Project description
Uncovering the mechanisms that promote health during intermittent fasting
Adaptation to food deprivation is a mainstay of mammal physiology. Mammals are exquisitely fitted to tolerate frequent bouts of fasting owing to fuel production by the liver (glucose, ketones). The EU-funded MemoChrom project conjectures that mammals adapt to recurring fasting by sensitising transcriptional programmes and maximising future transcriptional responses, thereby ensuring survival. The project plans to uncover transcriptional mechanisms of fasting memory that mediate the health benefits of recurrent fasting. To this end, it will profile the hepatic transcriptome and genome-wide chromatin landscape of intermittently fasting mice. Project results could help unravel fundamental homeostatic responses and significantly advance fasting research.
Objective
Adaptation to recurring environmental challenges (food availability, seasonal rhythms etc.) is a mainstay of physiology. As such, mammals are exquisitely fitted to tolerate frequent bouts of fasting owing to hepatic production of fuels (glucose, ketones). Indeed, studies show significant health benefits of intermittent fasting. Due to the reliance of the fasting response on chromatin and transcriptional regulation, I hypothesize that mammals adapt to recurring fasting by sensitizing transcriptional programs and maximizing future responses, thereby increasing survival. I plan to uncover transcriptional mechanisms of ‘fasting memory’ that mediate the health benefits of recurrent fasting. I will profile the hepatic transcriptome and genome-wide chromatin landscape of intermittently-fasted mice to discover the mediators of such memory. I will evaluate three plausible mechanisms: (1) Enhancer priming whereby the DNA regulatory elements dictating gene expression are kept in a primed state between fasting episodes. (2) Promoter priming in which RNA polymerase is paused at gene bodies during feeding and rapidly released upon re-fasting. (3) Transcriptional cascades whereby genes induced in the previous fasting bout are active in the next one, directing a second wave of gene expression. The molecular mechanisms mediating memory will be examined in a series of gain/loss of function experiments targeting various components of transcriptional regulation (transcription factors, RNA polymerase, histone and DNA modifications etc.). Both the notion of fasting memory and the cellular mechanisms driving it are supported by preliminary results. The concept raised here has the potential to unravel a fundamental homeostatic response and significantly advance fasting research. More broadly, such a discovery would reshape our view of transcriptional regulation as a cellular adaptation mechanism to recurring challenges and of physiological habituation to the environment.
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 chemical sciences organic chemistry ketones
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine physiology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences zoology mammalogy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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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.
ERC-STG - Starting Grant
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Call for proposal
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(opens in new window) ERC-2020-STG
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91904 JERUSALEM
Israel
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