An Integrated platform for Quantitative Sterolomics: From Oxysterols to Bile Acids and Steroids
Lead Research Organisation:
Swansea University
Department Name: Institute of Life Science Medical School
Abstract
Cholesterol is an essential component of every animal cell. It is a structural lipid in cell membranes and the precursor of oxysterols, bile acids and steroid hormones. Cellular cholesterol homeostasis is maintained by the balance between cholesterol absorption, biosynthesis and metabolism. The first step of all cholesterol metabolism is oxidation to an oxysterol. Oxysterols are oxygenated derivatives of cholesterol which in the past have been regarded as transport forms of cholesterol returning it to the liver for conversion to bile acids. However, recent data indicates that oxysterols have biological activity, mediating a number of cholesterol-induced metabolic effects. Furthermore, down-stream acidic cholesterol metabolites, biosynthesised by many different cell types, are also biologically active. New results show that oxysterols are involved in many areas of biology e.g. acting to reduce proliferation of progenitor cells in developing brain, reducing proliferation of naive B cells and blocking class switch recombination in the immune system, offering protection against neurodegenerative disease and memory loss, and showing differential expression in malignant cells. Furthermore, bile acids, recycled by the enterohepatic system, have been shown to act as hormones by activating the G protein coupled receptor TGR5 and triggering an increase in energy expenditure and attenuation of diet-induced obesity. It is important to realise that oxysterols are a class of molecule consisting of a wide-range of distinct chemical entities. This is also true of their down-stream metabolites, and is a consequence of the initial oxidation reaction occurring at any one of many potential sites on the cholesterol molecule and the order of subsequent enzymatic biotransformations being variable. This leads to a multitude of possible metabolites. This complexity is similarly reflected in bile acids which can be structurally-transformed by bacteria in the enterohepatic system. Cholesterol metabolites are challenging molecules to analyse in biological systems. This is a consequence of their low abundance against a high background of cholesterol (e.g. ng oxysterol / microg cholesterol in brain, ng bile acid / mg cholesterol in plasma, pg neurosteroid / microg cholesterol in CSF), the propensity of cholesterol to be oxidised in air to oxysterols (and also to C19 & C21 steroids) there-by generating analytical artefacts, and their lack of a strong chromophore but thermal lability. The consequence of this is that comprehensive cholesterol metabolite profiles are poorly described in body fluids, tissues and cell types. In this proposal we intend to meet this challenge by developing an integrated mass spectrometry-based platform for the ultra-high sensitivity quantitative and structural determination of cholesterol metabolites in biological systems. We will introduce new technology based on chemical-tagging to enhance the analysis of cholesterol metabolites, their structural determination, and quantification. By exploiting stable-isotope labelling in the charge-tags we will be able to determine absolute quantities of specific metabolites and also perform relative quantification of untargeted metabolites between different samples e.g. between different locations in brain or between different cell types. Through international collaboration we will investigate the biological activity of the identified metabolites in defined biological assays. This project is likely to have impact with respect to healthy aging, and as deranged cholesterol synthesis and metabolism is implicated in numerous disease states (neurodegenerative disease; atherosclerosis; diabetes) and malformation syndromes will be of benefit to UK pharma and those involved in biomarker discovery and clinical screening.
Technical Summary
The primary objective of the current proposal is to develop an integrated mass spectrometry (MS)-based platform for the quantitative and structural determination of cholesterol metabolites in biological systems. This will be supplemented by assays of their bioactivity. Over the last 20 years the focus of the PI's research has been the identification and quantification of oxysterols, bile acids and steroids in body fluids, tissues and cell types. While many molecules in these classes can be analysed at high sensitivity in targeted analysis by MS, usually utilising multiple reaction monitoring (MRM) or selected-ion recording (SIR), such analysis require pre-defined targets and are not suitable for profile analysis or the identification of unknown or unexpected components. Furthermore accurate quantification requires an isotope-labelled internal standard. In recent years we have developed an alternative strategy based on charge-tagging and LC-MSn for the ultra-high sensitivity identification and quantification of cholesterol metabolites. By utilising simple chemistry we tag a charged group to a ketone group on cholesterol metabolites, this improves the LC-MS response by two - three orders of magnitude. Further, the nature of the derivative enhances the information content of MSn spectra, allowing structure determination and identification of unknowns. In this proposal we seek to move this methodology to the next level by incorporating stable-isotope labelling in the charge-tag thereby allowing absolute quantification of individual samples and relative quantification between samples. Further, we will extend the number of metabolites amenable to charge-tagging by incorporating enzymatic conversion of alcohol functions to ketone groups (thus available for derivatisation).
