Solution NMR spectroscopy studies of an adrenergic receptor b1AR
Lead Research Organisation:
University of Cambridge
Department Name: Biochemistry
Abstract
Living organisms are made up of a very large quantity of cells. Each of these cells contains machinery that is essential to maintain and develop the life of a particular organism. These cells are surrounded by a waterproof lipid membrane, which encapsulates the mostly aqueous interior of a cell that includes also the essential molecular machinery.
Every process of life both on a large as well as on a small scale involves continuous adaptations to a changing environment. Following such changes and responding to the demands that arise through the activities of the organisms the conditions within the individual cells need to be continuously adjusted. Every cell needs to be supplemented with nutrients for energy and building materials, waste products need to be removed and instructions need to be given for the multitude of different processes to act in a concerted manner. To facilitate these requirements across the impenetrable lipid membrane a large number of proteins are embedded into the cell membrane. These proteins connect the cell exterior with the inside of the cell and are called membrane proteins. A particular group of these proteins is responsible for relaying information in form of control signals across the membrane. The cells are using these proteins as sensors that relay a message from the exterior to the inside of a cell, where a cell is then able to understand what adjustments need to be made. The range of such control signals can be very diverse and there are therefore several hundreds of these sensors making this a particularly important group of membrane proteins. In fact it turns out to be the largest family of proteins in humans. Our work is looking in more details at these proteins, the so-called G protein coupled receptors GPCRs. We are trying to understand how exactly it is that these proteins work and in particular how different external control signals for a given sensor facilitate the different responses on the inside of the cell. Exposure of these proteins on the surface of the cells makes them easily accessible, which is crucial for them to work properly. It makes them also ideal targets for drugs in situations when our body malfunctions and needs drug therapeutic help. Therefore next to the academic interest in understanding how these proteins work there is a large interest from the pharmaceutical industry for the development of newer and better drugs from which our general well being will benefit.
To be able to address such questions typically requires biologists and chemists to zoom in on a molecular level using a range of biophysical techniques, which allow us to see what is happening on an atomic scale. Our lab is using a technique called nuclear magnetic resonance (NMR), which allows us to study these GPCR proteins in a nearly native environment. For the technique to work the GPCR under study is removed from the cell membrane but is still kept surrounded by a very small portion of it. These proteins are extremely unstable and hence very tricky to study. We are concentrating on a particular member of the GPCR family, which has been modified and displays enhanced properties to assist our investigations.
These sensor proteins are considered to be highly mobile and their dynamic nature strongly influences how they function. NMR is an excellent method that can describe which parts of these proteins are flexible. We are particularly interested in studying how the mobility in these proteins changes in the presence of different external signals so that we can correlate these variations with the given responses inside the cell. Most likely our results will allow us to make conclusions that are very general in nature as it is highly likely that other GPCRs will function following a similar way of action. So far GPCRs have been elusive to such studies and our work intends to generate this novel insight.
Every process of life both on a large as well as on a small scale involves continuous adaptations to a changing environment. Following such changes and responding to the demands that arise through the activities of the organisms the conditions within the individual cells need to be continuously adjusted. Every cell needs to be supplemented with nutrients for energy and building materials, waste products need to be removed and instructions need to be given for the multitude of different processes to act in a concerted manner. To facilitate these requirements across the impenetrable lipid membrane a large number of proteins are embedded into the cell membrane. These proteins connect the cell exterior with the inside of the cell and are called membrane proteins. A particular group of these proteins is responsible for relaying information in form of control signals across the membrane. The cells are using these proteins as sensors that relay a message from the exterior to the inside of a cell, where a cell is then able to understand what adjustments need to be made. The range of such control signals can be very diverse and there are therefore several hundreds of these sensors making this a particularly important group of membrane proteins. In fact it turns out to be the largest family of proteins in humans. Our work is looking in more details at these proteins, the so-called G protein coupled receptors GPCRs. We are trying to understand how exactly it is that these proteins work and in particular how different external control signals for a given sensor facilitate the different responses on the inside of the cell. Exposure of these proteins on the surface of the cells makes them easily accessible, which is crucial for them to work properly. It makes them also ideal targets for drugs in situations when our body malfunctions and needs drug therapeutic help. Therefore next to the academic interest in understanding how these proteins work there is a large interest from the pharmaceutical industry for the development of newer and better drugs from which our general well being will benefit.
