The role of metabolic enzymes in the nucleus (360G-Wellcome-093735_Z_10_A)
Cells exposed to oxidants re-route their main carbon flow from glycolysis to the pentose phosphate pathway (PPP), by two different mechanisms. One bases on a biochemical block and operates purely on a metabolic level, the other on transcriptional regulation. We found that the two processes compartmentalize over time: After contact with the stressor, the cell induces the metabolic transition in seconds-timescale but it takes minutes until transcripts raise. Remarkably, metabolic changes seem cau sally implicated in regulating this process: induction of the transition activates transcripts of the antioxidant-system. It is the aim of this proposal to identify and analyze regulatory mechanisms which surround the involved metabolic pathways on a genome-scale level. For this, we will develop multiple reaction monitoring (MRM) assays that allow fast quantification of metabolic intermediates, and screen an entire yeast knock-out library composed of 5,200 systematically generated yeast mutants to identify all gene deletions which cause specific changes in the concentration of their intermediates. In a second step, by using a targeted proteomics strategy, these mutants will be screened to identify alterations in the abundance of implicated enzymes. The identified genetic/metabolome interactions are studied for their general importance on metabolism, and analyzed in respect of yeast aging phenotypes.
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Grant Details
Amount Awarded | 45000 |
Applicant Surname | Ralser |
Approval Committee | Science Enhancement Committee |
Award Date | 2014-12-08T00:00:00+00:00 |
Financial Year | 2014/15 |
Grant Programme: Title | Enhancement |
Internal ID | 093735/Z/10/A |
Lead Applicant | Prof Markus Ralser |
Partnership Value | 45000 |
Planned Dates: End Date | 2016-04-30T00:00:00+00:00 |
Planned Dates: Start Date | 2015-01-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |
Sponsor(s) | Prof Stephen Oliver |