Dynamic decisions: Integrating dynamic gene expression with mechanical signals to understand retinogenesis and ocular disorders.
动态决策:将动态基因表达与机械信号相结合,以了解视网膜发生和眼部疾病。
基本信息
- 批准号:MR/V032534/1
- 负责人:
- 金额:$ 166.07万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Fellowship
- 财政年份:2021
- 资助国家:英国
- 起止时间:2021 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
The growth of an organ is a complex process that needs to be tightly controlled to ensure that structures in the body are correctly organised. Groups of cells must co-ordinate moving and changing shape with decisions to proliferate or specialise into mature cell types of the adult organ. My recent work has shown that during organ growth, genes are not simply on or off. Instead, the levels of some genes pulse dynamically over time, and this helps control whether cells decide to proliferate or specialise. It is not clear how changes in cell shape, tissue folding and mechanics are co-ordinated with the pulses in gene activity during cell decisions. This is particularly important in embryonic eye development and growth. Genetic changes in certain proteins which sense forces and tissue mechanics can lead to the eye disorders coloboma and microphthalmia. These eye disorders occur when the sequence of developmental steps in the growth of an eye in the womb are disrupted. Children born with microphthalmia have small under-developed eyes. Those with coloboma have a cleft or hole in one or more structures of the eye, such as the retina. These conditions affect vision, and there are currently no treatments. That coloboma, a structural tissue disorder, and microphthalmia, a disorder of cellular decisions, occur together suggests a two-way link between tissue mechanics and cell decisions. I will investigate how, within the developing eye, forces from tissue folding and movement affect cell fate gene activity over time. I will use state-of-the-art live imaging techniques that show gene activity in real time. I will introduce the genetic changes seen in coloboma and microphthalmia patients into 'mini-eyes' grown in a dish to investigate how these disorders occur. Understanding the links between mechanical signals and cell decisions will support development of innovative cell-based therapies. My work therefore has important implications for furthering understanding of developmental ocular disorders and innovative regenerative medicine approaches.
器官的生长是一个复杂的过程,需要严格控制,以确保身体结构的正确组织。细胞群必须协调移动和改变形状,决定增殖或特化成成年器官的成熟细胞类型。我最近的研究表明,在器官生长过程中,基因并不是简单的开或关。相反,一些基因的水平随着时间的推移而动态变化,这有助于控制细胞是决定增殖还是专门化。目前还不清楚细胞形状、组织折叠和力学的变化是如何与细胞决定过程中基因活动的脉冲协调一致的。这在胚胎眼的发育和生长中尤为重要。感知力量和组织力学的某些蛋白质的遗传变化可导致眼部疾病结肠瘤和小眼症。当子宫内眼睛生长的发育步骤被打乱时,就会发生这些眼部疾病。患有小眼症的儿童眼睛很小,发育不全。那些患有结肠瘤的人在眼睛的一个或多个结构上有一个裂缝或洞,比如视网膜。这些情况会影响视力,目前还没有治疗方法。结肠瘤(一种结构性组织紊乱)和小眼症(一种细胞决策紊乱)同时发生,表明组织力学和细胞决策之间存在双向联系。我将研究在发育中的眼睛中,组织折叠和运动的力量如何随着时间的推移影响细胞命运和基因活动。我将使用最先进的实时成像技术实时显示基因活动。我将把结肠瘤和小眼患者的基因变化引入培养皿中培养的“迷你眼睛”中,以研究这些疾病是如何发生的。了解机械信号和细胞决策之间的联系将有助于创新细胞疗法的发展。因此,我的工作对进一步理解发育性眼部疾病和创新的再生医学方法具有重要意义。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Sequential and additive expression of miR-9 precursors control timing of neurogenesis.
- DOI:10.1242/dev.200474
- 发表时间:2022-10-01
- 期刊:
- 影响因子:0
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Cerys Manning其他文献
Localized and reversible TGFβ signalling switches breast cancer cells from cohesive to single cell motility
局部化且可逆的转化生长因子β信号将乳腺癌细胞从黏附状态转换为单细胞运动状态
- DOI:
10.1038/ncb1973 - 发表时间:
2009-10-18 - 期刊:
- 影响因子:19.100
- 作者:
Silvia Giampieri;Cerys Manning;Steven Hooper;Louise Jones;Caroline S. Hill;Erik Sahai - 通讯作者:
Erik Sahai
Cerys Manning的其他文献
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