Imaging cholesterol metabolic flux and transport underlying brain function
Lead Research Organisation:
Swansea University
Department Name: Institute of Life Science Medical School
Abstract
Cholesterol in the central nervous system is separated from the rest of the body by the blood brain barrier. Disturbances in the synthesis, transport or metabolism of cholesterol in the central nervous system are associated with severe neurological and cognitive defects. Although the level of cholesterol in adult brain is at a steady-state there is a continuous turnover with an exquisite balance between de novo synthesis and metabolism. Brain cells synthesise cholesterol throughout life. Mounting evidence suggest that not only is the steady-state concentration of cholesterol important, but that cholesterol precursors and metabolites are also critical for effective brain activity, including learning, memory and motor function. Therefore, a continuous flow of metabolites through the cholesterol synthesis and metabolic pathways is essential to maintain brain function and measuring the spatial flux of metabolites in these pathways will provide further insight into the involvement of cholesterol in proper brain function. How the turnover of cholesterol differs in distinct brain regions and varies with age also affecting brain function is unclear. Furthermore, it is not known if local de novo cholesterol biosynthesis and generation of cholesterol-related molecules is essential for adult neurogenesis, as is the case in the embryo. In this project we will develop "next generation" mass spectrometry imaging technologies to answer these quandaries. Results from this study will be particularly important with the growing use of the statin class of drugs as inhibitors of cholesterol biosynthesis.
Technical Summary
To visualise molecules of the cholesterol pathways in brain according to location and age we will develop "next gerneration" mass spectrometry imaging (MSI) technology. While the detection of a biomolecule in a tissue can be made by MS analysis of a tissue homogenate, all spatial information is lost. To maintain spatial information MSI techniques have been developed where the analytes are ionised by MALDI directly from the tissue surface and an image recorded by rastering of the ionisation beam relative to the sample stage. A major limitation of MSI is that molecules which are in low abundance, or are poorly ionised, are discriminated against. This limitation can be overcome by the use of derivatisation chemistry, where a specific chemical property of the target analyte is exploited to enhance ionisation of the analyte.
Sterols including oxysterols are mainly neutral molecules which ionise poorly and are mostly present in low abundance in biological samples. We will develop on-tissue enzyme-assisted derivatisation for MSI of sterols, where a hydroxy group on a sterol is specifically converted by an enzyme (either cholesterol oxidase for 3beta-hydroxy groups or 3alpha-HSD for 3alpha-hydroxy groups) to a 3-oxo group which is then reacted with a hydrazine reagent carrying a positive charge e.g. Girard P (GP) reagent, to give the sterol a net positive charge and make it very favourable for MS analysis by MALDI or ESI. This method provides specificity and sensitivity revealing many molecules otherwise invisible to MS analysis. For MALDI-MSI we will first apply enzyme to the tissue surface using a sprayer/spotter and after a suitable time period apply GP reagent then matrix. MALDI-MSI will be achieved on a Synapt G2 MS utilising ion-mobility for gas-phase separations. Liquid Extraction for Surface Analysis (LESA) will be performed on similarly treated tissue but in the absence of matrix utilising an Orbitrap for ESI-MSn analysis, with or without prior LC separation.
Sterols including oxysterols are mainly neutral molecules which ionise poorly and are mostly present in low abundance in biological samples. We will develop on-tissue enzyme-assisted derivatisation for MSI of sterols, where a hydroxy group on a sterol is specifically converted by an enzyme (either cholesterol oxidase for 3beta-hydroxy groups or 3alpha-HSD for 3alpha-hydroxy groups) to a 3-oxo group which is then reacted with a hydrazine reagent carrying a positive charge e.g. Girard P (GP) reagent, to give the sterol a net positive charge and make it very favourable for MS analysis by MALDI or ESI. This method provides specificity and sensitivity revealing many molecules otherwise invisible to MS analysis. For MALDI-MSI we will first apply enzyme to the tissue surface using a sprayer/spotter and after a suitable time period apply GP reagent then matrix. MALDI-MSI will be achieved on a Synapt G2 MS utilising ion-mobility for gas-phase separations. Liquid Extraction for Surface Analysis (LESA) will be performed on similarly treated tissue but in the absence of matrix utilising an Orbitrap for ESI-MSn analysis, with or without prior LC separation.