Planned Impact
The primary objective of the current proposal is to develop an integrated mass spectrometry (MS)-based platform for the quantitative and structural determination of cholesterol metabolites in biological systems. As part of this proposal we will create a series of isotope-coded charge tags for use in ultra-high sensitivity quantitative studies. The isotope-coded charge tags will offer improved analyte sensitivity and allow absolute quantification of defined analytes and relative quantification (between samples) of undefined targets. We will further develop the tagging chemistry to allow charge-tagging to alcohol (3beta and 3alfa hydroxyl groups on the steroid skeleton) functionalities in addition to oxo (ketone/aldehyde) groups. Although in this study we will concentrate our attention on the analysis of cholesterol metabolites, the developed isotope-coded charge tags will be equally useful in other areas of lipidomics and metabolomics. The likely beneficiaries of our analytical platform are analysts working in the areas of metabolomics, lipidomics, biomarker discovery, clinical screening and doping control. The methods generated by the present study will be valuable to those working in the sterol bile acid and steroid fields, including contract research, pharmaceutical companies, and doping and clinical laboratories. The analytical methods are likely to be important in neuroscience, particularly for the prediction and monitoring of neurodegenerative disease, and in stem cell biology, cancer and immunology where specific cholesterol metabolites have been shown to be important in influencing cell proliferation. We will publish our data in peer review journals, make presentations at international meetings and also establish a website where data and methods will be freely available. We will also present our data to the general public at public seminars, open days and visits to schools. With respect to commercialisation we are collaborating with Proteome Sciences plc in the area of isotope-coded tags for tandem mass spectrometry in metabolomics, and we would negotiate with them to commercialisation our isotope-coded charge tags. The research has considerable potential impact on the nation's health and wellbeing. We plan (in future studies) to utilise our analytical platform to validate potential cholesterol derived metabolites as markers for the early diagnosis of Alzheimer's disease. Early diagnosis will be important as new treatments; both pharmacological and psychological are being developed. The research may also have an impact in the development of regenerative therapies for Parkinson's disease as cholesterol metabolites have been found to be important in the development of dopaminergic neurons from stem cells. The PDRA employed in this project will gain an expert education in biological mass spectrometry; which can in the future be exported to all areas of analytical science. Further, the project is at the interface of chemistry, biology and medicine and is thus multidisciplinary. Cholesterol metabolites identified to have biological activity will be patented in association with Swansea University. We will seek to exploit commercially our isotope-coded charge tags in collaboration with Proteome Sciences plc.
Organisations
- Swansea University (Lead Research Organisation)
- Engineering and Physical Sciences Research Council (Co-funder)
- University Hospital Regensburg (Collaboration)
- Eberhard Karls University of Tübingen (Collaboration)
- University of Basel (Collaboration)
- Karolinska Institute (Collaboration)
- University of Regensburg (Collaboration)
- University of Oslo (Collaboration)
- University Hospital of Basel (Collaboration)
- Case Western Reserve University (Collaboration)
- Athens Medical Center (Collaboration)
- University of Southern Denmark (Collaboration)
- Umea University (Collaboration)
- University of Clermont Auvergne (Collaboration)
- UNIVERSITY OF EDINBURGH (Collaboration)
- Oregon Health and Science University (Collaboration)
- Cardiff University (Collaboration)
- Washington University School of Medicine (Collaboration)
- University of Queensland (Collaboration)
- University College London (Collaboration)
- University of Manchester (Collaboration)
- University of Franche-Comté (Collaboration)
- Babraham Institute (Collaboration)
- Washington University in St. Louis (Collaboration)
- Novartis (Collaboration)
- University of Houston (Collaboration)
- Université Catholique de Louvain (Collaboration)
- University Hospital Zürich (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- University of Toulouse (Collaboration)
- Duke University (Collaboration)
- UNIVERSITY OF GLASGOW (Collaboration)
- Medical University of Graz (Collaboration)
- University of Pardubice (Collaboration)
- Minerva Foundation Institute for Medical Research (Collaboration)
- University of Leuven (Collaboration)
- University of Texas Southwestern Medical Center (Collaboration)
- Children's Hospital Oakland Research Institute (CHORI) (Collaboration)
Publications
Hudson N
(2020)
Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle
in BMC Genomics
Höflinger P
(2021)
Metabolic profiling in serum, cerebrospinal fluid, and brain of patients with cerebrotendinous xanthomatosis.
in Journal of lipid research
Iuliano L
(2015)
Cholesterol metabolites exported from human brain.
in Steroids
Karu K
(2011)
Nano-liquid chromatography-tandem mass spectrometry analysis of oxysterols in brain: monitoring of cholesterol autoxidation.