To be able to address such questions typically requires biologists and chemists to zoom in on a molecular level using a range of biophysical techniques, which allow us to see what is happening on an atomic scale. Our lab is using a technique called nuclear magnetic resonance (NMR), which allows us to study these GPCR proteins in a nearly native environment. For the technique to work the GPCR under study is removed from the cell membrane but is still kept surrounded by a very small portion of it. These proteins are extremely unstable and hence very tricky to study. We are concentrating on a particular member of the GPCR family, which has been modified and displays enhanced properties to assist our investigations.
These sensor proteins are considered to be highly mobile and their dynamic nature strongly influences how they function. NMR is an excellent method that can describe which parts of these proteins are flexible. We are particularly interested in studying how the mobility in these proteins changes in the presence of different external signals so that we can correlate these variations with the given responses inside the cell. Most likely our results will allow us to make conclusions that are very general in nature as it is highly likely that other GPCRs will function following a similar way of action. So far GPCRs have been elusive to such studies and our work intends to generate this novel insight.
Technical Summary
Although crystal structure determination of GPCRs has become increasingly available over the last years, there is a distinct lack of insight on the dynamic nature of these highly mobile signaling proteins. Downstream signal transduction events follow from extracellular ligand-induced interactions that dynamically change the functional state of the receptor. Information on this functional receptor plasticity is not accessible through crystal structure snapshots obtained in often non-native detergent environments. Considering predominantly structure based static arguments therefore is unlikely to reveal all the essential aspects of how GPCRs function. Hence, investigation through complementary techniques that can provide information on receptor dynamics is urgently required. NMR is well suited to provide such information, however, until now the success of extensive NMR studies on GPCRs has been obstructed by the unfavourable properties of these proteins; sample preparation being a major bottleneck for structural studies of GPCRs.
We intend to pursue comprehensive solution NMR studies of a class A GPCR. Our study will concentrate on a conformationally thermostabilized mutant of turkey b1AR which has been extensively used in X-ray crystallography studies and which provides beneficial sample characteristics to enable extensive NMR studies. The receptor is stabilized predominantly in one conformation, which results in superior NMR spectral quality due to improved sample homogeneity. In addition, spin relaxation dispersion techniques can probe the presence of 'invisible' low-populated receptor states and will provide the missing information on the conformational dynamics of the receptor. Using uniform and selective isotope labelled b1AR samples we will utilise this approach to study what effect ligands of different efficacies have on the conformational dynamics of the receptor, which regions of the GPCR are affected and how the changes depend on the type of ligand bound.
We intend to pursue comprehensive solution NMR studies of a class A GPCR. Our study will concentrate on a conformationally thermostabilized mutant of turkey b1AR which has been extensively used in X-ray crystallography studies and which provides beneficial sample characteristics to enable extensive NMR studies. The receptor is stabilized predominantly in one conformation, which results in superior NMR spectral quality due to improved sample homogeneity. In addition, spin relaxation dispersion techniques can probe the presence of 'invisible' low-populated receptor states and will provide the missing information on the conformational dynamics of the receptor. Using uniform and selective isotope labelled b1AR samples we will utilise this approach to study what effect ligands of different efficacies have on the conformational dynamics of the receptor, which regions of the GPCR are affected and how the changes depend on the type of ligand bound.
