LIPMETIN-sURFing | Small open reading frames (smORF) as novel modulators of disorders of dietary excess

Summary
Dietary excess is the major origin of cardiovascular diseases and remains the leading cause of mortality. Due to difficulties with bioinformatics detection and experimental analysis, along with their sheer numbers, small open reading frames (smORF) –of fewer than 100 amino acids– have been largely disregarded. Advances in bioinformatics, RNA-sequencing (ribosome profiling), biochemical (peptidomics) and functional (genetic) screens, suggest that a large amount of smORF are transcribed and sometimes widely conserved. However, how much of these smORF-encoded peptides or small proteins (microproteins (MPs)) are translated into a functional peptide is largely unknown. Moreover, whether food bioactive components modulate the expression of MPs remains complete obscure. Thus, the main goal of this project is to search for MPs that regulate lipid metabolism in the intestine in response to dietary excess. The intellectual merits of this proposal are threefold. First, it will use cutting-edge technology to search for novel functional MPs. Second, it will address a new group of novel potential players not previously addressed in lipid metabolism, providing a novel insight into disease mechanism and innovative therapeutic strategies. Last, by testing two common food bioactive components from our healthy Mediterranean diet, we will open up a completely new field of research in the area of nutrition and health. The research approach will involve (i) a genome-wide peptidomic screen and ribosome profiling analysis of lipid-induced intestinal MPs, (ii) the use of in vivo and in vitro biochemical approximations to validate the function of the selected intestinal peptide, and (iii) the use of dietary components hydroxytyrosol and the omega-3 polyunsaturated fatty acid DHA as proof of concept that MPs can be modulated by our diet food bioactive. This project is framed in the “Food & Healthy Diet and Biotechnology” research area in the European Union's Framework Programme HORIZON 2020
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/746435
Start date: 15-01-2018
End date: 05-09-2021
Total budget - Public funding: 257 191,20 Euro - 257 191,00 Euro
Cordis data

Original description

Dietary excess is the major origin of cardiovascular diseases and remains the leading cause of mortality. Due to difficulties with bioinformatics detection and experimental analysis, along with their sheer numbers, small open reading frames (smORF) –of fewer than 100 amino acids– have been largely disregarded. Advances in bioinformatics, RNA-sequencing (ribosome profiling), biochemical (peptidomics) and functional (genetic) screens, suggest that a large amount of smORF are transcribed and sometimes widely conserved. However, how much of these smORF-encoded peptides or small proteins (microproteins (MPs)) are translated into a functional peptide is largely unknown. Moreover, whether food bioactive components modulate the expression of MPs remains complete obscure. Thus, the main goal of this project is to search for MPs that regulate lipid metabolism in the intestine in response to dietary excess. The intellectual merits of this proposal are threefold. First, it will use cutting-edge technology to search for novel functional MPs. Second, it will address a new group of novel potential players not previously addressed in lipid metabolism, providing a novel insight into disease mechanism and innovative therapeutic strategies. Last, by testing two common food bioactive components from our healthy Mediterranean diet, we will open up a completely new field of research in the area of nutrition and health. The research approach will involve (i) a genome-wide peptidomic screen and ribosome profiling analysis of lipid-induced intestinal MPs, (ii) the use of in vivo and in vitro biochemical approximations to validate the function of the selected intestinal peptide, and (iii) the use of dietary components hydroxytyrosol and the omega-3 polyunsaturated fatty acid DHA as proof of concept that MPs can be modulated by our diet food bioactive. This project is framed in the “Food & Healthy Diet and Biotechnology” research area in the European Union's Framework Programme HORIZON 2020

Status

CLOSED

Call topic

MSCA-IF-2016

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2016
MSCA-IF-2016