Planned Impact
As cholesterol is implicated in various neurological disorders the proposed research has the potential to generate considerable public interest and social impact. Importantly, statins are widely prescribed as inhibitors of cholesterol biosynthesis in order to reduce the risk of coronary heart disease. However, their effect on brain function and what if any effects they have on neurodegeneration have still to be uncovered. Significantly, following our publication that 24S,25-epoxycholesterol is important for dopaminergic neurogenesis we received a number of queries from the general public questioning the potential danger of taking statins. Much more research into the involvement of cholesterol metabolism in healthy brain function is still required. In the long term, the proposed research will contribute to future guidance to the NHS on the prescription of statins.
A new technology will be developed in this project aimed at visualising molecules in tissues using mass spectrometry imaging (MSI). No molecule, whatever its abundance, can be detected by mass spectrometry if it cannot be ionised. Hence the key element of this proposal is to enhance the ionisation of otherwise invisible molecules by enzyme-assisted chemical derivatisation allowing their observation by MSI. We will exemplify the developed technology in brain in the study of cholesterol precursors and metabolites, which are important for neurogenesis and neuronal survival and whose biosynthesis is crucial for memory and learning. The methods developed will be equally applicable to other classes of molecules and in other tissues. The techniques developed will be of further interest to the pharmaceutical industry as it will enable drug molecules and their metabolites to be imaged in tissue providing information about their local bioavailability.
The beneficiaries of this research will include neuroscientists studying cognition, neurodegeneration or autoimmune disease, three areas where oxysterols (oxidised forms of cholesterol) are important. A follow-on impact will be to the pharmaceutical industry in the development of new drug targets. A small clinical trial is already underway trying to limit the biosynthesis of the neurotoxic oxysterol 3b-HCA. Interpretation of trial results will be facilitated by a better understanding of where this oxysterol and its precursors are synthesised in healthy brain.
Other than colour chromatography, mass spectrometry imaging is perhaps the most visually appealing of all analytical techniques. By colour coding molecular abundance, a digital mass spectrum can be converted to a colour image depicting molecular abundance and location in a tissue. This has great benefits for the public engagement in science, particularly to children.
A final important impact of this project will be the broad education it will give to the employed PDRA, who will become educated in sterol analysis and MSI from two of the leader groups in Europe. In fact both groups will benefit significantly from the proposal as the expertise of the two groups will be shared and most importantly exchanged.
A new technology will be developed in this project aimed at visualising molecules in tissues using mass spectrometry imaging (MSI). No molecule, whatever its abundance, can be detected by mass spectrometry if it cannot be ionised. Hence the key element of this proposal is to enhance the ionisation of otherwise invisible molecules by enzyme-assisted chemical derivatisation allowing their observation by MSI. We will exemplify the developed technology in brain in the study of cholesterol precursors and metabolites, which are important for neurogenesis and neuronal survival and whose biosynthesis is crucial for memory and learning. The methods developed will be equally applicable to other classes of molecules and in other tissues. The techniques developed will be of further interest to the pharmaceutical industry as it will enable drug molecules and their metabolites to be imaged in tissue providing information about their local bioavailability.
The beneficiaries of this research will include neuroscientists studying cognition, neurodegeneration or autoimmune disease, three areas where oxysterols (oxidised forms of cholesterol) are important. A follow-on impact will be to the pharmaceutical industry in the development of new drug targets. A small clinical trial is already underway trying to limit the biosynthesis of the neurotoxic oxysterol 3b-HCA. Interpretation of trial results will be facilitated by a better understanding of where this oxysterol and its precursors are synthesised in healthy brain.
Other than colour chromatography, mass spectrometry imaging is perhaps the most visually appealing of all analytical techniques. By colour coding molecular abundance, a digital mass spectrum can be converted to a colour image depicting molecular abundance and location in a tissue. This has great benefits for the public engagement in science, particularly to children.
A final important impact of this project will be the broad education it will give to the employed PDRA, who will become educated in sterol analysis and MSI from two of the leader groups in Europe. In fact both groups will benefit significantly from the proposal as the expertise of the two groups will be shared and most importantly exchanged.
Organisations
- Swansea University (Lead Research Organisation)
- University Hospital Regensburg (Collaboration)
- University of Oslo (Collaboration)
- University of Basel (Collaboration)
- University of Regensburg (Collaboration)
- Case Western Reserve University (Collaboration)
- Karolinska Institute (Collaboration)
- Athens Medical Center (Collaboration)
- University of Southern Denmark (Collaboration)
- University of Clermont Auvergne (Collaboration)
- University of California - San Diego School of Medicine (Collaboration)
- Oregon Health and Science University (Collaboration)
- Cardiff University (Collaboration)
- Rothamsted Research (Collaboration)
- Washington University School of Medicine (Collaboration)
- Biotechnology and Biological Sciences Research Council (BBSRC) (Collaboration)
- University of Illinois at Chicago (Collaboration)
- University of Franche-Comté (Collaboration)
- Babraham Institute (Collaboration)
- Novartis (Collaboration)
- SHEFFIELD HALLAM UNIVERSITY (Collaboration)
- University of Houston (Collaboration)
- Nebraska Medical Center (Collaboration)
- Université Catholique de Louvain (Collaboration)
- University Hospital Zürich (Collaboration)
- Luxembourg Institute of Science and Technology (Collaboration)
- University of Toulouse (Collaboration)
- Medical University of Graz (Collaboration)
- University of Pardubice (Collaboration)
- University of Queensland (Collaboration)
- Minerva Foundation Institute for Medical Research (Collaboration)
- UNIVERSITY OF EDINBURGH (Collaboration)
- University of Leuven (Collaboration)
- University of Texas Southwestern Medical Center (Collaboration)
Publications
Abdel-Khalik J
(2021)
Bile acid biosynthesis in Smith-Lemli-Opitz syndrome bypassing cholesterol: Potential importance of pathway intermediates.
in The Journal of steroid biochemistry and molecular biology
Angelini R
(2021)
Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging.
in Analytical chemistry
Baloni P
(2020)
Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease.
in Cell reports. Medicine
Crick PJ
(2019)
Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse.
in The Journal of steroid biochemistry and molecular biology
Dickson A
(2023)
HSD3B1 is an oxysterol 3ß-hydroxysteroid dehydrogenase in human placenta.
in Open biology
Dickson AL
(2022)
Identification of unusual oxysterols biosynthesised in human pregnancy by charge-tagging and liquid chromatography - mass spectrometry.
in Frontiers in endocrinology
Griffiths WJ
(2017)
Cholesterolomics: An update.
in Analytical biochemistry
| Description | The idea of on-tissue derivatisation combined with liquid extraction for surface analysis (LESA) and liquid chromatography (LC) linked with mass spectrometry imaging (MSI) has been validated for the analysis of cholesterol, its precursors and its metabolites in mouse brain. We have been able to investigate how the levels of cholesterol and its precursors and metabolites vary in different regions of mouse brain. The major cholesterol metabolite 24S-hydroxycholesterol is found to be most abundant in the striatum and thalamus and least abundant in cerebellum. On the other hand, the neuroprotective cholesterol-derived acid, 3ß,7a-dihydroxycholestenoic acid, is most abundant in the grey matter of the cerebellum, although being at least a factor of ten less abundant that 24S-hydroxycholesterol. 24S,25-Epoxycholesterol is biosynthesised from cholesterol precursors and like 24S-hydroxycholesterol is abundant in thalamus. 