MechanoGenetic · Role of mechanical forces in cell-matrix adhesion sites
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-11-01 → 2022-08-31
- Финансиране от ЕС
- 153 085 €
- Участници
- 1
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Механичните сили в местата на закрепване на мускулите към сухожилията се анализират чрез генетични мутации при плодови мухи. Разбирането на тези процеси помага за по-доброто справяне с дистрофичните заболявания при хората.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Role of mechanical forces in cell-matrix adhesion sites
Muscle cells in the human body often fail to work properly because their connections to the tendons become weak. This is a serious medical condition that can lead to skeletal myopathies. To design suitable therapies we need to discover the molecular and biophysical principles of how muscles build and maintain their muscle attachments. To this end, I implemented an interdisciplinary research combining the power of Drosophila genetics with appropriate biophysical tools and methods. This approach allowed me to model how specific mutations in conserved genes that encode proteins of the integrin adhesome weaken the myotendinous junctions in the fly embryo. Given the striking similarities in the molecular organisation of the myotendinous junctions between fly and human, the obtained data provide a novel mechanical framework of how muscle cells integrate forces and maintain tissue integrity in the living organism. Ultimately, the acquired knowledge obtained in this project provides a deeper understanding of how we can better combat dystrophic diseases.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Cells in our bodies constantly experience mechanical forces from their microenvironment. When cells sense a critical threshold of elevated tension, they hold tight together and allow tissues to function healthily as a group. In certain diseases, however, our cells lose their mechanosensing and adhesive properties and, as a result they get dissociated, as in the case of muscular dystrophies. Integrin-based adhesions to the extracellular matrix (ECM) are emerging as key networks of mechanotransmission. This proposal aims to discover how mechanical forces modulate cell-matrix adhesion at the myotendinous junctions in the developing Drosophila embryo, combining biophysical, molecular and genetic approaches. To achieve this goal, I propose to implement two complementary specific objectives: First, I will identify and quantify the relationship between forces and adhesion strength in mutants affecting either integrin-ECM binding or muscle contractility by utilizing in vivo laser ablation and magnetic tweezers. Second, I will examine whether and how IPP complex -a core module of the integrin adhesome- alters the molecular forces transmitted across Talin, which is a major mechanosensor at integrin junctions, utilizing suitable FRET-based biosensors. Collectively, this interdisciplinary research will provide a novel mechanical framework of how cells integrate forces and maintain tissue integrity in the living organism.Given the striking similarities in the molecular organisation of the myotendinous junctions between fly and human, the outcome of this work will provide a deeper understanding of how we can better combat dystrophic diseases.
Оригинален текст от CORDIS (на английски).
Участници
- IDRYMA IATROVIOLOGIKON EREUNON AKADEMIAS ATHINON · AthinaКоординаторГърция
Връзки
Данни: CORDIS, © Европейски съюз