20-BBSRC/NSF-BIO: Synthetic Control of Pattern Formation and Morphogenesis in a Purposefully Rewired Vertebrate Cell

20-BBSRC/NSF-BIO：有目的地重新连接的脊椎动物细胞中模式形成和形态发生的综合控制

基本信息

批准号：
BB/W013614/1
负责人：
Andrew Goryachev
金额：
$ 51.02万
依托单位：
University of Edinburgh
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FW013614%2F1
关键词：
20 BBSRC NSF BIO Synthetic

项目摘要

The cell cortex is responsible for responding to a variety of internal and external signals with the appropriate mechanical behavior. Such behaviors include cell division, cell locomotion and short or long-term cell shape changes. We and others have recently discovered a dynamical process-cortical excitability-that a variety of cell types harness to drive distinct mechanical behaviors. Cortical excitability is outwardly manifest as propagating cortical waves of actin assembly and complementary waves of the various macromolecules that control actin assembly. Cortical excitability is itself controlled by coupled fast positive feedback and delayed negative feedback. We will develop the means to synthetically induce cortical excitability in cells that do not normally display it, namely, frog oocytes, and employ high-resolution live cell imaging to capture the detailed features of excitability. The induction will be based on synthetic protein constructs engineered to produce either fast positive feedback or delayed negative feedback. By combining different synthetic constructs, we will drive simple cell shape changes (i.e., furrowing) or complex cell shape changes (i.e., gastrulation), allowing us to test basic ideas about cell shape control. In addition, by iteratively combining experiments with computational modeling, it will be possible to develop both a quantitative, mechanistic understanding of processes such as cell division and morphogenesis.

细胞皮层负责以适当的机械行为响应各种内部和外部信号。这种行为包括细胞分裂，细胞运动和短期或长期细胞形状变化。我们和其他人最近发现了动力学过程的兴奋性 - 各种细胞类型都可以驱动不同的机械行为。皮质兴奋性在外部表现为肌动蛋白组装的繁殖皮层波和控制肌动蛋白组装的各种大分子的互补波。皮质兴奋性本身由耦合的快速积极反馈和延迟的负反馈控制。我们将开发一种方法，以合成在通常不会显示的细胞中诱导皮质兴奋性，即青蛙卵母细胞，并采用高分辨率的活细胞成像以捕获兴奋性的详细特征。该诱导将基于设计的合成蛋白构建体，该蛋白质构建体，用于产生快速的正反馈或延迟的负反馈。通过结合不同的合成构建体，我们将驱动简单的细胞形状变化（即皱纹）或复杂的细胞形状变化（即胃肠道），从而使我们能够测试有关细胞形状控制的基本思想。此外，通过迭代地将实验与计算建模相结合，可以既有可能对细胞分裂和形态发生等过程进行定量的机械理解。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Microtubule detyrosination drives symmetry breaking to polarize cells for directed cell migration.

DOI：
10.1073/pnas.2300322120
发表时间：
2023-05-30
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Lavrsen, Kirstine;Rajendraprasad, Girish;Leda, Marcin;Eibes, Susana;Vitiello, Elisa;Katopodis, Vasileios;Goryachev, Andrew B.;Barisic, Marin
通讯作者：
Barisic, Marin

Publisher Correction: Patterning of the cell cortex by Rho GTPases.

出版商更正：Rho GTPases 对细胞皮层的图案化。