in Chemistry and physics of lipids
Kurowska-Stolarska M
(2017)
The role of microRNA-155/liver X receptor pathway in experimental and idiopathic pulmonary fibrosis.
in The Journal of allergy and clinical immunology
Liebisch G
(2013)
Shorthand notation for lipid structures derived from mass spectrometry.
in Journal of lipid research
Lütjohann D
(2019)
First international descriptive and interventional survey for cholesterol and non-cholesterol sterol determination by gas- and liquid-chromatography-Urgent need for harmonisation of analytical methods.
in The Journal of steroid biochemistry and molecular biology
Mazein A
(2013)
A comprehensive machine-readable view of the mammalian cholesterol biosynthesis pathway.
in Biochemical pharmacology
Meljon A
(2012)
Analysis of bioactive oxysterols in newborn mouse brain by LC/MS.
in Journal of lipid research
Meljon A
(2013)
Analysis by liquid chromatography-mass spectrometry of sterols and oxysterols in brain of the newborn Dhcr7(?3-5/T93M) mouse: a model of Smith-Lemli-Opitz syndrome.
in Biochemical pharmacology
Meljon A
(2014)
Oxysterols in the brain of the cholesterol 24-hydroxylase knockout mouse.
in Biochemical and biophysical research communications
Meljon A
(2019)
Mining for Oxysterols in Cyp7b1-/- Mouse Brain and Plasma: Relevance to Spastic Paraplegia Type 5.
in Biomolecules
Ormsby TJR
(2021)
Oxysterols protect bovine endometrial cells against pore-forming toxins from pathogenic bacteria.
in FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Rees DO
(2017)
Comparison of the composition of bile acids in bile of patients with adenocarcinoma of the pancreas and benign disease.
in The Journal of steroid biochemistry and molecular biology
Saeed AA
(2014)
Effects of a disrupted blood-brain barrier on cholesterol homeostasis in the brain.
in The Journal of biological chemistry
Theofilopoulos S
(2014)
Cholestenoic acids regulate motor neuron survival via liver X receptors.
in The Journal of clinical investigation
Theofilopoulos S
(2013)
Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis.
in Nature chemical biology
Theofilopoulos S
(2019)
24(S),25-Epoxycholesterol and cholesterol 24S-hydroxylase (CYP46A1) overexpression promote midbrain dopaminergic neurogenesis in vivo.
in The Journal of biological chemistry
Wang Y
(2014)
24S,25-Epoxycholesterol in mouse and rat brain.
in Biochemical and biophysical research communications
Wang Y
(2021)
Neuro-oxysterols and neuro-sterols as ligands to nuclear receptors, GPCRs, ligand-gated ion channels and other protein receptors.
in British journal of pharmacology
Wang Y
(2018)
Unravelling new pathways of sterol metabolism: lessons learned from in-born errors and cancer.
in Current opinion in clinical nutrition and metabolic care
Yutuc E
(2021)
Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry.
in Analytica chimica acta
Yutuc E
(2020)
Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism.
in Proceedings of the National Academy of Sciences of the United States of America
Description | Below we describe the objectives of the project and the progress made: A. Create a series of isotope-coded charge tags for use in ultra-high sensitivity quantitative (absolute and relative) lipidomics. We have achieved this objective and applied for a patent:- "Kit and method for quantitative detection of steroids" Application No. GB1215924.0. We have described the method at international meetings (2nd ENOR Symposium, Oxysterols and Related Sterols in Chemistry, Biology and Medicine, Dijon 20-21 September 2012; and 20th International Mass Spectrometry Conference, Geneva, August 24-29, 2014). The method is published in Clinical Chemistry 2014. B. Exemplify the developed LC-MSn platform in the discovery and quantification of oxysterols/bile acids/steroids in biological fluids, tissues and specific cells types. Through collaboration with clinicians we have exploited our methodology in the comprehensive profiling of plasma sterols, with particular reference to inborn errors of metabolism. We have used the method to provide biochemical support to our discovery that chenodeoxycholic acid can be successfully used in the treatment of oxysterol 7alpha-hydroxylase deficiency. In collaboration with a pharmaceutical company we performed similar studies on cerebrospinal fluid (CSF) from patients suffering neural inflammation. We have further exploited our methodology for oxysterol analysis in tissues and in virus infected cells. This work has resulted in publications in Journal of Lipid Research, Journal of Inherited Metabolic Disease and in the journal Immunity. We have C. Generate a LC-MSn library of charge-tagged oxysterols/bile acids/steroids for use by the lipidomic and metabolomic communities. The library can be found at http://sterolanalysis.org.uk/?page=Home D. Through collaboration with colleagues in Karolinska Institutet we investigate whether the identified compounds activate nuclear receptors in relevant cell systems. In collaboration with colleagues in Karolinska Institutet we have identified cholic acid as a new LXR ligand in brain and 24S,25-epoxycholesterol as the most abundant LXR ligand in developing mouse midbrain. Notably, each ligand selectively regulated the development of distinct midbrain neuronal