Systems biology of size control in eukaryotes
真核生物尺寸控制的系统生物学
基本信息
- 批准号:RGPIN-2020-06375
- 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:2021
- 资助国家:加拿大
- 起止时间:2021-01-01 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
In addition to be the fundamental unit of life, the cell is also the basic unit of growth. Understanding what regulates the overall growth of cell and how this is coordinated with progression of the cell cycle are longstanding problems in cell biology. During the last century, a major focus of cell biology has been the study of cell division, but how eukaryotic cells couple growth to division to maintain a homeostatic size remains poorly understood. Cell size of a microorganism is influenced by the quality and the quantity of nutrients in the surrounding environment. For instance, yeast cells growing in the presence of their optimal carbon source, glucose, are larger than cells growing in ethanol or glycerol as a sole source of carbon. This emphasizes an intimate link between the machinery that sense the nutritional status of the environment and the mechanism that coordinate growth and division and consequently cell size. Many studies have shown that transcriptional networks and signaling pathways have been subjected to numerous evolutionary changes in the budding yeast Saccharomyces cerevisiae as compared to other species. Thus, despite its preeminent role as a genetically tractable model system, insights gained into cell size control mechanisms in S. cerevisiae may not be generalizable. Indeed, our systematic screen for size mutants in the opportunistic yeast Candida albicans revealed a divergence of central regulators, such as the MAPK module HOG/p38, consistent with an evolutionary plasticity of the size control network. The goal of this research program is to understand how Hog1 modulates cell size and what are the upstream signals sensed by this pathway to preserve size homeostasis (AIM #1). Interestingly, we have shown that the role of some of those size genes such as the Hog1/p38s were also conserved in humans. Thus, we will test the hypothesis that other conserved genes that affect size in C. albicans may also modulate size in human cells (AIM #2). A central question in size control is how the size threshold adapts to environmental variation. It has been argued that optimization of organism size is a dominant evolutionary force because fitness depends exquisitely on adaptation to a particular size niche. The strong link between size and fitness has been elegantly demonstrated through the artificial evolution of E. coli strains adapted to different growth rates. Here, we seek to delineate the nutrient-dependent size control machinery in C. albicans. We expect that this study will provide fundamental insights into mechanisms of eukaryotic cell cycle commitment (AIM #3). The proposed studies will generate extensive datasets and hypothesis suitable for HQP training and for further in-depth investigations supported by a variety of other competitive funding agencies.
除了是生命的基本单位,细胞也是生长的基本单位。了解是什么调节细胞的整体生长以及如何与细胞周期的进展协调是细胞生物学中长期存在的问题。在上个世纪,细胞生物学的一个主要焦点是细胞分裂的研究,但真核细胞如何将生长与分裂耦合以维持稳态大小仍然知之甚少。微生物的细胞大小受周围环境中营养物质的质量和数量的影响。例如,在最佳碳源葡萄糖存在下生长的酵母细胞比在作为唯一碳源的乙醇或甘油中生长的细胞大。这强调了感知环境营养状况的机制与协调生长和分裂以及细胞大小的机制之间的密切联系。许多研究表明,与其他物种相比,芽殖酵母酿酒酵母的转录网络和信号通路发生了许多进化变化。因此,尽管它作为一个遗传学上易处理的模型系统的卓越作用,在S.酿酒酵母可能无法推广。事实上,我们的系统性筛选的机会性酵母菌白色念珠菌的大小突变体揭示了中央监管机构,如MAPK模块HOG/p38的分歧,符合进化可塑性的大小控制网络。 这项研究计划的目标是了解Hog 1如何调节细胞大小,以及该途径感知的上游信号是什么,以保持大小稳态(AIM #1)。有趣的是,我们已经证明了一些大小基因的作用,如Hog 1/p38在人类中也是保守的。因此,我们将测试的假设,其他保守的基因,影响大小在C。白色念珠菌也可以调节人细胞的大小(AIM#2)。尺寸控制的一个中心问题是尺寸阈值如何适应环境变化。有人认为,生物体大小的优化是一种占主导地位的进化力量,因为适应性取决于对特定大小生态位的适应。大小和适合度之间的紧密联系已经通过E.大肠杆菌菌株适应不同的生长速率。在这里,我们试图描绘C.白色念珠菌我们期望这项研究将为真核细胞周期定型(AIM #3)的机制提供基本的见解。拟议的研究将产生广泛的数据集和假设,适用于HQP培训和其他各种竞争性资助机构支持的进一步深入调查。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Sellam, Adnane其他文献
