Cardiff Lipidomics Group
We use mass spectrometry to discover new lipid mediators of innate immunity and inflammation.
The ultimate goal of our research is to better understand lipid metabolism and the active role lipids play in diabetes, stroke, cancer, arthritis, Alzheimer's and other lipid-based diseases in order to facilitate development of more effective treatments.
LIPID Metabolites And Pathways Strategy (LIPID MAPS®) is a multi-institutional effort created in 2003 to identify and quantitate, using a systems biology approach and sophisticated mass spectrometers, all of the major - and many minor - lipid species in mammalian cells, as well as to quantitate the changes in these species in response to perturbation.
Since our inception, we have made great strides toward defining the "lipidome" (an inventory of the thousands of individual lipid molecular species) in the mouse macrophage. We have also worked to make lipid analysis easier and more accessible for the broader scientific community and to advance a robust research infrastructure for the international research community.
We share new lipidomics findings and methods, hold annual meetings open to all interested investigators, and are exploring joint efforts to extend the use of these powerful new methods to new application.
Our laboratory houses two AB Sciex Q-Trap instruments (4000, 6500) and a ThermoFisher Orbitrap Elite, that are available for collaborative studies at a low cost.
Our research is divided into two main themes.
Esterified Eicosanoids in innate immunity
We discovered several families of new lipids that are generated on acute activation by innate immune cells. They display diverse bioactivies including promoting coagulation and regulating leukocyte anti-bacterial responses. Our hypothesis is that they play a physiological role in wounding responses, but their dysregulation could contribute to venous thrombosis and atherosclerosis. Current studies led by the group are focused on understanding their function in health and disease
Discovery of new lipid mediators using high resolution LC/MS/MS and bioinformatic approaches
We develop new methods to enable discovery of additional lipid classes of importance for health and disease. We roughly estimate that only 50% of existing lipids in mammalian cells have been structurally characterized to date. Thus, many key discoveries remain to be made regarding this important class of endogenous biomolecules.
- Wellcome Trust Programme (£1.3m grant) to host the worlds largest curated lipid database and associated resources. The grant will allow Cardiff University’s Systems Immunity Research Institute; the Babraham Institute, Cambridge; and the University of California San Diego (UCSD) to continue the important work of identifying and analysing lipids – the molecules our bodies use to regulate normal processes such as blood clotting, fighting infection and development.
- Wellcome Trust Programme (£1.2M, 2011-2016): Aims to understand the cell biology and biophysics of the lipids and to determine their role in venous thrombosis in a clinical study.
- British Heart Foundation Programme (£820K, 2012-2017): Aims to determine the role of the new lipids in development of atherosclerosis in mouse models.
- Medical Research Council Research Grant (£820K, 2015-2019): Aims to determine the role of the lipids in normal skin physiology and wound responses in vivo.
- Wellcome Trust Enhancement Award (£120K, 2014-2016): Aims to develop total synthesis approaches for generating new lipids for biological studies.
- European Research Council Advanced Grant (€2.9M, 2014-2019). Developing a high-resolution method termed LipidArrays that will enable the diversity and number of lipids in biological samples to be characterized. We are particularly focusing on cell development, cardiovascular disease and dementia in this study. Significant method development has included developing new software in collaboration with School of Computing and Informatics.
- Friedmann Angeli, J. P. et al., 2014. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nature Cell Biology 16 , pp.1180-1191. (10.1038/ncb3064)
- Rosas, M. et al. 2014. The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal. Science 344 (6184), pp.645-648. (10.1126/science.1251414)
- Fielding, C. A. et al. 2014. Interleukin-6 signaling drives fibrosis in unresolved inflammation. Immunity 40 (1), pp.40-50. (10.1016/j.immuni.2013.10.022)
- O'Donnell, V. , Murphy, R. C. and Watson, S. P. 2014. Platelet lipidomics: modern day perspective on lipid discovery and characterization in platelets. Circulation Research 114 (7), pp.1185-1203. (10.1161/CIRCRESAHA.114.301597)
- Thomas, C. P. et al. 2014. Identification and quantification of aminophospholipid molecular species on the surface of apoptotic and activated cells. Nature Protocols 9 (1), pp.51-63. (10.1038/nprot.2013.163)
- Aldrovandi, M. et al. 2013. Human platelets generate phospholipid-esterified prostaglandins via cyclooxygenase-1 that are inhibited by low dose aspirin supplementation. Journal of Lipid Research 54 (11), pp.3085-3097. (10.1194/jlr.M041533)
Mass spectrometry and chromatography
Our facility houses three mass spectrometers which are fully geared up towards lipidomic analysis.
Techniques are available to separate, identify and quantify complex mixtures of lipids from a vast range of biological samples. Global lipidomics is also available on our accurate mass instrument.
- Technician support is available to extract lipids from your biological samples using optimised protocols.
- Beadruptor technology is available allowing us to process a wide range of tissues, including bone.
- The facility is equipped with a Tecan liquid handling robot for high sample throughput.
Triple Quad Q trap mass spectrometry
- Sciex 4000 Q trap (ES ionisation)
- Sciex 6500 Q trap (ES ionisation)
Accurate mass FTMS
- Thermo LTQ Velos Orbitrap (ES ionisation)
Analytical and technical services
We provide analytical and technical services through our experts in data acquisition and interpretation with access to a varied range of analytical equipment.
Whether it is just analysis of a single sample that is required, or more comprehensive analysis of many samples using multiple techniques, we are ideally placed to provide the answers you need.
You may be an experienced biochemist and know exactly the information you want, but if not, we could help you to identify what you need to know and how to achieve your aims.
To discuss your requirements, please contact:
Dr Victoria Tyrrell
Lipidomics Facility Manager
+44 (0)29 2068 7309