populations. Whereas cholic acid increased survival and neurogenesis of Brn3a-positive red nucleus neurons, 24S,25-epoxycholesterol promoted dopaminergic neurogenesis. These results identify an entirely new class of highly selective and cell type-specific regulators of neurogenesis and neuronal survival. Moreover, 24S,25-epoxycholesterol promoted dopaminergic differentiation of embryonic stem cells, suggesting that LXR ligands may thus contribute to the development of cell replacement and regenerative therapies for Parkinson's disease. This study was published in the journal Nature Chemical Biology. In a related study on human we have identified 3ß,7a-dihydroxycholest-5-en-26-oic acid as an LXR ligand which promotes the survival of oculomotor neurons. We have made a patent application "Compound and Method for the Treatment of Neurodegenerative Conditions" Application No. GB1303589.4 to protect these discoveries. The study is published in the Journal of Clinical Investigation. |
Exploitation Route | 1. We have collaborated with a pharmaceutical company on a project where our isotope-coded charge tags were directly utilized. 2. We have licenced our isotope-coded charge tags to Avanti Polar Lipids Inc and to Cayman Chemical Company. 3. The discovery of LXR ligands as cell type-specific regulators of neurogenesis and neuronal survival may lead to potential treatments for conditions such as Parkinson's disease and motor neuron disease. 4. To-date, the key activity towards exploiting the impact of our discoveries is through the patent applications "Kit and method for quantitative detection of steroids" and "Compound and Method for the Treatment of Neurodegenerative Conditions". 5. Our discovery of chenodeoxycholic acid as a treatment for oxysterol 7alpha-hydroxylase deficiency has lead to the initiation of clinical trials. 6. We have discovered a novel modulators for the Hedgehog signalling pathway. |
Sectors | Agriculture Food and Drink Chemicals Healthcare Pharmaceuticals and Medical Biotechnology |
URL | https://www.swansea.ac.uk/staff/medicine/research/griffithswj/ |
Description | The findings from this study have resulted in five patent applications 1. "Kit and method for quantitative detection of steroids" Application No. GB1215924.0; (granted US9851368B2) 2. "Compound and Method for the Treatment of Neurodegenerative Conditions" Application No. GB1303589.4; 3. "Deuterated compounds" Application No. GB 1316050.2 (granted EP3044192B1, JP2016530289A); 4."Diagnostic methods and kits" Application No. GB1516441.1 (granted EP3345004B1). 5. "Diagnostic Methods and Kits" Application No.GB2016/052710 (granted US11536730B2, EP3513195B1). Our discovery of chenodeoxycholic acid as a treatment for oxysterol 7alpha-hydroxylase deficiency has prompted clinical trials. The methodology developed in this award is being used to support the clinical trials. The "Kit" has been licensed to Avanti Polar Lipids Inc and Cayman Chemical Company. |
First Year Of Impact | 2018 |
Sector | Agriculture, Food and Drink,Chemicals,Healthcare,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 | Lipid Nomenclature |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Impact | Up-date on classification, nomenclature, and shorthand notation for lipid structures. |
URL | https://www.lipidmaps.org/about/index.php |
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 | 12/2020 |
End | 12/2024 |
Description | A4B |
Amount | £66,240 (GBP) |
Organisation | Welsh Assembly |
Sector | Public |
Country | United Kingdom |
Start | 03/2014 |
End | 12/2014 |
Description | A4B |
Amount | £378,057 (GBP) |
Funding ID | HE09161003 |
Organisation | Government of Wales |
Sector | Public |
Country | United Kingdom |
Start | 09/2013 |
End | 12/2014 |
Description | BBSRC Responsive mode |
Amount | £460,386 (GBP) |
Funding ID | BB/N015932/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2019 |
Description | Follow on Fund |
Amount | £10,954 (GBP) |
Funding ID | BB/FOF/PF/15/13 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2013 |
End | 03/2014 |
Description | KESS II |
Amount | £53,476 (GBP) |
Funding ID | EGR817 |
Organisation | Government of Wales |
Sector | Public |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2019 |
Description | Life Sciences Research Network Wales |
Amount | £50,000 (GBP) |
Organisation | Government of Wales |
Sector | Public |
Country | United Kingdom |
Start | 03/2015 |
End | 02/2016 |
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 | 03/2019 |
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 | Michael J. Fox Foundation's Targeted RFA (Lipidomics) |
Amount | $376,119 (USD) |
Funding ID | 16231 |
Organisation | Michael J Fox Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 05/2019 |
End | 05/2021 |
Description | Responsive |
Amount | £652,000 (GBP) |
Funding ID | BB/K019112/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2013 |
End | 06/2016 |
Description | Responsive Mode |
Amount | £382,198 (GBP) |
Funding ID | BB/L001942/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2014 |
End | 01/2017 |
Description | SHIPP INITIATIVE |
Amount | £36,000 (GBP) |
Funding ID | SHIPP-0001 |
Organisation | Government of Wales |
Sector | Public |
Country | United Kingdom |
Start | 06/2016 |
End | 02/2017 |
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 | 09/2022 |
End | 03/2023 |
Description | Sterol Characterization and Biomarker Discovery in PD CSF and Plasma |
Amount | £258,940 (GBP) |
Funding ID | MJFF-021150 |
Organisation | Michael J Fox Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2022 |
End | 08/2023 |
Description | Sterol and Oxysterol Markers of Huntington's Disease: The 24SHydroxycholesterol Pathway |
Amount | £277,217 (GBP) |
Organisation | CHDI Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 09/2020 |
End | 09/2022 |
Title | EADSA |
Description | We have developed a charge-tagging approach to greatly enhance mass spectrometry sensitivity for biomolecule analysis. |
Type Of Material | Technology assay or reagent |
Year Produced | 2011 |
Provided To Others? | Yes |
Impact | Allowed the identification of novel cholesterol metabolites in biological systems. |
Title | Additional file 1 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 1. A multitab Excel spreadsheet containing the lists of genes satisfying sets of criteria indicative of their likely cell type (e.g. IMF adipocyte) of origin. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_1_of_Gene_expression_identifies_metabol... |
Title | Additional file 1 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 1. A multitab Excel spreadsheet containing the lists of genes satisfying sets of criteria indicative of their likely cell type (e.g. IMF adipocyte) of origin. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_1_of_Gene_expression_identifies_metabol... |
Title | Additional file 2 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 2. A CSV file containing the log 2 normalised mean expression for all 96 individual tissue samples (3 genotypes, 2 diets for intact LD muscle only, 6 tissues and 4 individual replicates per treatment cell) used in this analysis. (CSV 25668 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_2_of_Gene_expression_identifies_metabol... |
Title | Additional file 2 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 2. A CSV file containing the log 2 normalised mean expression for all 96 individual tissue samples (3 genotypes, 2 diets for intact LD muscle only, 6 tissues and 4 individual replicates per treatment cell) used in this analysis. (CSV 25668 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_2_of_Gene_expression_identifies_metabol... |
Title | Additional file 4 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 4. An HTM file containing the SAS correlation output for the metabolites and carcass phenotypes. (HTM 232 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_4_of_Gene_expression_identifies_metabol... |
Title | Additional file 4 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 4. An HTM file containing the SAS correlation output for the metabolites and carcass phenotypes. (HTM 232 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_4_of_Gene_expression_identifies_metabol... |
Title | Additional file 5 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 5. The genome-wide P values associated with differential expression between the IMF versus SC depots. Significance was established using t tests assuming equal variance. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_5_of_Gene_expression_identifies_metabol... |
Title | Additional file 5 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 5. The genome-wide P values associated with differential expression between the IMF versus SC depots. Significance was established using t tests assuming equal variance. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_5_of_Gene_expression_identifies_metabol... |
Title | Additional file 6 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 6. The genome-wide P values associated with the Phenotypic Impact Factor (PIF) values computed for the IMF versus SC depots. Significance was established from z scores processed through an inverse normal distribution to produce 1 tailed P values. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_6_of_Gene_expression_identifies_metabol... |
Title | Additional file 6 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 6. The genome-wide P values associated with the Phenotypic Impact Factor (PIF) values computed for the IMF versus SC depots. Significance was established from z scores processed through an inverse normal distribution to produce 1 tailed P values. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_6_of_Gene_expression_identifies_metabol... |
Title | Additional file 7 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 7. An excel spreadsheet containing the Minus and Average (MA) data to recreate the IMF versus SC MA plot, with values for 14,476 probes (one probe per gene). The extreme 1 and 5% by PIF are also listed here. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_7_of_Gene_expression_identifies_metabol... |
Title | Additional file 7 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 7. An excel spreadsheet containing the Minus and Average (MA) data to recreate the IMF versus SC MA plot, with values for 14,476 probes (one probe per gene). The extreme 1 and 5% by PIF are also listed here. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_7_of_Gene_expression_identifies_metabol... |
Title | Additional file 8 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 8. The carcass phenotypes for those animals whose plasma was quantitated for oxysterols. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_8_of_Gene_expression_identifies_metabol... |
Title | Additional file 8 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 8. The carcass phenotypes for those animals whose plasma was quantitated for oxysterols. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_8_of_Gene_expression_identifies_metabol... |
Title | Additional file 9 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 9. The oxysterol quantitation data for the 8 selected animals. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_9_of_Gene_expression_identifies_metabol... |
Title | Additional file 9 of Gene expression identifies metabolic and functional differences between intramuscular and subcutaneous adipocytes in cattle |
Description | Additional file 9. The oxysterol quantitation data for the 8 selected animals. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_9_of_Gene_expression_identifies_metabol... |
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: 10.1126/sciadv.adj1354 DOI: 10.1093/braincomms/fcad228 doi: 10.1016/j.jsbmb.2019.105475 doi: 10.1016/j.jsbmb.2020.105794 |
Start Year | 2007 |
Description | CHORI: Inborn errors of metabolism |
Organisation | Children's Hospital Oakland Research Institute (CHORI) |
Country | United States |
Sector | Hospitals |
PI Contribution | Analysis of patient and mouse model samples. |
Collaborator Contribution | Provision of patient and mouse model samples. Expertise in inborn errors of metabolism. |
Impact | doi: 10.1016/j.jsbmb.2020.105794 doi: 10.1016/j.jsbmb.2016.03.018 doi: 10.1016/j.bcp.2013.03.003 doi: 10.1194/jlr.D028233 doi: 10.1373/clinchem.2007.100644 |
Start Year | 2007 |
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 DOI: 10.1093/brain/awae028 |
Start Year | 2018 |
Description | Duke University |
Organisation | Duke University |
Country | United States |
Sector | Academic/University |
PI Contribution | Analysis of brain and plasma samples |
Collaborator Contribution | Provision of samples |
Impact | doi: 10.1016/j.xcrm.2020.100138 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
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 DOI: 10.1016/j.jsbmb.2024.106495 |
Start Year | 2010 |
Description | Edin |
Organisation | Cardiff University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have provided intellectual input and data. |
Collaborator Contribution | Edinburgh has provided intellectual input and data. |
Impact | doi: 10.1016/j.immuni.2012.11.004 doi: 10.1016/j.bcp.2013.03.021 doi: 10.1371/journal.pbio.1002364 |
Start Year | 2012 |
Description | Edin |
Organisation | University of Edinburgh |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have provided intellectual input and data. |
Collaborator Contribution | Edinburgh has provided intellectual input and data. |
Impact | doi: 10.1016/j.immuni.2012.11.004 doi: 10.1016/j.bcp.2013.03.021 doi: 10.1371/journal.pbio.1002364 |
Start Year | 2012 |
Description | Hereditary Spastic Paraplegia |
Organisation | Eberhard Karls University of Tübingen |
Department | Centre of Neurology and Hertie-Institute for Clinical Brain Research |
Country | Germany |
Sector | Academic/University |
PI Contribution | Expertise in oxysterol and sterol analysis. |
Collaborator Contribution | Hepatocyte and cortical neuron differentiation from iPS cells. Clinical samples from patients with in born errors of metabolism |
Impact | doi: 10.1172/JCI68506 doi.org/10.1016/j.aca.2021.338259 Analytical science and medicine |
Start Year | 2014 |
Description | ICH: Inborn errors of metabolism |
Organisation | University College London |
Department | Institute of Child Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Investigation of inborn errors of cholesterol biosynthesis and metabolism. |
Collaborator Contribution | Clinical information concerning inborn errors of metabolism |
Impact | Four publications |
Start Year | 2009 |
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 | Manchester: Collaboration on inborn errors of metabolism |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Analysis of plasma and urine samples in the study of inborn errors of cholesterol biosynthesis and metabolism. |
Collaborator Contribution | Provision of samples for the study of inborn errors of cholesterol biosynthesis and metabolism. |
Impact | doi: 10.1016/j.freeradbiomed.2019.04.020 doi: 10.1194/jlr.D083246 doi: 10.1016/j.jsbmb.2020.105794 doi: 10.1016/j.jsbmb.2016.03.018 doi: 10.1373/clinchem.2014.231332 doi: 10.1172/JCI68506 doi: 10.1016/j.freeradbiomed.2012.07.027 Multidisciplinary, medicine and analytical science. |
Start Year | 2012 |
Description | Motor Neuron Disease |
Organisation | University of Oxford |
Department | Nuffield Department of Clinical Neurosciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in sterol and oxysterol analysis |
Collaborator Contribution | Expertise in motor neuron disease clinical pathology |
Impact | doi: 10.1194/jlr.P071639 WO2018007803A1 |
Start Year | 2014 |
Description | Multiple Sclerosis |
Organisation | University Hospital Basel |
