Objective
Nutritional gene regulation is of outstanding interest as a sedentary lifestyle and high calorie diet in western society increases the prevalence of metabolic disorders, e.g. diabetes and obesity. I have shown that a stress signalling pathway from the endo plasmic reticulum (ER) to the nucleus, the unfolded protein response (UPR), transduces a nitrogen signal. The read-out of the UPR, the basic leucine zipper (bZIP) transcription factor Hac1p, repressed transcription of genes activated by nitrogen-starvation.
This repression required the catalytic activity of the RPD3-SIN3 histone deacetylase (HDAC). Hac1p also activates transcription of ER chaperone genes when protein folding in the ER is inhibited. Activation by Hac1p requires the Gcn5p histone acetyltransf erase (HAT). Gcn5p activates transcription by acetylating lysine residues in core histones. Through deacetylation of an overlapping set of lysine residues Rpd3p represses transcription. This strongly suggests that interaction of Hac1p with Gcn5p and Rpd3p is tightly regulated to avoid simultaneous activation of directly opposing transcriptional regulators. To understand the mechanism that controls Hac1p function in response to environmental stimuli I propose to generate Hac1p mutants that are selectively defective in activation or repression only. Site-directed mutagenesis will be used to alter well-known features of this bZIP transcription factor. Random mutagenesis will identify additional mutants. Mutants will be scored in agar plate reporter assays and verified by Northern blotting.
Interaction of these mutants with the HDAC and HAT will be characterised using immuno-precipitation techniques. If separable, this work will identify regulatory mutants of Hac1p, which will enable database searches or genetic suppressor screens for genes that are controlling Hac1p function. This work will elucidate important aspects of how a eukaryotic cell regulates signalling specificity of an inter-organellar signalling pathway.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences computer and information sciences databases
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine endocrinology diabetes
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
- medical and health sciences health sciences nutrition obesity
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-12
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
IRG - Marie Curie actions-International re-integration grants
Coordinator
DURHAM
United Kingdom
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