Planned Impact
Our work concentrates on understanding how G protein-coupled receptors (GPCRs) function. This remains one of the most important and challenging questions in biology, not only from a mechanistic perspective but also for general human health. GPCRs form the largest family of proteins in humans and regulate most aspects of normal physiology as membrane embedded signalling molecules. Obtaining insight into dynamics and structure of GPCRs is essential for the mechanistic understanding of their activation and forms a vital asset for future drug development. The function of these proteins is modulated by their dynamic nature and NMR is the only method, which is able to provide information on conformational dynamics at atomic resolution. We will use our extensive expertise in the study of membrane proteins by NMR to characterize the dynamic behaviour of GPCRs. This work will be immediately beneficial to academic/industrial labs, both nationally and internationally, as it will provide a proof of principle how NMR spectroscopy can reveal the plasticity of GPCRs and how signalling is altered by different ligands. Data will be generated through our work that correlates ligand properties and their efficacies with the conformational sampling of the receptor. This information will be highly complementary to existing structural data and benefit the wider signalling community and drug design. Our approach will be transferrable to other stabilized receptors. Using stabilising lipid environments we anticipate even wildtype proteins to become accessible eventually. Technical improvements through our work will also benefit the research community studying membrane proteins by NMR. Staff working on this project will immediately and directly benefit, as they will develop/acquire skills in protein work, NMR and data analysis leading to mechanistic understanding. This will improve their employment prospects in both academic and industrial environments. Training expert post-doctoral scientists in these skills will also be highly beneficial to future employers. By adding to the trained pool of researchers in the UK we will increase the economic competitiveness of the country by strengthening its position in the global academic and pharmaceutical market. Our previous work on large helical membrane proteins and the research pursued here make our lab one of the leading experts in the field in the UK and worldwide. Our expertise in the study of such proteins will provide a strong asset for the UK GPCR community who can benefit from our expertise and through collaborative efforts will be able to explore mechanistic features of other receptors. Our work will significantly add to the knowledge base of how GPCRs work and how downstream signalling responses can be influenced. It is becoming increasingly clear that next to G-proteins GPCRs interact also with a range of other proteins that result in non-G-protein related signalling processes. This harbours enormous potential for biotech and pharmaceutical industry to expand drug therapeutic interventions through the design of ligands that influence or bias specific signal transduction. In the medium term (2-10 years) pharmaceutical industry will be able to rely on NMR derived information to gauge the mode of action of these proteins. This information will be vital to guide the development of drugs. Effective remedies can only be developed from an understanding of the underlying molecular principles of the biology involved. Increased mechanistic understanding will lead to improved as well as new drug types, further expanding an already multi-billion pound market. This will increase revenue in the UK, secure employment in the future and generate wealth and prosperity. As GPCRs affect many areas of the human physiology, a multitude of novel therapeutic approaches will be able to counter the effects aberrant signalling has, helping large portions of the population. This will improve the general health of our society.
Organisations
- University of Cambridge (Lead Research Organisation)
- National Cheng Kung University (Collaboration)
- University of Leipzig (Collaboration)
- Leibniz Association (Collaboration)
- University of Gothenburg (Collaboration)
- Novartis Institutes for BioMedical Research (NIBR) (Collaboration)
- National Tsing Hua University (Taiwan) (Collaboration)
- Academia Sinica (Collaboration)
- Novartis (Switzerland) (Project Partner)
People |
ORCID iD |
Daniel Nietlispach (Principal Investigator) |
Publications
Bostock M
(2016)
Application of random coherence order selection in gradient-enhanced multidimensional NMR
in Journal of Physics: Conference Series
Bostock M
(2018)
Compressed sensing: Reconstruction of non-uniformly sampled multidimensional NMR data
in Concepts in Magnetic Resonance Part A
Bostock M
(2017)
Fast NMR Data Acquisition - Beyond the Fourier Transform
Bostock MJ
(2017)
Improving resolution in multidimensional NMR using random quadrature detection with compressed sensing reconstruction.
in Journal of biomolecular NMR
Bostock MJ
(2019)
The role of NMR spectroscopy in mapping the conformational landscape of GPCRs.
in Current opinion in structural biology
Chien CH
(2017)
An Adaptable Phospholipid Membrane Mimetic System for Solution NMR Studies of Membrane Proteins.
in Journal of the American Chemical Society
Crick DJ
(2015)
Integral membrane protein structure determination using pseudocontact shifts.