24S,25-Epoxycholesterol is a potent ligand towards the liver X receptor, the beta form of which is highly expressed in brain, and important in the neurogenesis of dopaminergic neurons. By analysing brain tissue from the Cyp46a1 knock-out mouse (the enzyme CYP46A1 oxidises cholesterol to 24S-hydroxycholesterol) we were able to confirm the almost complete absence of 24S-hydroxycholesterol in brain of this mouse, but instead identify low levels of its isomers, 12a-, 20S-, 24R- and 25-hydroxycholesterol and of the acid 3ß,7a-dihydroxycholestenoic acid. 20S-Hydroxycholesterol is an elusive metabolite being an important agonist towards the hedgehog signalling process defining stem cell fate. We have now published this data and described the technology in PNAS doi: 10.1073/pnas.1917421117. A limitation of LESA is the spatial resolution of the process (0.3 - 0.4 mm diameter spot). To achieve improved resolution we have exploited on-tissue derivatisation with MALDI (matrix-assisted laser desorption/ionisation)-MSI giving spot diameters of 0.05 - 0.02 mm. This has proved successful to image highly abundant cholesterol in mouse brain doi: https://doi.org/10.1101/2020.11.06.369447. As a consequence of this award we have built new research collaborations with Universities and Research Institutes in the SWBio Doctoral Training Partnership. As part of this DTP we are providing training in specialist mass spectrometry imaging technology to increase research capability across the partnership. |
| Exploitation Route | The next steps will be to (A) use the developed methodology to investigate human brain and see how the distribution of different cholesterol metabolites vary between health and disease and (B) create a mouse brain atlas. The methodology will be valuable to monitor cholesterol biosynthesis and metabolism in mouse models of disease. CYP46A1-gene therapy is a potential treatment for a number of neurodegenerative diseases, our methodology can be used to monitor the direct biochemical outcome of this gene therapy in mouse models of neurodegenerative disease. It is likely that our technology will be taken forward with the pharmaceutical and diagnostics industries. |
| Sectors | Agriculture, Food and Drink,Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| URL | https://www.swansea.ac.uk/press-office/news-events/news/2020/05/researchers-develop-new-method-to-map-cholesterol-metabolism-in-brain.php |
| Description | We have developed a method for locating cholesterol, its precursors and metabolites in minute amounts of brain tissue. The method utilises the LESA PLUS system from Advion Ltd. We have demonstrated how this system can be utilised for tissue analysis at spot size of <0.4 mm. We are working with a diagnostics company to exploit our technology further. Using AP-MALDI supplied by KR Analytical Ltd we have reduced the spot size to <0.01 mm for cholesterol analysis. These developments will contribute to the economic competitiveness of UK companies supplying the instrumentation. |
| First Year Of Impact | 2020 |
| Sector | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | Introducing the Lipidomics Minimal Reporting Checklist |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Contribution to new or improved professional practice |
| URL | https://lipidomicssociety.org/interest_groups/lipidomics-standards-initiative-lsi/ |
| Description | A 3D Neurosterol Atlas of Mouse Brain |
| Amount | £450,711 (GBP) |
| Funding ID | BB/T018542/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2020 |
| End | 12/2023 |
| Description | BRAIN unit - Swansea Neurology |
| Amount | £79,443 (GBP) |
| Organisation | Health and Care Research Wales |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2020 |
| End | 03/2025 |
| Description | MS Society Research Grant Award |
| Amount | £93,333 (GBP) |
| Funding ID | 94 |
| Organisation | Multiple Sclerosis Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2019 |
| End | 03/2022 |
| Description | Mass Spectrometry Based Lipidomics and Metabolomics to Drive Bioscience Discovery |
| Amount | £748,381 (GBP) |
| Funding ID | BB/S019588/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2019 |
| End | 06/2020 |
| Description | Purchase of equipment: The SunCollect System for MALDI imaging sample preparation |
| Amount | £24,500 (GBP) |
| Funding ID | MA/KW/5554/19 |
| Organisation | Government of Wales |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2022 |
| End | 03/2022 |
| Description | Spatial Cholesterol Metabolism: A Mass Spectrometer for Better Diagnosis and Understanding of Disease |
| Amount | £799,419 (GBP) |
| Funding ID | MC_PC_MR/X012387/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2022 |
| End | 03/2023 |
| Title | EADSA-LESA-LC-MSI |
