Objective
"Cells use sensor pathways compartmentalized in subcellular organelles to recognize stress conditions, including aberrant protein folding, and in response activate gene expression programs aimed at maintaining cell survival and restoring homeostasis. Fine-tuning of the protein-folding environment in organelles like mitochondria is important for adaptive homeostasis and may participate in development of human diseases and ageing. Work in cultured mammalian cells and more recently in Caenorhabditis elegans has highlighted the importance of mechanisms linking perturbations in the protein-folding environment in the mitochondrial matrix to the expression of nuclear genes encoding mitochondrial proteins. This mitochondrial stress pathway is named mitochondrial unfolded protein response. Much of our knowledge regarding the organelle unfolded protein response (UPR) signalling comes from studies of the endoplasmatic reticulum stress response machinery. In contrast, a potential role of mitochondria in UPR pathway is far less defined, and physiologic regulators of this pathway have not been defined.
Here I propose three complementary strategies to identify molecular mechanisms and signalling pathways of the mitochondrial unfolded protein response (UPRmt) under different stress conditions and during ageing. My laboratory has experience in using transgenic mice and C. elegans as experimental tools and both of these powerful model systems will be used in this project.
Specific aims of this proposal are:
Aim 1. To identify specific substrates of UPRmt
Aim 2. To define mechanisms regulating mammalian UPRmt
Aim 3. To elucidate the role of UPRmt signalling in ageing"
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein folding
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensors
- medical and health sciencesbasic medicinephysiologyhomeostasis
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback.
You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Call for proposal
ERC-2012-StG_20111109
See other projects for this call
Funding Scheme
ERC-SG - ERC Starting GrantHost institution
50937 Koeln
Germany