H2020Индивидуална стипендия2018–2021

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-01-15 → 2021-09-05
Финансиране от ЕС: 257 191 €
Участници: 2
Схема: MSCA-IF-GF

Линиите свързват координатора с партньорите.

Накратко на български

Микропротеини в червните клетки може да регулират начина, по който тялото усвоява мазнините от храната. Разбирането на техните функции помага при изследването на сърдечно-съдови заболявания и нарушения в метаболизма, причинени от прекаленото хранене.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Small open reading frames (smORF) as novel modulators of disorders of dietary excess

Dietary excess is a major driver of human modern diseases, including dyslipidemia and cardiovascular (CVD) diseases, the leader in the cause of mortality worldwide. The intestine plays a unique role in the metabolic defense against energy excess through regulation of dietary lipid uptake, lipoprotein production, and cholesterol excretion. The regulation of lipid metabolism in the intestine is very complex and is mediated by different genes. Recent studies have suggested that the regulation of this metabolism in the intestine could be also modulated by non-coding RNAs, specifically by small open reading frames (smORFs)-encoded peptides (SEP). However, whether the enterocyte produces specific smORF-encoded bioactive or regulatory peptide that regulates lipid metabolism remains completely obscure. In this sense, recent advances in bioinformatics, proteomics, and high-throughput analyses of translation start sites have begun to address these challenges and identified hundreds of putative coding smORFs and occasionally widely conserved. Indeed, the recent finding suggests that some SEPs or microproteins with a diverse physiological role in different species and human cells and tissues. All these findings provide strong evidence of the unanticipated complexity of our human small proteome. However, the contribution of their potential peptide products to cellular functions, if any, remains unknown. Thus, the discovery of novel intestinal players as microproteins, and a deeper insight into its biological function may contribute significantly to the understanding of modern human diseases and provide new opportunities to treat dyslipidemia and other deadly sequelae of dietary excess. In this context, the LIPMETIN-sURFing project and training program is designed to go beyond the state-of-the-art and will provide new data to 1) screen novel microproteins from intestine, 2) validate the presence of a selected novel microprotein and search for a biological function in lipid metabolism, and 3) evaluate whether the microproteins could be modulated by a food bioactive component.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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

Оригинален текст от CORDIS (на английски).

Участници

FUNDACIÓN IMDEA NUTRICIÓN · MADRIDКоординаторИспания
THE SALK INSTITUTE FOR BIOLOGICAL STUDIES · La JollaСъединени щати