| Description | We have developed a novel technology for mass spectrometry imaging (MSI) of cholesterol, its precursors and metabolites (i.e. sterols) in tissue samples. We perform on-tissue derivatisation, which we call Enzyme-Assisted Derivatisation for Sterol Analysis (EADSA), to specifically target sterols in tissue, we then extract them from small tissue areas (0.3 - 0.4 mm diameter) by Liquid Extraction for Surface Analysis (LESA), separate isomers by liquid-chromatography (LC) and analyse the separated sterols by mass spectrometry (MS). By repeatedly performing extractions and LC-MS over the entire tissue surface we are able to reconstruct an image for each sterol present. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | Using this methodology we are able to define the regions of maximum cholesterol turnover in mouse brain. |
| Title | EADSA-MALDI-MSI |
| Description | We have developed on-tissue derivatisation to enhance the MALDI-mass spectrometry imaging of cholesterol at high spatial resolution. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | The high sensitivity of the method means that many more analysis can be carried out on a single animal reducing animal usage. |
| URL | https://pubs.acs.org/doi/10.1021/acs.analchem.0c05399 |
| Title | Localization of Sterols and Oxysterols in Mouse Brain Reveals Distinct Spatial Cholesterol Metabolism |
| Description | The data presented (DOI 10.17605/OSF.IO/VUD84) facilitates data sharing associated with the manuscript "Localization of Sterols and Oxysterols in Mouse Brain Reveals Distinct Spatial Cholesterol Metabolism" (doi.org/10.1073/pnas.1917421117). The data is presented in Excel, Prism and SPSS files. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | The data set has allowed others to search the data for correlations not reported in the primary publication. This will reduce replicate on animals experiments performed by others. |
| URL | https://osf.io/vud84/ |
| Title | MALDI-MSI - Cholesterol in Mouse Brain |
| Description | The data deposited is MALDI-MSI data in imzML format to accompany the manuscript doi: https://doi.org/10.1101/2020.11.06.369447 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | The availability of the MALDI-MSI dataset will allow searching by others for features not investigated in the primary publication. |
| URL | https://osf.io/39sj7/ |
| Title | Pregnancy Sterols |
| Description | Mass spectrometry raw data from the study of pregnancy sterols described in DOI: 10.3389/fendo.2022.1031013 and doi: https://doi.org/10.1101/2022.04.01.486576 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | Catalyst for new collaborations. |
| URL | https://osf.io/egncz/ |
| Description | Bjorkhem |
| Organisation | Karolinska Institute |
| Country | Sweden |
| Sector | Academic/University |
| PI Contribution | We provide expertise in LC-MS analysis of sterols. |
| Collaborator Contribution | Our partner provides transgenic mouse material, human plasma and CSF. |
| Impact | doi: 10.1194/jlr.P048603 doi: 10.1172/JCI68506 doi: 10.1016/j.jsbmb.2016.03.018 doi: 10.1016/j.biochi.2018.07.016 doi: 10.1074/jbc.RA118.005639 doi: 10.1016/j.jsbmb.2019.03.025 doi: 10.1016/j.jsbmb.2019.105475 doi: 10.1016/j.jsbmb.2020.105794 |
| Start Year | 2007 |
| Description | Cardiff Brain |
| Organisation | Cardiff University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have analysed brain tissue from transgenic animals. |
| Collaborator Contribution | Our partners have provided brain tissue from transgenic animals. |
| Impact | This collaboration has resulted in multiple grant applications. |
| Start Year | 2020 |
| Description | Cardiff LipidMaps |
| Organisation | Babraham Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Expert input on sterol biochemistry. |
| Collaborator Contribution | Expert input on lipid biochemistry |
| Impact | doi: 10.3389/fendo.2020.591819 doi: 10.1194/jlr.S120001025 |
| Start Year | 2017 |
| Description | Cardiff LipidMaps |
| Organisation | Cardiff University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Expert input on sterol biochemistry. |
| Collaborator Contribution | Expert input on lipid biochemistry |
| Impact | doi: 10.3389/fendo.2020.591819 doi: 10.1194/jlr.S120001025 |
| Start Year | 2017 |
| Description | Cardiff LipidMaps |
| Organisation | University of California - San Diego School of Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Expert input on sterol biochemistry. |
| Collaborator Contribution | Expert input on lipid biochemistry |
| Impact | doi: 10.3389/fendo.2020.591819 doi: 10.1194/jlr.S120001025 |
| Start Year | 2017 |
| Description | Case Western Reserve University |
| Organisation | Case Western Reserve University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Analysis of brain tissue from transgenic mouse |
