present a stall of the activities in the laboratory, including hands-on demonstrations |
Year(s) Of Engagement Activity | 2018,2020 |
Description | School visits for crystallisation facility |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | 30 pupils visited the BBSRC crystallisation facility as part of open days. It led to increased interest and enthusiasm for structural biology. |
Year(s) Of Engagement Activity | 2014,2015,2016,2017,2018,2019 |
Description | Student visits for the Baldwin memorial symposium |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | 127 keystone 4 pupils from local schools attended a public lecture by the Nobelist Professor Sir John Walker, FRS, and also were involved in a visit to the laboratories. They had an introduction to scientific techniques, sparking interest in biological research areas. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.fbs.leeds.ac.uk/baldwin/ |