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.

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.

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.

Publications

10 25 50
 
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 International panel member reviewing the Taiwan protein project TPP.
Geographic Reach Asia 
Policy Influence Type Participation in a advisory committee
 
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 10/2010 
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 10/2011 
End 10/2014
 
Description MRC Industrial CASE
Amount £95,327 (GBP)
Funding ID MR/L014254/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2014 
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 04/2009 
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 Public 
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 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