| Collaborator Contribution | Provision of transgenic mouse material |
| Impact | DOI: 10.1073/pnas.1917421117 |
| Start Year | 2018 |
| Description | ENOR |
| Organisation | Catholic University of Louvain |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | ENOR |
| Organisation | Minerva Foundation Institute for Medical Research |
| Country | Finland |
| Sector | Private |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | ENOR |
| Organisation | Novartis |
| Country | Global |
| Sector | Private |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | ENOR |
| Organisation | University Hospital Regensburg |
| Country | Germany |
| Sector | Hospitals |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | ENOR |
| Organisation | University of Basel |
| Country | Switzerland |
| Sector | Academic/University |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | ENOR |
| Organisation | University of Clermont Auvergne |
| Country | France |
| Sector | Academic/University |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | ENOR |
| Organisation | University of Edinburgh |
| Department | Queen's Medical Research Institute Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | ENOR |
| Organisation | University of Franche-Comté |
| Country | France |
| Sector | Academic/University |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | ENOR |
| Organisation | University of Oslo |
| Country | Norway |
| Sector | Academic/University |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | ENOR |
| Organisation | University of Toulouse |
| Country | France |
| Sector | Academic/University |
| PI Contribution | expertise, intellectual input, access to equipment |
| Collaborator Contribution | Access to biological materials |
| Impact | doi: 10.1016/j.jsbmb.2019.03.02 doi: 10.1016/j.biochi.2018.07.016 |
| Start Year | 2010 |
| Description | Edinburgh Imaging |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have provided expertise in enzyme assisted derivatisation for sterol analysis and in liquid extraction for surface analysis (LESA)-mass spectrometry imaging (MSI). |
| Collaborator Contribution | Our partners have provided expertise in on-tissue derivatisation and access to mouse tissue. |
| Impact | The collaboration has resulted in the successful joint grant application "A 3D Neurosterol Atlas of Mouse Brain" BB/T018542/1. |
| Start Year | 2019 |
| Description | Karolinska |
| Organisation | Karolinska Institute |
| Country | Sweden |
| Sector | Academic/University |
| PI Contribution | We have brought essential data and insight to the collaboration. We are bringing new technology |
| Collaborator Contribution | They have brought essential data and insight to the collaboration. Our partners are bringing transgenic animal material and expertise to the collaboration. |
| Impact | This is a multidisciplinary collaboration between neuroscientists and clinical chemists at Karolinska Institute and analytical scientists in Swansea. doi: 10.3390/biom9040149 doi: 10.1074/jbc.RA118.005639 doi: 10.1016/j.bbalip.2018.11.006 doi: 10.1172/JCI68506 doi: 10.1038/nchembio.1156 WO2014132052A2 EP3044192B1 |
| Start Year | 2006 |
| Description | Lipidomics Standards Initiative |
| Organisation | Babraham Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Intellectual input to the Lipidomics Standards Initiative. |
| Collaborator Contribution | Intellectual input. |
| Impact | doi.org/10.1038/s42255-019-0094-z |
| Start Year | 2018 |
| Description | Lipidomics Standards Initiative |
| Organisation | Cardiff University |
| Department | School of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Intellectual input to the Lipidomics Standards Initiative. |
| Collaborator Contribution | Intellectual input. |
| Impact | doi.org/10.1038/s42255-019-0094-z |
| Start Year | 2018 |
| Description | Lipidomics Standards Initiative |
| Organisation | Medical University of Graz |
| Country | Austria |
| Sector | Academic/University |
| PI Contribution | Intellectual input to the Lipidomics Standards Initiative. |
| Collaborator Contribution | Intellectual input. |
| Impact | doi.org/10.1038/s42255-019-0094-z |
| Start Year | 2018 |
| Description | Lipidomics Standards Initiative |
| Organisation | University of Pardubice |
| Country | Czech Republic |
| Sector | Academic/University |
| PI Contribution | Intellectual input to the Lipidomics Standards Initiative. |
| Collaborator Contribution | Intellectual input. |
| Impact | doi.org/10.1038/s42255-019-0094-z |
| Start Year | 2018 |
| Description | Lipidomics Standards Initiative |
| Organisation | University of Regensburg |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Intellectual input to the Lipidomics Standards Initiative. |
| Collaborator Contribution | Intellectual input. |
| Impact | doi.org/10.1038/s42255-019-0094-z |
| Start Year | 2018 |
| Description | Lipidomics Standards Initiative |
| Organisation | University of Southern Denmark |
| Country | Denmark |
| Sector | Academic/University |
| PI Contribution | Intellectual input to the Lipidomics Standards Initiative. |
| Collaborator Contribution | Intellectual input. |
| Impact | doi.org/10.1038/s42255-019-0094-z |
| Start Year | 2018 |
| Description | Lipidomics Standards Initiative |
| Organisation | University of Texas Southwestern Medical Center |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Intellectual input to the Lipidomics Standards Initiative. |
| Collaborator Contribution | Intellectual input. |
| Impact | doi.org/10.1038/s42255-019-0094-z |
| Start Year | 2018 |
| Description | Luxembourg Institute of Science and Technology, |
| Organisation | Luxembourg Institute of Science and Technology |
| Department | GP Lippmann Public Research Institute (CRP) |
| Country | Luxembourg |
| Sector | Academic/University |
| PI Contribution | We contributed expertise in cholesterol biochemistry and analysis. |
| Collaborator Contribution | Our partner provided access to data, equipment and facilities. |
| Impact | https://doi.org/10.1101/2020.11.06.369447 |
| Start Year | 2019 |
| Description | Mass Spectrometry Imaging |
| Organisation | Sheffield Hallam University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Provide expertise in sterol/steroid analysis and derivatisation protocols. |
| Collaborator Contribution | Provide expertise in MALDI imaging |
| Impact | DOI: 10.1073/pnas.1917421117 |
| Start Year | 2016 |
| Description | Oregon Health and Sciences University |
| Organisation | Oregon Health and Science University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have provided expertise in oxysterol and sterol analysis. |
| Collaborator Contribution | Our partners have provided tissue and fluids for analysis. |
| Impact | DOI: 10.1016/j.biochi.2018.06.020 |
| Start Year | 2017 |
| Description | Peroxisome |
| Organisation | University of Leuven |
| Department | Zoological Institute |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | Expertise in sterol and oxysterol analysis |
| Collaborator Contribution | Expertise in biochemistry of the peroxisome |
| Impact | doi: 10.1016/j.steroids.2015.02.021 doi: 10.1042/BJ20130915 |
| Start Year | 2014 |
| Description | Rothamsted Research |
| Organisation | Rothamsted Research |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are providing expertise in mass spectrometry imaging. |
| Collaborator Contribution | Our partners are providing expertise in plant science and plant material. |
| Impact | Together we have a PhD student funded by the SWBio DTP. |
| Start Year | 2019 |
| Description | SPG5 at Athens Medical Center |
| Organisation | Athens Medical Center |
| Country | Greece |
| Sector | Hospitals |
| PI Contribution | Analysis of plasma and urine samples from SPG5 patients under a new treatment regime. |
| Collaborator Contribution | Disease diagnosis. Treatment of patients. |
| Impact | doi: 10.1016/j.biochi.2018.06.020 Collaboration between Medicine and Bioanalysis. |
| Start Year | 2015 |
| Description | SWBIO |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Department | South West Biosciences Doctoral Training Partnership |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have provided expertise and access to equipment and facilities. |
| Collaborator Contribution | Our collaborators have provided access to expertise and materials. |
| Impact | This is a multidisciplinary Doctoral Training Partnership. the current iteration of the Partnership is in its first accademic year. |
| Start Year | 2020 |
| Description | University of Houston |
| Organisation | University of Houston |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Analysis of human and transgenic mouse material. |
| Collaborator Contribution | Provision of human and transgenic mouse material. |
| Impact | doi: 10.1016/j.freeradbiomed.2018.12.020 doi: 10.1194/jlr.P071639 doi: 10.1172/JCI68506 |
