The metabolic network has a modular architecture, is robust to perturbations, and
responds to biological stimuli. The balance of the network, and the passageway of
network substructures to operate at different activity, requires intensive interactions
between the metabolic network, the transcriptome and the proteome. However, the
biochemical mechanisms monitoring the metabolic network are only barely understood.
Changes in network activity are often mediated through so called reporter metabolites:
general -network interconnecting cofactors and reaction substrates - and specific pathway
intermediates. These metabolites bridge the gap between the small molecule and
macromolecular universe of the cell.
Here we propose combining systematic yeast genetics with targeted metabolomics and
proteomics to understand mechanisms of metabolic regulation on a genome-scale level. In
principle, we will elaborate multiple reaction monitoring (MRM) assays that facilitate
quantification of enzymes and intermediates of selected metabolic pathways via liquid
chromatography tandem mass spectrometry. The analysis will be performed on metabolic
processes that influence aging; those will be analyzed and the results validated by
chemical-genetic profiling and competitive lifespan experiments.
The anticipated results will yield in a system-wide picture of interactions between the
metabolome and regulatory components of the cell. Furthermore, it will identify novel
genetic and biochemical interactions of the aging process. Understanding these
mechanisms will stimulate new research directions in Systems Biology and support the
development of therapeutic strategies against diseases of aging.
Field of science
- /natural sciences/biological sciences/genetics and heredity
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins/proteomics
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes
- /natural sciences/chemical sciences/analytical chemistry/mass spectrometry
Call for proposal
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