MTUB-ANGIO · Microtubule Dynamics during angiogenesis
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2016-09-01 → 2018-08-31
- Финансиране от ЕС
- 177 599 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Микротрубулите в ендотелните клетки определят как се формират новите кръвоносни съдове. Разбирането на този процес помага за по-доброто проучване на развитието на туморите и подобряването на противораковата терапия.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Microtubule Dynamics during angiogenesis
Angiogenesis is a decisive process through which new blood vessels emerge and develop from a pre-existing vasculature. This dynamic process requires that the endothelial cells, the cells that line our blood vessels, undergo profound shape changes and reorganize their scaffolding cytoskeleton. The microtubule network is precisely one of the main cytoskeletal elements of eukaryotic cells, but surprisingly the role of microtubules during angiogenesis remains poorly characterized. As angiogenesis is a process that plays crucial roles in physiology and pathology, especially during cancer development because tumor progression crucially need blood vessel recruitment, a better understanding of the regulation of angiogenesis constitutes an important health research area. Microtubules are particularly interesting to study in this context because targeting them is one of most frequently used anticancer treatment. In order to extend our knowledge on the cellular mechanisms underlying microtubule regulation and function during angiogenesis, we wanted to address the role of microtubule regulatory proteins using advanced live imaging of 3D culture of endothelial cells mimicking angiogenesis. Very interestingly, by setting-up such an approach, we found that microtubule organization and dynamics are crucial for the endothelial cells to sprout properly and build a functional vessel network. We particularly studied two aspects of microtubule: their processive growth and the symmetry of the network they are building. We assessed the role of these microtubule properties by identifying important regulators and showing their decisive angiogenic role after interfering with their function. By validating some results in vivo using zebrafish, we established a previously unexpected role for the organisation of the microtubule network in the regulation of angiogenesis.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Restoring normal vessel structure and function is now considered as a highly promising therapeutic opportunity for angiogenesis-related diseases, including cancer. Despite extensive use of microtubule targeting compounds in vascular-directed anticancer treatment, knowledge of the cellular mechanisms underlying microtubule regulation during angiogenesis is still elusive. By combining my previous experience in endothelial cell biology and the long term expertise of the host laboratory in microtubules dynamics as well as in high resolution imaging techniques, our project is aimed at studying microtubule dynamics and microtubule function in the precise context of sprouting angiogenesis. To achieve that goal, we propose to address the role of microtubule regulatory proteins using advanced high resolution live imaging of 3D culture of endothelial cells. We will identify endothelial specific MT regulators through expression, interaction and functional studies, assess their impact on microtubule dynamics during 3D tubulogenesis and validate their role both in the 3D morphogenesis model and in vivo, using zebrafish. This project is aimed at answering fundamental questions in the angiogenesis field as well as providing new opportunities for therapeutic strategies. At the same time, my experience in the laboratory of Dr Akhmanova will allow me to develop knowledge and skills in order to prepare me to reach a position of professional maturity.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITEIT UTRECHT · UtrechtКоординаторНидерландия
Връзки
Данни: CORDIS, © Европейски съюз