| Start Year | 2013 |
| Description | University of Illinois at Chicago, |
| Organisation | University of Illinois at Chicago |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have provided expertise in cholesterol analysis in brain tissue. |
| Collaborator Contribution | Our partners have provided transgenic animal material. |
| Impact | https://doi.org/10.1101/2020.11.06.369447 |
| Start Year | 2019 |
| Description | University of Nebraska Medical Center |
| Organisation | Nebraska Medical Center |
| Country | United States |
| Sector | Hospitals |
| PI Contribution | We provided expertise for sterol analysis of brain tissue. |
| Collaborator Contribution | Our partners provided transgenic animal materials and expertise on brain development. |
| Impact | https://doi.org/10.1101/2020.11.06.369447 |
| Start Year | 2019 |
| Description | University of Queensland |
| Organisation | University of Queensland |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | Provided expertise in sterol analysis and access to equipment |
| Collaborator Contribution | Provided access to biological material |
| Impact | Publication output DOI: 10.1186/s12864-020-6505-4 Multidisciplinary collaboration, analytical science and agriculture. |
| Start Year | 2018 |
| Description | Washington University School of Medicine |
| Organisation | Washington University School of Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Oxysterol analysis. |
| Collaborator Contribution | Provision of samples. |
| Impact | DOI: 10.1016/j.freeradbiomed.2019.04.020 |
| Start Year | 2017 |
| Description | Zurich |
| Organisation | University Hospital Zürich |
| Country | Switzerland |
| Sector | Hospitals |
| PI Contribution | Analysis of tissue and blood samples from human and mouse samples. |
| Collaborator Contribution | Provision of human and mouse samples. |
| Impact | doi: 10.1194/jlr.M093229 |
| Start Year | 2016 |
| Description | 100 mins with ILS |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Seminar to lipid scientists organised by the International lipidomic society |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://lipidomicssociety.org/2021/05/17/100-minutes-with-ils-podcast/ |
| Description | BBC Wales A Healthy Future |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | BBC Radio Wales described our mass spectrometry technology and its value for disease diagnosis and discovery of novel therapeutics. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.bbc.co.uk/programmes/m0007yzp |
| Description | EpiLipidNET Work Group 1 |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Talk via Zoom to postgraduate students and professionals interested in lipidomics |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.cost.eu/actions/CA19105/#tabs+Name:Description |
| Description | Lipid Maps Spring School (1) |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | >200 researchers from across World attended the On-line Spring School in real time. All lectures are available on YouTube. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.youtube.com/watch?v=Zq-wRW_8tyI&list=PLftrKvk5gjt4CKLgC1CZaVyznBksh4O-j&index=3 |
| Description | Lipid Maps Spring School (2) |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | >200 participants attended the School in real time. The lectures are available on YouTube |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.youtube.com/watch?v=xkumM1PRwHY&list=PLftrKvk5gjt6e_0u4g3otB2Bg_J0LAXy1&index=1 |
| Description | Lipid Maps Webinar |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | I give a webinar discussing the good and bad side of cholesterol. Over 200 attended live. The presentation is available on YouTube. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.lipidmaps.org/resources/tutorials/webinars/lipidmaps/sterols_griffiths.php |
| Description | Press Release Cholesterol Imaging in Brain |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Press release stimulating increased interest in research. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.swansea.ac.uk/press-office/news-events/news/2020/05/researchers-develop-new-method-to-ma... |
| Description | Schroepfer Medal |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Award Lecture to the American Oil Chemist's Society. Lecture is available on YouTube. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.youtube.com/watch?v=J9TCRUHmNGg |