Country | Switzerland |
Sector | Hospitals |
PI Contribution | Expertise in sterol and oxysterol analysis. |
Collaborator Contribution | Expertise in multiple sclerosis pathology |
Impact | doi: 10.1172/JCI68506 doi: 10.1007/s12035-016-0281-9 |
Start Year | 2014 |
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 | Oxford Centre for Diabetes, Endocrinology & Metabolism |
Organisation | University of Oxford |
Department | Oxford Hub |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in the analysis of oxysterols |
Collaborator Contribution | Provision of valuable biological material |
Impact | Joint grant application made. |
Start Year | 2023 |
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 | Pulmonary Fibrosis |
Organisation | University of Glasgow |
Department | College of Arts |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in sterol/oxysterol analysis |
Collaborator Contribution | Expertise in the pathology of pulmonary fibrosis |
Impact | doi: 10.1016/j.jaci.2016.09.021 |
Start Year | 2014 |
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; DOI: 10.1016/j.isci.2023.108670 Collaboration between Medicine and Bioanalysis. |
Start Year | 2015 |
Description | UMEÅ UNIVERSITY |
Organisation | Umea University |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Lipidomic analysis of plasma and CSF samples |
Collaborator Contribution | Provision of patient material |
Impact | https://doi.org/10.1016/j.aca.2021.338259 |
Start Year | 2018 |
Description | Université de Bourgogne-Franche Comté |
Organisation | University of Franche-Comté |
Country | France |
Sector | Academic/University |
PI Contribution | expertise, intellectual input, data |
Collaborator Contribution | access to biological materials |
Impact | doi: 10.1016/j.biochi.2018.02.008. |
Start Year | 2017 |
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 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 Grant application to NIH. |
Start Year | 2017 |
Description | Washington University in St. Louis - TB |
Organisation | Washington University in St Louis |
Country | United States |
Sector | Academic/University |
PI Contribution | We are analyzing materials for oxysterols. |
Collaborator Contribution | Washington University are providing material for oxysterol analysis |
Impact | Successful grant application NIH. Award number 1R01AI178685-01A1. Presentation "Cholesterol 25-hydroxylase promotes survival and modulates immune cell recruitment to the lung during Mycobacterium tuberculosis infection" at the 2024 American Thoracic Society annual meeting. |
Start Year | 2021 |
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 |
Title | COMPOUND AND METHOD FOR THE TREATMENT AND DIAGNOSIS OF NEURODEGENERATIVE CONDITIONS |
Description | A reagent selected from cholestenoic acid or an inhibitor of an enzyme in the cholestenoic acid biosynthetic or metabolic pathway for use in the treatment of neurodegenerative conditions. In particular, the reagent is a cholestenoic acid of a particular form, such as 3&bgr;,7a-dihydroxycholest-5 -en-26-oic (3&bgr;,7a-di HCA), not previously associated with neural tissue or CSF. Pharmaceutical compositions, methods of treatment or prevention of neurodegenerative conditions as well as diagnostic methods and novel biomarkers form further aspects of the invention. |
IP Reference | WO2014132052 |
Protection | Patent application published |
Year Protection Granted | 2014 |
Licensed | No |
Impact | Impact has yet to arrive. |
Title | DEUTERATED COMPOUNDS |
Description | Compounds of general formula (I) wherein (I) R1 - R4 are each independently selected from H and deuterium; and at least one of R1 - R4 is deuterium. The compounds have been found to be particularly useful for treating neurodegenerative conditions and in particular but not exclusively conditions such as motor neurone disease. |
IP Reference | WO2015036726 |
Protection | Patent application published |
Year Protection Granted | 2015 |
Licensed | No |
Impact | Impact has yet to arise. |
Title | DEUTERATED COMPOUNDS |
Description | Compounds of general formula (I) wherein (I) R1 - R4 are each independently selected from H and deuterium; and at least one of R1 - R4 is deuterium. The compounds have been found to be particularly useful for treating neurodegenerative conditions and in particular but not exclusively conditions such as motor neurone disease. |
IP Reference | WO2015036726 |
Protection | Patent granted |
Year Protection Granted | 2015 |
Licensed | No |
Impact | Spinout company formed. |
Title | DIAGNOSTIC METHODS AND KITS |
Description | According to the present invention there is provided a method for diagnosing Smith-Lemli-Opitz syndrome (SLOS) comprising detecting levels of the compound of formula (I) or a derivative thereof in a urine sample from a subject suspected of or suffering from SLOS, or from a urine sample from an expectant mother comparing these with the levels found in healthy subject which are higher than those found in a sample from a subject not suffering from SLOS. |
IP Reference | EP3345004 |
Protection | Patent / Patent application |
Year Protection Granted | 2018 |
Licensed | Yes |
Impact | Swansea University has licensed the patent to CholesteniX Ltd. |
