Exploring extracellular matrix remodelling during lung branching morphogenesis
探索肺分支形态发生过程中的细胞外基质重塑
基本信息
- 批准号:RGPIN-2018-05599
- 负责人:
- 金额:$ 2.62万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2020
- 资助国家:加拿大
- 起止时间:2020-01-01 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Formation of the lung is an important process required for survival. Our research is focused on understanding how cells function during lung development and how this function is controlled. Cells within any tissue are surrounded by a “scaffold” of proteins called the extracellular matrix. This scaffold is not a static structure and is constantly being changed or remodelled by removing and adding different proteins. Importantly, this scaffold has the ability to signal to cells. This signalling can occur through direct interaction between the scaffold and the cells, as well as by the scaffold binding to and releasing specific signalling proteins called growth factors. My previous work found that when one of the proteins within the scaffold (called fibronectin) is altered, the formation of the lung airways is impaired because the cells within the airway do not divide (or proliferate) appropriately. Therefore, our proposed studies are focused on understanding how this entire scaffold is changed during lung development and how changes to the scaffold alters lung development.
To do this, my lab will initially examine how the scaffold is changed (i.e. how proteins are deposited or removed) during formation of the airways. Lungs will be isolated from developing mice and we will look at the expression of genes associated with the scaffold and how these genes change. We will also use a new technique, called TAILS, that allows us to identify the proteins within the lung that are being changed, specifically degraded or cleaved by enzymes. Our long term goal will be to determine how changes to the scaffold change airway formation. For this, we will use a model of lung development where the scaffold appears to be changed and examine how these changes alter lung development. These studies will allow us to identify how the scaffold, and importantly, changes to the scaffold, control cell function during lung development, specifically during airway formation.
Overall, our work will identify new ways through which essential cellular functions are controlled in the developing lung by the surrounding scaffold or matrix. Importantly, there is similarity with how cells are controlled in many different developing organs. Thus, in addition to identifying specific factors that control lung development, our studies will address concepts that are important for the development of many different organs.
肺的形成是生存所需的重要过程。我们的研究重点是了解细胞在肺发育过程中的功能以及这种功能是如何控制的。任何组织内的细胞都被称为细胞外基质的蛋白质“支架”包围。这个支架不是一个静态的结构,并且通过去除和添加不同的蛋白质而不断改变或重塑。重要的是,这种支架具有向细胞发出信号的能力。这种信号传导可以通过支架和细胞之间的直接相互作用发生,也可以通过支架结合并释放称为生长因子的特定信号蛋白发生。我以前的工作发现,当支架内的一种蛋白质(称为纤连蛋白)被改变时,肺气道的形成就会受损,因为气道内的细胞不能适当地分裂(或增殖)。因此,我们提出的研究重点是了解整个支架在肺发育过程中是如何变化的,以及支架的变化如何改变肺发育。
为了做到这一点,我的实验室将首先检查支架在气道形成过程中是如何变化的(即蛋白质是如何沉积或去除的)。肺将从发育中的小鼠中分离出来,我们将观察与支架相关的基因的表达以及这些基因如何变化。我们还将使用一种名为TAILS的新技术,该技术使我们能够识别肺内正在发生变化的蛋白质,特别是被酶降解或切割的蛋白质。我们的长期目标将是确定支架的变化如何改变气道形成。为此,我们将使用肺发育模型,其中支架似乎发生了变化,并检查这些变化如何改变肺发育。这些研究将使我们能够确定支架,重要的是,支架的变化,在肺发育过程中控制细胞功能,特别是在气道形成过程中。
总的来说,我们的工作将确定新的方式,通过这些方式,基本细胞功能在发育中的肺中由周围的支架或基质控制。重要的是,在许多不同的发育器官中,细胞是如何被控制的。因此,除了确定控制肺发育的特定因素外,我们的研究还将解决对许多不同器官发育重要的概念。
项目成果
期刊论文数量(0)
专著数量(0)
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Gill, Sean其他文献
Rapid priority setting exercise on faecal incontinence for Cochrane Incontinence.
- DOI:
10.1136/bmjgast-2021-000847 - 发表时间:
2022-05 - 期刊:
- 影响因子:3.1
- 作者:
Thomson, Katie H.;O'Connor, Nicole;Dangova, Kim Tuyen;Gill, Sean;Jackson, Sara;Bliss, Donna Z.;Wallace, Sheila A.;Pearson, Fiona - 通讯作者:
Pearson, Fiona
Biomechanically constrained groupwise ultrasound to CT registration of the lumbar spine
- DOI:
10.1016/j.media.2010.07.008 - 发表时间:
2012-04-01 - 期刊:
- 影响因子:10.9
- 作者:
Gill, Sean;Abolmaesumi, Purang;Mousavi, Parvin - 通讯作者:
Mousavi, Parvin
Proteoglycans: key regulators of pulmonary inflammation and the innate immune response to lung infection.
- DOI:
10.1002/ar.21094 - 发表时间:
2010-06 - 期刊:
- 影响因子:2
- 作者:
Gill, Sean;Wight, Thomas N.;Frevert, Charles W. - 通讯作者:
Frevert, Charles W.
Gill, Sean的其他文献
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{{ truncateString('Gill, Sean', 18)}}的其他基金
Exploring extracellular matrix remodelling during lung branching morphogenesis
探索肺分支形态发生过程中的细胞外基质重塑
- 批准号:
RGPIN-2018-05599 - 财政年份:2022
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Exploring extracellular matrix remodelling during lung branching morphogenesis
探索肺分支形态发生过程中的细胞外基质重塑
- 批准号:
RGPIN-2018-05599 - 财政年份:2021
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Exploring extracellular matrix remodelling during lung branching morphogenesis
探索肺分支形态发生过程中的细胞外基质重塑
- 批准号:
RGPIN-2018-05599 - 财政年份:2019
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Exploring extracellular matrix remodelling during lung branching morphogenesis
探索肺分支形态发生过程中的细胞外基质重塑
- 批准号:
RGPIN-2018-05599 - 财政年份:2018
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Exploring extracellular matrix remodelling during lung branching morphogenesis
探索肺分支形态发生过程中的细胞外基质重塑
- 批准号:
RGPIN-2017-05573 - 财政年份:2017
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
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RGPIN-2017-05573 - 财政年份:2017
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual