FP7Individual fellowship2009–2011

FUNGENCEL · Functional Genomics of Fatty Acid Desaturases in Caenorhabditis elegans

FP7 — People (Marie Curie Actions)

Duration
2009-04-01 → 2011-03-31
EU contribution
€171,868
Participants
1
Scheme
MC-IEF

Lines connect the coordinator with its partners.

Results in brief

Functional Genomics of Fatty Acid Desaturases in Caenorhabditis elegans

The aim of this proposal was to characterize the metabolic impact of the deletion of key genes involved in fatty acid metabolism by using the model organism Caenorhabditis elegans. In particular, the main focus of the project has been on the systemic manipulation of the expression of genes for the fatty acid desaturases to understand their key role as regulatory control points in metabolism. To achieve this aim we have made use of state of the art metabolomic approaches to provide a global, non-targeted description of systemic metabolism. The major objectives for the funding period were focused on setting a range of techniques to cover a wide range of metabolites and understanding the differences between C. elegans and mammalian metabolism, to be able to translate the results from one organism to the other in the proper manner. For this reason, the focus of the first half of the funding period was to determine the conditions for culturing, obtaining and treating C. elegans. Subsequently, the newly developed methods were used for the study of the role of desaturases in regulating the whole animal lipidome. The report is attached - we produced a short two page report and a longer one spelling out the results in more detail. Both are attached.

Data: CORDIS, © European Union

Project objective

The aim of this proposal is to characterize the metabolic impact of the expression of key transcripts involved in fatty acid metabolism by using the model organism Caenorhabditis elegans. In particular, the main focus of the project will be on the systemic manipulation of the expression of genes for the fatty acid desaturases by an RNAi based intervention to understand their key role as regulatory control points in metabolism. To achieve this aim we will make use of state of the art metabolomic approaches including Nuclear Magnetic Resonance (NMR) spectroscopy, Gas Chromatography Mass Spectroscopy (GC-MS) and Liquid chromatography Mass Spectrometry (LC-MS) to provide a global, non-targeted description of systemic metabolism. Metabolomic analysis, conducted on different genetically modified animals, will result in a rich data-base of metabolomic profiles that, with the help of multivariate data analysis techniques, will permit the identification of specific biochemical markers that determine which pathways have been perturbed. In addition, we will also analyze flux changes directly using stable isotope labelled substrates experiments. The combination of steady state concentration data and flux changes will provide a description of the reorganization of the metabolism following the targeting of a given gene by our RNAi based intervention. Overall, the results will allow a global insight into consequences of altered genetic expression across the whole system of metabolism without any loss of intrinsic complexity - a so-called top-down systems biology approach. In addition understanding the metabolic roles the desaturases play in regulating global lipid metabolism will help us to increase our understanding of human metabolic diseases associated with lipid metabolism dysfunction including obesity, type II diabetes, dyslipidaemia and the metabolic syndrome.

Original text from CORDIS.

Participants

  • THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGECoordinatorUnited Kingdom

Links

Data: CORDIS, © European Union