Title | Diagnostic methods and kits |
Description | Diagnostic method for identification of an inborn error of cholesterol biosynthesis. |
IP Reference | GB1611636.0 |
Protection | Patent application published |
Year Protection Granted | 2016 |
Licensed | No |
Impact | Patent application has been made. |
Title | KIT AND METHOD FOR QUANTITATIVE DETECTION OF STEROIDS |
Description | The invention relates to a kit and methods for quantitative detection of steroids in a sample. The kit comprises quantitative charge tags and an oxidising agent. |
IP Reference | WO2014037725 |
Protection | Patent application published |
Year Protection Granted | 2014 |
Licensed | Yes |
Impact | The kit will be commercialised by Avanti Polar Lipids |
Title | KIT AND METHOD FOR QUANTITATIVE DETECTION OF STEROIDS |
Description | The present invention relates to a kit for the quantitative detection of steroids and to methods for using the kit. In particular, the method relates to a kit which enables steroids to be quantitatively detected using mass spectrometry. |
IP Reference | GB1215924.0 |
Protection | Patent application published |
Year Protection Granted | |
Licensed | No |
Impact | The discovery has been exploited for academic work. |
Title | METHODS FOR DIAGNOSING MOTOR NEURON DISEASES |
Description | The invention relates to methods for determining whether a subject is afflicted with a motor neuron disease, the method comprising conducting an analysis of cerebrospinal fluid and/or plasma, measuring the level of one or more sterol/oxysterol analytes, and comparing these to reference values. Further, the invention relates to methods of identifying agents suitable for the treatment of MND, and monitoring the progress of the disease. |
IP Reference | US2019310267 |
Protection | Patent / Patent application |
Year Protection Granted | 2019 |
Licensed | Yes |
Impact | Other patents granted: EP 3 513 195 B1 |
Title | CYP7B1 |
Description | The drug is in clinical trials. |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2016 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | The drug is in clinical trials for the treatment of a rare disease. |
URL | https://clinicaltrials.gov/show/NCT02314208 |
Title | Diagnostic test |
Description | Diagnostic test for inborn errors of cholesterol biosynthesis and metabolism. Seeking support to develop the test further. |
Type | Diagnostic Tool - Non-Imaging |
Current Stage Of Development | Initial development |
Year Development Stage Completed | 2018 |
Development Status | Actively seeking support |
Impact | Used to monitor response to treatment. |
Company Name | Cholestenix Limited |
Description | CholesteniX is a company focused on developing new treatments and biomarkers for neurodegenerative diseases, specifically motor neuron disease. |
Year Established | 2013 |
Impact | none as yet |
Website | http://www.oxandia.com |
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 | ASBMB Cholesterol and ALS |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Article in ASBMB monthly magazine |
Year(s) Of Engagement Activity | 2016 |
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 | Cholesterol and ALS |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press release to communicate latest scientific discovery. Many email responses from motor neuron disease sufferers or carers. |
Year(s) Of Engagement Activity | 2016 |
Description | Cholesterol metabolites regulate motor neuron function |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | A research highlight was published in Nature Reviews Endocrinology. NA |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.nature.com/nrendo/journal/vaop/ncurrent/full/nrendo.2014.184.html |
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 | ILS Clinical Lipidomics |
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 | On-line talk on Clinical Lipidomics. |
Year(s) Of Engagement Activity | 2022 |
URL | https://lipidomicssociety.org/interest_groups/clinical-lipidomics/ |
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 | New steroid discovery could improve Parkinson's treatment; |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Scientists at Swansea University and Karolinska Institutet in Stockholm have identified two steroid-type molecules that play an important role in the survival and production of nerve cells in the brain. The discovery, published in the journal Nature Chemical Biology, could help in the development of new treatments for neurological diseases such as Parkinson's disease. no actual impacts realised to date |
Year(s) Of Engagement Activity | 2013 |
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 |
Description | Steroids: Scientists examine controversial substance's potential to treat Parkinson's, http://www.walesonline.co.uk/news/wales-news/steroids-scientists-examine-controversial-substances-2496776 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Steroids could be used to treat a debilitating disease that affects thousands in Wales today. Researchers at a University in Wales have highlighted the controversial substance's positive side after discovering two steroid type molecules that could treat Parkinson's disease no actual impacts realised to date |
Year(s) Of Engagement Activity | 2013 |