H2020Индивидуална стипендия2018–2020

MetChromTx · Macrophage metabolism and signal-induced chromatin and transcription changes: an integrated, multi-layer approach

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

Период: 2018-10-01 → 2020-09-30
Финансиране от ЕС: 180 277 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Макрофагите, които са част от имунната система, се изследват, за да се разбере как метаболизмът им влияе върху генетичната им активност. Това помага за по-доброто разбиране на механизмите при рак и хронични възпалителни заболявания.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Macrophage metabolism and signal-induced chromatin and transcription changes: an integrated, multi-layer approach

Cells are special devices with the ability to integrate environmental signals. Prototypical example are macrophages, key components of the innate immune system, which are capable of reacting to environmental changes with distinct activities. Macrophages play key roles during homeostatic processes and immunity but are also involved in a variety of inflammatory diseases and cancers. As stated by the World Health Organization (WHO) chronic inflammatory diseases are the most significant cause of death in the world and macrophages are undoubtedly the major player. For these reasons a lot of effort has been invested in research studies aiming at better understanding macrophage biology and regulation. Nevertheless, the reciprocal influences that signal-induced transcriptional and metabolic changes have on one another have been overlooked. The action “Macrophage metabolism and signal-induced chromatin and transcription changes: an integrated, multi-layer approach” aims to unravel key mechanistic principles during macrophage activation and to develop computational approaches for the integration of “big-omics” datasets into interpretable models. The generation of predictive models is essential for basic research to become more exploitable. Specific objectives of this action have been to: (a) Relate transcriptional changes to metabolic pathways activation and assess the role of specific transcription factors (TFs) through model assembly. (b) Dissect the transcriptional effects driven by metabolic pathways focusing on specific key metabolites. Given the challenging task to both develop and perform bench experiments and use my computational expertise to integrate the generated datasets Insilco this action allowed the development and scientific growth of the researcher.

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

Цел на проекта

Organismal responses to environmental threats involve the activation of both resident and monocyte-derived macrophages, key components of the innate immune system. Macrophages are capable of rapidly sensing micro-environmental changes and of reacting with distinct activities ranging from specialised homeostatic functions, to the activation of effector functions in tissue immune surveillance. These diverse biological outcomes are brought about by the coordinated rewiring of both metabolic and transcriptional networks. Although much is known about the metabolic configuration and the transcriptional signatures of activated macrophages, their reciprocal influences have not been systematically investigated. Metabolic changes linked to acute activation are primarily, although not exclusively, driven by transcriptional changes; nevertheless, how these changes are coordinated and implemented over time remains unsolved. In addition, changes in metabolic state are accompanied by changes in metabolites availability, some of which are cofactors or co-substrates of chromatin-modifying enzymes, essential players in the control of gene expression. I aim to unravel key mechanistic principles on the interplay between transcriptional and metabolic control in macrophages by adopting two complementary approaches: (1) I will identify the complement of transcription factors controlling dynamic metabolic changes at different times during macrophage activation by combining genomic and metabolomic techniques; (2) I will characterise how metabolic pathways signal to specific enhancers thus eventually affecting inflammatory gene transcription and chromatin changes. This project will contribute to systematically dissect fundamental principles of integrated cell control in response to micro-environmental stimuli, advancing our understanding of the coordination between metabolic re-programming and gene transcriptional programs.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITA HUMANITAS · PIEVE EMANUELEКоординаторИталия