in Journal of biomolecular NMR
Description | Using a thermostabilized form of the G-protein-coupled receptor turkey b1 adrenergic receptor we are investigating the dynamics for receptor activation. Using 1H,13C heteronuclear NMR spectroscopy based on selectively labelled b1AR samples we are exploring the level of conformational dynamics involved and how these are affected upon ligand binding. A range of different ligands varying from agonists to inverse agonists in their efficacies are being explored and functional states of the receptor are also studied in the presence of G-protein mimetics. At the current stage of the investigations it is clear that the employed technology is highly suited to investigate the functional activation of b1AR. Previous problems with protein expression have been overcome and we are able now to produce high quality spectra of 13C methyl labeled methionine samples on a routine basis. Using side chain methyl groups of methionine residues has the benefit that the monitored resonances in the spectra directly report on changes in side chain interactions rather than being the result of indirect effects as when using signals from the backbone moiety. While our results are complementary to the insight provided by X-ray crystallography studies we are able to see that receptors are dynamic and adopt different conformations also under conditions where well defined single receptor conformations are being obtained through X-ray studies. In other words binding of individual ligands does not result in well defined single receptor states but modulates the populations of different states. This is even the case for stabilized receptors that have been generated based on binding to a very particular ligand. This is interesting and underpins the role of the inherent mobility of these receptors in order to modulate the amount and lifetime of states that lead to the differential downstream signalling responses. Our investigations are ongoing. Our initial studies show a clear correlation between activity state of the receptor and its overall mobility. In general, agonist bound b1AR is most mobile while apo form or partial agonist bound receptor states are less mobile. In the ternary complex, once bound to G protein mimetics the receptor is much less dynamic. We describe clear correlations between efficacy of ligands bound to the receptor and the structure of adapted by the latter. Focusing our investigations on ternary complexes between receptor, agonist and G-protein mimetic nanobodies we find that partial agonism leads to variable interaction of the receptor with its cytoplasmic G-protein mimetic. In fact, the receptor seems to be exchanging between two states - a less active, and a fully active state. This provides the initial basis for a structural explanation of partial agonism where different efficacy of ligands leads to varying ability of the receptor to interact with G-protein. |
Exploitation Route | Our work will generate further insight into GPCR functioning and how ligand activation works. This is highly relevant for the pharmaceutical industry, basic understanding of protein signalling and for drug design. |
Sectors | Pharmaceuticals and Medical Biotechnology |
URL | http://www.nature.com/articles/s41467-017-02008-y |
Description | G-protein-coupled receptors (GPCRs) are membrane embedded molecules that communicate instructions from outside the cell to the cell interior by dynamically adapting different conformational states upon interaction with a stimulus. Depending on the receptor involved, this stimulus can be in the form of light, small organic molecules, ions, peptides, proteins etc. and result in the activation of the plasma-membrane embedded receptor. Adaptation of an active state conformation by the receptor results then in downstream signalling events via a large range of signalling cascades. GPCRs are controlling a wide range of physiological processes and through their malfunction are responsible for a multitude of diseases. Their location in the cell-surrounding membrane makes them readily accessible targets for drugs and today around 40% of commercially available drugs are targeting GPCRs. However, current drugs only target a small portion of existing receptors so that this area harbours vast therapeutic potential for the future. Many existing drugs show dramatic side effects or require fine-tuning of their response. Understanding how these receptors function under closely native conditions therefore is key for the development of new drug-based therapeutical interventions and the improvement of existing ones. Our first round of results have been published in the literature and our findings are being disseminated at international conferences, via collaborations and through interactions with academic research, research institutes, pharmaceutical and small biotech industry, which emphasizes the key role of our current research. Key areas our work is impacting on can be summarised as following: 1. Development of a rational understanding of how GPCRs work contributes to the ability to develop new drugs and improve existing therapies. Pharmaceutical industry and biotech sector benefit from our study and this will lead to increased research activity. This will have a positive economical impact for the UK, lead to economical growth, will secure employment in this sector and maintain the UK at the forefront of international research. 