NMC

Quantitative Profiling Project summaries

Preprocessing of hyphenated analytical data
The main goal of this project is to process raw chromatography mass spectroscopic data such that it can be used for statistics, interpretation and quality control in analytical chemistry. To this end, so called deconvolution algorithms will be developed that allow for automatic generation of peak tables and mass spectral data from large sets of chromatographic data.

Metabolomic profiling of lipid mediators in inflammation
Chronic low-grade inflammation is now considered to be central to the pathogenesis of various medical disorders like cardiovascular disease, atherosclerosis, hypertension, type 2 diabetes mellitus (T2DM) and cancer. It is well-recognized that lipid mediators like prostaglandins and leukotrienes, which are derived from arachidonic acid (AA), are local pro-inflammatory mediators. While previously viewed as a passive process, the resolution of inflammation is now considered an active process, in which specific pro-resolution circuits are activated. Interestingly, different lipid mediators which are also derived from AA, or from polyunsaturated fatty acids (PUFA), are generated during the resolution phase of inflammation, indicating that lipid mediator class switching takes place from the pro-inflammatory at the onset of inflammation to the pro-resolving at resolution. These pro-resolving mediators include lipoxins (AA-derived), resolvins (omega-3 PUFA-derived) and (neuro)protectins (omega-6 PUFA-derived). Whether deficiencies in the biosynthesis of eicosanoids might underlie some aspects of pathogenesis and complications in chronic inflammatory disorders is however completely unknown.

Development of a generic steroid platform, using adipose tissue as a model system
Steroids are critical molecules for a range of biological processes that, given their systemic mode of action, could present interesting biomarkers. Currently available techniques for measuring steroid hormones involve tedious, costly procedures such as Radio Immuno Analysis, which suffer from lack of sensitivity and are often targeted only. This thereby prevents, among others, epidemiologic analysis of low-steroid producing subjects in relation to development of disease. In addition, these approaches are used in a targeted manner rather than in a profiling mode for discovery of new biomarkers. A steroid platform will be set up that comprises selective steroid enrichment and ultrasensitive mass spectrometry-based analysis, using the endocrine adipose tissue system as a model system. The availability of in-house proteomics datasets (SILAC) and long-standing expertise on this critical model system for obesity, longevity and diabetes allows for quick validation.

Generic methods for quantitative profiling of peptides and their posttranslational modifications in body fluids and cells/tissues: development and application in disease model systems.
Despite the fact that large efforts have been made to improve methods to allow optimal detection and identification of (modified) peptides in body fluids and cells/tissues, comprehensive coverage of these molecules and of the nature and sites of peptide modification is still a huge challenge in metabolomic/peptidomics studies.The aim of this NMC core project is to develop generic methods for quantitative profiling of peptides and their posttranslational modifications. Once developed for an endocrine modelsystem (pancreatic beta cell failure in type 2 diabetes mellitus), this technology will be applied for quantitative profiling and potentially discover novel, (modified) neuropeptides and intestinal peptides (putatively) involved in neuroendocrine and metabolic regulation. Such peptides might also be used as markers for disease diagnosis, prognosis and as a guide for treatment efficacy.


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Quantitative Profiling Project summaries Preprocessing of hyphenated analytical data The main goal of this project is to process raw chromatography mass spectroscopic data such that it can be used for statistics, interpretation and quality control in analytical chemistry. To this end, so called deconvolution algorithms will be developed that allow for automatic generation of peak tables and mass spectral data from large sets of chromatographic data. Metabolomic profiling of lipid mediators in inflammation Chronic low-grade inflammation is now considered to be central to the pathogenesis of various medical disorders like cardiovascular disease, atherosclerosis, hypertension, type 2 diabetes mellitus (T2DM) and cancer. It is well-recognized that lipid mediators like prostaglandins and leukotrienes, which are derived from arachidonic acid (AA), are local pro-inflammatory mediators. While previously viewed as a passive process, the resolution of inflammation is now considered an active process, in which specific pro-resolution circuits are activated. Interestingly, different lipid mediators which are also derived from AA, or from polyunsaturated fatty acids (PUFA), are generated during the resolution phase of inflammation, indicating that lipid mediator class switching takes place from the pro-inflammatory at the onset of inflammation to the pro-resolving at resolution. These pro-resolving mediators include lipoxins (AA-derived), resolvins (omega-3 PUFA-derived) and (neuro)protectins (omega-6 PUFA-derived). Whether deficiencies in the biosynthesis of eicosanoids might underlie some aspects of pathogenesis and complications in chronic inflammatory disorders is however completely unknown. Development of a generic steroid platform, using adipose tissue as a model system Steroids are critical molecules for a range of biological processes that, given their systemic mode of action, could present interesting biomarkers. Currently available techniques for measuring steroid hormones involve tedious, costly procedures such as Radio Immuno Analysis, which suffer from lack of sensitivity and are often targeted only. This thereby prevents, among others, epidemiologic analysis of low-steroid producing subjects in relation to development of disease. In addition, these approaches are used in a targeted manner rather than in a profiling mode for discovery of new biomarkers. A steroid platform will be set up that comprises selective steroid enrichment and ultrasensitive mass spectrometry-based analysis, using the endocrine adipose tissue system as a model system. The availability of in-house proteomics datasets (SILAC) and long-standing expertise on this critical model system for obesity, longevity and diabetes allows for quick validation. Generic methods for quantitative profiling of peptides and their posttranslational modifications in body fluids and cells/tissues: development and application in disease model systems. Despite the fact that large efforts have been made to improve methods to allow optimal detection and identification of (modified) peptides in body fluids and cells/tissues, comprehensive coverage of these molecules and of the nature and sites of peptide modification is still a huge challenge in metabolomic/peptidomics studies.The aim of this NMC core project is to develop generic methods for quantitative profiling of peptides and their posttranslational modifications. Once developed for an endocrine modelsystem (pancreatic beta cell failure in type 2 diabetes mellitus), this technology will be applied for quantitative profiling and potentially discover novel, (modified) neuropeptides and intestinal peptides (putatively) involved in neuroendocrine and metabolic regulation. Such peptides might also be used as markers for disease diagnosis, prognosis and as a guide for treatment efficacy.		Life Sciences Momentum NGI The Hague, 23 November 2010 Johan Westerhuis receives EAS Award Amsterdam, March 2010 30th ISPPP - Call for Papers Bologna, Italy, 6-8 September 2010 NGI sponsors Postdoc Retreat The Hague, 21-23 April 2010 Pre-Seed Grant NGI The Hague, January 2010 Metabolomics in Nature's vision 2020 Nature Magazine 7 January 2010 Metabolomics receives first ever Impact Factor Rating UK 17 August 2009 NMC makes the difference NMC, Leiden Puzzling with metabolites NMC, NBIC, May 2009 First NMC paper published Amsterdam, Utrecht, January 2009 Robert Hall elected as secretary Metabolomics Society 11 December 2008

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