Quantitative profiling

The aim of the NMC Quantitative Profiling (QP) Theme is to develop a new generation of metabolomics platforms inspired by biology and driven by technological opportunities. Two groups of projects can be distinguished:

  1. projects focussing on specific regions of the full metabolome with region selection being driven by biological needs and,
  2. projects that aim to develop innovative analytical technologies for future generation metabolomics platforms.

A total of 11 interdependent, well-aligned projects has been defined. The projects started between approx. 1 and 2.5 years ago. Progress so far has been good: platforms for phosphopeptide, oxy-lipid and isoprostane analysis have been developed, validated and transferred to the Demonstration and Competence Laboratory (DCL). These platforms are now also being applied to urgent biological questions related to chronic inflammatory disorders, regulation of life span and oxidative stress.

New hard-ware developments are investigated to extend the coverage of the NMC platforms towards more compounds and lower levels, as well as to increase throughput, accuracy and intra-laboratory comparability of quantitative data. The output in terms of papers, posters and patents is still limited but is growing: 11 posters and lectures, 16 papers and 4 patent applications. The slow start is largely due to start-up problems in combination with the revolutionary (yet not unrealistic !) nature of many of the research plans. Important achievements realised so far include the above- mentioned platforms, 150 μm micro-needles for nano-sampling from blisters and skin, a heater-less MS interface, a novel preconcentrator based on depletion zone isotachophoresis and an evaporative preconcentrator for comprehensive liquid chromatography. Prospects for success of the Theme and valorisation of the findings are very good. Many items are ready for use by others and for incorporation into improved platforms. Most of the project’s plans require little or no changes. Where necessary adequate measures have been taken to set priorities and increase output.

The relevance of the QP Theme for the NMC is as high as ever. There are great ideas about to be realised, with the demand for such improved methods remaining huge. The availability of the envisioned systems will certainly contribute to the competitive advantage of the NMC.

 
Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence.
An efficient hydrophilic interaction liquid chromatography separation of 7 phospholipid classes based on a diol column
Analytical strategies in lipidomics and applications in disease biomarker discovery.
Comprehensive LC-MS(E) Lipidomic Analysis using a Shotgun Approach and Its Application to Biomarker Detection and Identification in Osteoarthritis Patients
Enrichment of viable bacteria in a micro-volume by free-flow electrophoresis
Equating or Correction for Between-Block Effects with Application to Body Fluid LC-MS and NMR Metabolomics Data Sets
Feasibility of electrodialysis as a fast and selective sample preparation method for the profiling of low-abundant peptides in biofluids
Feasibility of electroextraction as versatile sample preconcentration for fast and sensitive analysis of urine metabolites, demonstrated on acylcarnitines
Functional implications of genetic variation in human PPARgamma
Higher mass loadability in GCxGC-MS: improved analytical performance for metabolomics analysis
Improving the analysis of designed studies by combining statistical modelling with study design information
Limits of miniaturization: assessing ITP performance in sub-micron and nanochannels
Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research
Medullary thyroid carcinoma and biomarkers: past, present and future
Mesenchymal Stem Cells Induce Resistance to Chemotherapy through the Release of platinum-Induced Fatty Acids
Nano-slit electrospray emitters fabricated by a micro- to nanofluidic via technology
Nuclear receptor-coregulator interaction profiling identifies TRIP3 as a novel peroxisome proliferator-activated receptor gamma cofactor?
On-line large-volume electroextraction coupled to liquid chromatography-mass spectrometry to improve detection of peptides
Online capillary liquid-liquid electroextraction of peptides as fast pre-concentration prior to LC-MS
P18 is a tumor suppressor gene involved in human medullary thyroid carcinoma and pheochromocytoma development
Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver
Peroxisome proliferator-activated receptor gamma regulates expression of the anti-lipolytic G-protein-coupled receptor 81 (GPR81/Gpr81)
Phaseguides: A paradigm shift in microfluidic priming and emptying
Posttranslational modifications of PPAR-gamma: fine-tuning the metabolic master regulator
Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin
Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization
RNAi-mediated transgenic Tospovirus resistance broken by intraspecies silencing suppressor protein complementation
Solution Titration by Wall Deprotonation During Capillary Filling of Silicon Oxide Nanochannels
Stable Single Walled Carbon Nanotube-Streptavidin Complex for Bio-Recognition
The DNA damage repair protein Ku70 interacts with FOXO4 to coordinate a conserved cellular stress response
The peptidyl-isomerase Pin1 regulates p27Kip1 expression through inhibition of FOXO tumorsuppressors.
Tissue Selectivity in Multiple Endocrine Neoplasia Type 1-Associated Tumorigenesis