A toolbox for epitope-tagging and genome-wide location analysis in Candida albicans
- DOI:
10.1186/1471-2164-9-578 - 发表时间:
2008-12-02 - 期刊:
- 影响因子:4.4
- 作者:
Lavoie, Hugo;Sellam, Adnane;Whiteway, Malcolm - 通讯作者:
Whiteway, Malcolm
Transcriptome Analysis Uncovers a Link Between Copper Metabolism, and Both Fungal Fitness and Antifungal Sensitivity in the Opportunistic Yeast Candida albicans
- DOI:
10.3389/fmicb.2020.00935 - 发表时间:
2020-05-19 - 期刊:
- 影响因子:5.2
- 作者:
Khemiri, Ines;Tebbji, Faiza;Sellam, Adnane - 通讯作者:
Sellam, Adnane
Metabolic Reprogramming in the Opportunistic Yeast Candida albicans in Response to Hypoxia
- DOI:
10.1128/msphere.00913-19 - 发表时间:
2020-01-01 - 期刊:
- 影响因子:4.8
- 作者:
Burgain, Anais;Tebbji, Faiza;Sellam, Adnane - 通讯作者:
Sellam, Adnane
The zinc cluster transcription factor Ahr1p directs Mcm1p regulation of Candida albicans adhesion
- DOI:
10.1111/j.1365-2958.2010.07504.x - 发表时间:
2011-02-01 - 期刊:
- 影响因子:3.6
- 作者:
Askew, Christopher;Sellam, Adnane;Whiteway, Malcolm - 通讯作者:
Whiteway, Malcolm
Role of Ndt80p in Sterol Metabolism Regulation and Azole Resistance in Candida albicans
- DOI:
10.1128/ec.00074-09 - 发表时间:
2009-08-01 - 期刊:
- 影响因子:0
- 作者:
Sellam, Adnane;Tebbji, Faiza;Nantel, Andre - 通讯作者:
Nantel, Andre
Sellam, Adnane的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Sellam, Adnane', 18)}}的其他基金
Systems biology of size control in eukaryotes
真核生物尺寸控制的系统生物学
- 批准号:
RGPIN-2020-06375 - 财政年份:2022
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Systems biology of size control in eukaryotes
真核生物尺寸控制的系统生物学
- 批准号:
RGPIN-2020-06375 - 财政年份:2020
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Systems Biology of the hypoxic adaptation
缺氧适应的系统生物学
- 批准号:
RGPIN-2014-06625 - 财政年份:2019
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Systems Biology of the hypoxic adaptation
缺氧适应的系统生物学
- 批准号:
RGPIN-2014-06625 - 财政年份:2018
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Systems Biology of the hypoxic adaptation
缺氧适应的系统生物学
- 批准号:
RGPIN-2014-06625 - 财政年份:2017
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Systems Biology of the hypoxic adaptation
缺氧适应的系统生物学
- 批准号:
RGPIN-2014-06625 - 财政年份:2016
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Systems Biology of the hypoxic adaptation
缺氧适应的系统生物学
- 批准号:
RGPIN-2014-06625 - 财政年份:2015
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Systems Biology of the hypoxic adaptation
缺氧适应的系统生物学
- 批准号:
RGPIN-2014-06625 - 财政年份:2014
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
相似国自然基金
组蛋白乙酰化修饰ATG13激活自噬在牵张应力介导骨缝Gli1+干细胞成骨中的机制研究
- 批准号:82370988
- 批准年份:2023
- 资助金额:48.00 万元
- 项目类别:面上项目
Journal of Integrative Plant Biology
- 批准号:31024801
- 批准年份:2010
- 资助金额:24.0 万元
- 项目类别:专项基金项目
Computational Methods for Analyzing Toponome Data
- 批准号:60601030
- 批准年份:2006
- 资助金额:17.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Systems biology of size control in eukaryotes
真核生物尺寸控制的系统生物学
- 批准号:
RGPIN-2020-06375 - 财政年份:2022
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Developing Nanoparticle Drug Delivery Systems for Venous Malformations
开发治疗静脉畸形的纳米颗粒药物输送系统
- 批准号:
10668483 - 财政年份:2022
- 资助金额:
$ 2.62万 - 项目类别:
Developing Nanoparticle Drug Delivery Systems for Venous Malformations
开发治疗静脉畸形的纳米颗粒药物输送系统
- 批准号:
10525714 - 财政年份:2022
- 资助金额:
$ 2.62万 - 项目类别:
Systems analysis of mechanisms driving response to immunotherapy in clear cell cancers
透明细胞癌免疫疗法驱动反应机制的系统分析
- 批准号:
10554766 - 财政年份:2022
- 资助金额:
$ 2.62万 - 项目类别:
Systems analysis of mechanisms driving response to immunotherapy in clear cell cancers
透明细胞癌免疫疗法驱动反应机制的系统分析
- 批准号:
10704140 - 财政年份:2022
- 资助金额:
$ 2.62万 - 项目类别: