H2020Индивидуална стипендия2020–2023

RegADyn · In vivo characterization of novel actin dynamic regulators during cell migration

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

Период: 2020-06-01 → 2023-05-31
Финансиране от ЕС: 295 062 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Генни регулатори на актина се изследват в ембриони на зебериш, за да се разбере как клетките променят формата си и завиват при движение. Това помага да се обяснят процеси като развитието на плода, заздравяването на рани и разпространението на метастази при рак.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

In vivo characterization of novel actin dynamic regulators during cell migration

The overall scientifc goal of the Regadyn project carried out by the fellow Sophie Escot is to better understand the molecular machinery that control the ability of cells to migrate. Cell migration is a critical process for embryogenesis, defective migration being the basis of numerous developmental disorders. During adult life, migration is key to immune cell function and wound healing. Furthermore, acquisition of migratory properties by tumour cells triggers the formation of metastases, which is the most dreadful event during cancer progression. To migrate, most cells rely on an internal skeleton (termed cytoskeleton), and mostly on one of its constituents, actin, which can be rapidly remodeled, to deform the cell, and allow it to move. Controlling the dynamics of actin is thus key in controlling cell migration. While the major molecular pathway controlling actin dynamics has been identified, it is now clear that this pathway is precisely fine-tuned, with many intricated feedback loops defining its properties. These feedback loops, by controlling actin dynamics in term control the speed of cell migration, but maybe more importantly, its directionality (the ability of cells to turn). The aim of the project was to characterize the in vivo function of the three candidate genes we had identified as potentially involved in these feedback loops. This in vivo characterization was performed in early zebrafish embryos, as it is close enough to human for the mechanisms to be conserved, it allows direct observation of cell migration in the intact living embryo, it allows easy genetic manipulations. The Regadyn project is Career Restart project. Scientific knowledge is both complex and fast evolving. While it may take years for a researcher to acquire the knowledge, skills and technical tools to be able to produce original results, a one-year hiatus may be enough to be largely overtaken by the competition. This inability to stop for a while is a major handicap in building a career, especially for women who wish to have children. The aim of this project was to allow me to restart an academic career after a 15-month break to raise my child.

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

Цел на проекта

Cell migration is a critical process for embryogenesis, immune cell function and wound healing as well as cancer progression. Most normal cells migrate by protruding the plasma membrane forward through actin polymerization. The formation of a protrusion requires activation of the small GTPase Rac1 that in turn activates the WAVE complex, which induces branched actin networks through the Arp2/3 complex. For efficient cell migration, membrane protrusion at the leading edge must be sustained. Conversely, cells need to retract membrane protrusion to stop cell migration or turn. The tight control of protrusion lifetime and directional persistence is thus critical to fine tune cell migration. At the molecular level, persistence is controlled by positive and negative feedback loops. However, only few of these feedback loops have been identified and almost none has been characterized, in particular in vivo. In a joint effort with two other labs, proteomic screens were used to identify proteins that interact with the WAVE complex and whose interaction is modulated by branched actin. Based on different selection criteria such as their role in actin dynamics in vitro, conservation in fish, and absence of in vivo data, I selected three candidates. I will unravel their in vivo function at different scales, from embryonic development, to cell migration, to membrane protrusion and cytoskeleton dynamics. Actin feedback loops regulating cell migration will be specifically dissected. To do so, I will take advantage of two complementary and well characterized cellular models: endodermal cells and prechordal plate cells. Endodermal cells perform a random walk, while prechordal plate cells exhibit a directed collective migration. This project, which relies on validated unbiased screens and well established cellular models and approaches, will provide new insights in our understanding of actin dynamics regulation and mechanisms that fine tune cell migration.

Оригинален текст от CORDIS (на английски).

Участници

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