Inter-organ signals regulating body size, physiology anddevelopmental timing

调节身体大小、生理和发育时间的器官间信号

基本信息

批准号：
10629351
负责人：
MICHAEL Brendan O'CONNOR
金额：
$ 38.05万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2026-05-31
项目状态：
未结题

项目摘要

Inter-organ signals that regulate body size, physiology and developmental timing Identifying and characterizing physiologic mechanisms that regulate organ communication and function during development and adulthood is vital for understanding how many important human health problems arise and intensify during our lifetimes. This proposal outlines a research strategy to further characterize key signaling systems that regulate critical and conserved physiological processes. These include determining how a signaling network of three Drosophila Activin-like members of the TGF-beta superfamily coordinately control fundamental aspects of brain, muscle, and fatbody cellular function in response to environmental variables such as nutrition during development to maintain physiologic homeostasis and how neuroendocrine mechanisms regulate steroid production and release, also in response to various internal and external cues, to properly time developmental maturation. We will use a wide variety of modern biological investigative methods including genetic analysis, neuronal circuit and activity mapping, biochemistry, optical/EM imaging, metabolomics, temporal and tissue specific transcriptome characterization as well as chromatin immunoprecipitation experiments, to answer these questions. Impact on human health: The successful completion of these aims will provide novel insight into how an two very conserved inter-organ signaling networks parse out specific, as well as combinatorial control, over various fundamental cellular processes to produce a properly proportioned animal, that is optimized for survival in its particular ecological niche. It is expected that this knowledge will provide useful paradigms for understanding functional aspects of the more complex, but highly related vertebrate TGF-beta and neuroendocrine signaling systems, and will afford novel insights into molecular mechanisms that contribute to a number of human disorders including obesity, metabolic syndrome, muscle wasting, pubertal disorders and ageing.

调节身体大小、生理和发育时间的器官间信号识别和表征调节器官的生理机制发育和成年期间的沟通和功能对于理解至关重要在我们的一生中，有多少重要的人类健康问题出现并加剧。该提案概述了进一步表征关键信号系统的研究策略调节关键和保守的生理过程。这些包括确定 TGF-β 的三个果蝇激活素样成员的信号网络如何超家族协调控制大脑、肌肉和脂肪体的基本方面细胞功能对环境变量（例如营养）的反应发育维持生理稳态以及神经内分泌机制如何调节类固醇的产生和释放，也响应各种内部和外部的线索，以适当地安排发育成熟的时间。我们将使用各种各样的现代生物研究方法，包括遗传分析、神经元回路和活动绘图、生物化学、光学/电磁成像、代谢组学、时间和组织特异性转录组表征以及染色质免疫沉淀实验，回答这些问题。对人类健康的影响：成功完成这些目标将为了解两个非常保守的器官间信号传导如何提供新的见解网络解析出对各种基本的特定的以及组合的控制细胞过程产生适当比例的动物，这是优化的在其特定的生态位中生存。预计这些知识将提供用于理解更复杂但高度复杂的功能方面的有用范例相关的脊椎动物 TGF-β 和神经内分泌信号系统，并将提供新颖的对导致许多人类疾病的分子机制的见解包括肥胖、代谢综合征、肌肉萎缩、青春期疾病和衰老。

项目成果

期刊论文数量（29）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The cytochrome P450 Cyp6t3 is not required for ecdysone biosynthesis in Drosophila melanogaster.

DOI：
10.17912/micropub.biology.000611
发表时间：
2022
期刊：
microPublication biology
影响因子：
0
作者：
Shimell, MaryJane;O'Connor, Michael B
通讯作者：
O'Connor, Michael B

A juxtamembrane basolateral targeting motif regulates signaling through a TGF-β pathway receptor in Drosophila.

DOI：
10.1371/journal.pbio.3001660
发表时间：
2022-05
期刊：
PLoS biology
影响因子：
9.8
作者：
通讯作者：

Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size.

DOI：
10.1016/j.celrep.2021.109644
发表时间：
2021-08-31
期刊：
Cell reports
影响因子：
8.8
作者：
Pan X;O'Connor MB
通讯作者：
O'Connor MB

Regulation of Drosophila hematopoietic sites by Activin-β from active sensory neurons.

DOI：
10.1038/ncomms15990
发表时间：
2017-07-27
期刊：
Nature communications
影响因子：
16.6
作者：
Makhijani K;Alexander B;Rao D;Petraki S;Herboso L;Kukar K;Batool I;Wachner S;Gold KS;Wong C;O'Connor MB;Brückner K
通讯作者：
Brückner K

Glue protein production can be triggered by steroid hormone signaling independent of the developmental program in Drosophila melanogaster.