2. New drug therapies will benefit the general health of the public, increase living standards and support the health sector with the required tools to address diseases in the future. 3. Training of academic staff working on the funded project will guarantee the future generation of academic researcher in the UK. This is taking place both at postdoctoral level and graduate research student level and through collaboration with researchers at industry level. 4. Pursuing highly topical research will generally increase the profile of the UK and maintain its role as a world class research environment. This will guarantee to maintain international involvement in the future e.g. in the form of collaboration, and by attracting international top researchers. |
First Year Of Impact | 2017 |
Sector | Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | A dynamic view of GPCR-G protein complexes: insight into partial agonism and G protein selectivity |
Amount | £680,470 (GBP) |
Funding ID | BB/W020718/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 11/2022 |
End | 10/2025 |
Description | Expression of G protein-coupled receptors in E.coli. |
Amount | £63,000 (GBP) |
Funding ID | RG53842 |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2010 |
End | 10/2013 |
Description | Expression of the b1-adrenergic receptor using Pichia pastoris. |
Amount | £83,000 (GBP) |
Funding ID | RG53842 |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2011 |
End | 10/2014 |
Description | MRC Industrial CASE |
Amount | £95,327 (GBP) |
Funding ID | MR/L014254/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2014 |
End | 10/2018 |
Description | Studies of helical membrane proteins using NMR spectroscopy |
Amount | £62,000 (GBP) |
Funding ID | RG53842 |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2009 |
End | 04/2012 |
Title | Compressed Sensing data reconstruction methodology |
Description | Development of data processing methodology to accelerate NMR spectroscopy. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | The developed methodology enables the study of more complex biological studies using NMR spectroscopy. |
Title | NMR data processing software for the reconstruction of undersampled data |
Description | 3D and 4D NMR data takes a long time to record. We show that a combination of sparse data sampling combined with the use of Compressed Sensing processing can lead to large time savings or lead to higher sensitivity and resolution per unit time. This boosts the performance of NMR equipment and becomes an indispensable tool for the study of large molecular weight biomolecules. The processing routines are now available as a standalone platform independent package. |
Type Of Material | Computer model/algorithm |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Software for NMR data processing to allow reconstruction of non-uniformly sampled data. The algorithm will enter the annual contest for data processing of NUS NMR data and will be one of the leading softwares. |
Description | Cell free expression of G-protein-coupled receptors |
Organisation | University of Gothenburg |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Cell free expression of membrane proteins using a system developed by collaborator. Refolding of receptors. NMR spectroscopy |
Collaborator Contribution | The partner has given us expression constructs and has provided know-how. |
Impact | -Invited presenations: Leipzig talk 2013 Biophysics meeting 2014 ETH talk 2014 Luebeck talk 2014 CCPN meeting 2014 Keystone meeting 2014 Gotingen talk 2014 Petnica School 2014 India talk 2014 Astex talk 2014 Cambridge NMR conference 2014 |
Start Year | 2012 |
Description | Cell free expression of membrane proteins |
Organisation | Academia Sinica |
Department | Institute of Biological Chemistry |
Country | Taiwan, Province of China |
Sector | Academic/University |
PI Contribution | Expression of transmembrane domain of EGFR |
Collaborator Contribution | Expression of kinase domain of EGFR with varying C-terminal length constructs |
Impact | No outputs yet. |
Start Year | 2016 |
Description | Drug development appraoches to b1 adrenergic receptors |
Organisation | National Cheng Kung University |
Country | Taiwan, Province of China |
Sector | Academic/University |
PI Contribution | We are studying the suitability of small molecules to influence binding of b1AR |
Collaborator Contribution | The partner is providing small molecules targeting b1AR |
Impact | There are no outputs yet. |
Start Year | 2017 |
Description | Investigating the light activation mechanism of the signal receptor pSRII |
Organisation | Academia Sinica |
Department | Institute of Astronomy and Astrophysics |
Country | Taiwan, Province of China |
Sector | Academic/University |
PI Contribution | We are making 2H,15N and 15N isotopically labeled protein samples for NMR studies of the protein in detergent micelles. In addition we are preparing samples with the receptor reconstituted into lipid nanoparticles. |
Collaborator Contribution | Our collaborators have conducted initial investigations into the kinetics of the light cycle and on steady state light excitation. These investigations are key for our ongoing light activation study by NMR, where we are exciting the protein in-situ via laser light activation. Our collaborators have optimized techniques to improve the light excitation. THis is a key step of our investigations as the concentrated protein samples absorb a lot of the light and it has proven difficult to excite sufficient receptor without bleaching the ground state. |
Impact | This study will see some dramatic progress during 2018. Subsequently we will publish the outcomes of our measurements. |
Start Year | 2016 |
Description | Investigating the light activation mechanism of the signal receptor pSRII |
Organisation | National Tsing Hua University (Taiwan) |
Country | Taiwan, Province of China |
Sector | Academic/University |
PI Contribution | We are making 2H,15N and 15N isotopically labeled protein samples for NMR studies of the protein in detergent micelles. In addition we are preparing samples with the receptor reconstituted into lipid nanoparticles. |
Collaborator Contribution | Our collaborators have conducted initial investigations into the kinetics of the light cycle and on steady state light excitation. These investigations are key for our ongoing light activation study by NMR, where we are exciting the protein in-situ via laser light activation. Our collaborators have optimized techniques to improve the light excitation. THis is a key step of our investigations as the concentrated protein samples absorb a lot of the light and it has proven difficult to excite sufficient receptor without bleaching the ground state. |
Impact | This study will see some dramatic progress during 2018. Subsequently we will publish the outcomes of our measurements. |
Start Year | 2016 |
Description | Solid state NMR spectroscopy of G-protein-coupled receptors |
Organisation | Leibniz Association |
Country | Germany |
Sector | Academic/University |
PI Contribution | Sample preparation for solid state NMR spectroscopy. Detergent and lipid reconstituted receptor samples are prepared and sent to Berlin for NMR spectroscopy. |
Collaborator Contribution | Recording of solid state NMR spectra |
Impact | No outputs yet. |
Start Year | 2018 |
Description | Studying molecular changes during GPCR receptor activation |
Organisation | Novartis Institutes for BioMedical Research (NIBR) |
Country | United States |
Sector | Private |
PI Contribution | Expression of isotopically labelled GPCR receptors, purification and preparation of NMR samples. NMR spectroscopy studies of GPCRs. |
Collaborator Contribution | Baculovirus expression of GPCR in isotopically labelled form. |
Impact | -publication: doi:10.1038/nmeth.2691 -Invited talks: Leipzig talk 2013 Biophysics meeting 2014 ETH talk 2014 Luebeck talk 2014 CCPN meeting 2014 Keystone meeting 2014 Gotingen talk 2014 Petnica School 2014 India talk 2014 Astex talk 2014 Cambridge NMR conference 2014 |
Start Year | 2012 |
Description | solution and solid state study of GPCR dynamics |
Organisation | University of Leipzig |
Country | Germany |
Sector | Academic/University |
PI Contribution | Solution NMR spectroscopy on the Y2 GPCR |
Collaborator Contribution | Protein expression and purification, refolding and sample preparation for NMR. Solid state measurements. |
Impact | -Invited talks at meetings: Leipzig talk 2013 Biophysics meeting 2014 ETH talk 2014 Luebeck talk 2014 CCPN meeting 2014 Keystone meeting 2014 Gotingen talk 2014 Petnica School 2014 India talk 2014 Astex talk 2014 Cambridge NMR conference 2014 |
Start Year | 2011 |
Title | NMR data processing: Compressed sensing to improve NMR performance |
Description | 3D and 4D NMR data takes a long time to record. We show that a combination of sparse data sampling combined with the use of Compressed Sensing processing can lead to large time savings or lead to higher sensitivity and resolution per unit time. This boosts the performance of NMR equipment and becomes an indispensable tool for the study of large molecular weight biomolecules. The processing algorithms are now available as a GUI supported platform independent software package. The code allows FT, CS, ME reconstruction of fully or NUS sampled data, including RQD. |
Type Of Technology | New/Improved Technique/Technology |
Year Produced | 2017 |
Impact | Software for NMR data reconstruction. |
Description | Astex talk 2014 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker at Astex Pharmaceuticals, Cambridge UK title of talk: Structure and function of 7-helical membrane proteins investigated by NMR spectroscopy 1st July 2014 Stimulated interest in membrane protein work. Following my presentation we established a work collaboration. |
Year(s) Of Engagement Activity | 2014 |
Description | Biophysics meeting 2014 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | keynote/invited speaker |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | British biophysical society conference 2014 New frontiers in biophysics University of Warwick Invited speaker title of talk: Funtional studies from 7TN receptors: insight from solution NMR spectroscopy 9-11th July 2014 Triggered stimulating discussions at the end of the session. Approached for collaboration with UK academics |
Year(s) Of Engagement Activity | 2014 |
Description | CCPN meeting 2012 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Type Of Presentation | poster presentation |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | Poster presentation Bostock M. J., Holland, D. J., Nietlispach D. (2012). Compressed sensing reconstruction of undersampled NOESY spectra of large membrane proteins. Collaborative Computing Project for NMR (CCPN) conference, September 2012, Scarborough Interest in our software development. Other research groups would like to try the program. |
Year(s) Of Engagement Activity | 2012 |
Description | CCPN meeting 2014 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Type Of Presentation | poster presentation |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | 2 posters presented: -Bostock M. J. and Nietlispach D. (2014). The influence of sampling schedules on compressed sensing reconstructions of NMR spectra. -Activation dependent conformational changes of the b1 adrenergic receptor visualized by methionine NMR spectroscopy S Berndt; D Crick; B Shrestha; T Warne; W Jahnke; C Tate; D Nietlispach CCPN conference 2014, Scarborough UK 1-3 September 2014 Some members from the audience are interested in our activities and would like to try the software developed in our lab (unfunded activity). |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.ccpn.ac.uk/events/ccpn-conference-scarborough-2014 |
Description | Cambridge NMR Conference 2014 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Type Of Presentation | workshop facilitator |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Co-organiser of the meeting: including organisation and co-responsibility for putting scientific program together NMR in structural biology Co-organiser 10-11 April 2014 University of Cambridge, Department of Chemistry Received very positive echo from audience on the quality of the scientific program that had been put together. Showed that short meetings can be excellent medium for scientific exchange. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www-keeler.ch.cam.ac.uk/NMRDG/ |
Description | Collaborative Computing Project for NMR (CCPN) Conference 2021 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Research presentation on G-protein coupled receptors and their study using NMR spectroscopy with emphasis on dynamic aspects of these molecules. The talk stood in the context of several presentations given on complementary topics that were the highlight of this annual conference. The conference is an important fixture in the calendar of the UK structural biology and NMR community but has also strong international attendance. The 3 day conference took place as a hybrid event (in person and online talks). |
Year(s) Of Engagement Activity | 2021 |
URL | https://ccpn.ac.uk/past-conferences/2021-ambleside/ |
Description | Conference attendance and presentation of poster |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Presentation of latest research results |
Year(s) Of Engagement Activity | 2016 |
Description | Conference participation at UK CCPN meeting, the annual UK biomolecular NMR meeting |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | First joint meeting between structural biology and molecular simulation community in view of a multidisciplinary approach towards macromolecular structure determination. |
Year(s) Of Engagement Activity | 2016 |
Description | Course intructor at NMR practical course on biological NMR spectroscopy |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Workshop instructor on a one week long course. This course was previously funded by EMBO and is not funded by alternative sources. |
Year(s) Of Engagement Activity | 2018 |
Description | ETH talk 2014 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Invited Seminar speaker ETH Zurich, Switzerland title of talk: Structure and function of 7-helical membrane proteins studied by NMR spectroscopy 18 March 2014 talk triggered long discussion and many questions Undergraduate students found talk a very useful introduction into the subject |
Year(s) Of Engagement Activity | 2014 |
Description | Gottingen talk 2014 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited speaker. Title: Functional studies of 7tm receptors: insight from solution NMR spectroscopy SFB 803 Symposium, Georg-August University, Gottingen 29.9-1.10 2014 Gottingen Germany Was approached for collaborations following talk |
Year(s) Of Engagement Activity | 2014 |
Description | India talk 2014 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Invited speaker: Structure and Function of 7-Helical Membrane Proteins Studied by NMR Spectroscopy NMR meets biology 21-27 February 2014 Goa, India Talk stimulated great interest. Title: Structure and Function of 7-Helical Membrane Proteins Studied by NMR Spectroscopy Intensified collaboration with reasearch group at University of Leipzig |
Year(s) Of Engagement Activity | 2014 |
Description | Instructor/Teacher on EMBO coure on NMR spectroscopy of biological macromolecules |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Teaching about best practice in the use of NMR spectroscopy in structural biology |
Year(s) Of Engagement Activity | 2016 |
Description | Invited seminar speaker, Academia Sinica, Taipei, Taiwan |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Delivered talk |
Year(s) Of Engagement Activity | 2018 |
Description | Invited seminar talk speaker, University Vienna, Vienna Biocenter, Austria |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Delivered talk followed by discussion |
Year(s) Of Engagement Activity | 2018 |
Description | Invited speaker, Leibniz Forschungsinstitut fuer molekulare Pharmakologie, Berlin Germany |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Delivered talk and developed collaborative work plan |
Year(s) Of Engagement Activity | 2018 |
Description | Invited speaker, National Institute of Health, Bethesda Maryland USA |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Delivered talk followed by extensive discussion |
Year(s) Of Engagement Activity | 2018 |
Description | Invited speaker, University of Kent, School of Biosciences, Canterbury UK |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Delivered talk followed by discussion |
Year(s) Of Engagement Activity | 2018 |
Description | Keystone meeting 2014 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Type Of Presentation | paper presentation |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presented poster: G-protein-coupled receptors: structural dynamics and functional implications Poster presentation (Sandra Berndt): Activation dependent conformational changes of the b1 adrenergic receptor visualized by methionine NMR spectroscopy S Berndt; D Crick; B Shrestha; T Warne; W Jahnke; C Tate; D Nietlispach Keystone Symposia Conference Z1 30 March - 4 April 2014 Snowbird Resort, Snowbird Utah Interest in collaboration from people talking to us during poster session. |
Year(s) Of Engagement Activity | 2014 |
Description | Leipzig talk 2013 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Institute seminar talk University of Leipzig title of talk: Insight from NMR spectroscopy on functional studies of 7TM receptors: a progress report 29 September 2013 Talk resulted in further discussion that led to ongoing collaboration (University of Leipzig, Prof Dr D. Huster) |
Year(s) Of Engagement Activity | 2013 |
Description | Luebeck meeting 2014 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | keynote/invited speaker |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker: Annual meeting of the German Biophysical society (DGFB) 14-17 September, Lubeck, Germany title of talk: Functional studies of 7TM receptors: insight from solution NMR spectroscopy Raise interest in topics that can be addressed by NMR |
Year(s) Of Engagement Activity | 2014 |
Description | NMR studies of a-helical membrane proteins |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited speaker, oral presentation 1h. Seminar talk. State of the art information on structure determination of membrane proteins. no actual impacts realised to date |
Year(s) Of Engagement Activity | 2011 |
Description | Petnica School 2014 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Undergraduate students |
Results and Impact | Teaching undergraduate students Petnica School of Bioanalytical Chemistry (Sandra) Talk: Understanding G protein coupled receptors using NMR spectroscopy 1-6 October 2014 Petnica Science Center, Serbia Increase interest in topic presented |
Year(s) Of Engagement Activity | 2014 |
Description | Renewal of research exchange as a basis of intensifying collaboration between Taiwan and UK Universities |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation on biomedical studies that can be addressed through NMR spectroscopy. The meeting led to fostering contacts with Director of MOST (Ministry of Science and Technology) in Taiwan, which as a consequence will be planning a visit to University of Cambridge in 2018. Likely this will lead to increased activities between MOST funded streams via London office of MOST with the intention to intensify research exchange between Universities. |
Year(s) Of Engagement Activity | 2017 |
Description | Structure determination of helical membrane proteins by NMR spectroscopy in solution |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | keynote/invited speaker |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited speaker, oral presentation: 7-TM Membrane proteins can now be studied by NMR as we have successfully demonstrated. no actual impacts realised to date |
Year(s) Of Engagement Activity | 2011 |
Description | Workshop on NMR in biological sciences |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | International workshop on NMR in biomedical sciences. Participated as workshop instructor and lecturer |
Year(s) Of Engagement Activity | 2017 |
Description | Workshop participation, RRR workshop, University of Kyoto, Japan |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Workshop on modern data processing methods geared towards NMR spectroscopy applications on biological systems |
Year(s) Of Engagement Activity | 2015 |