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The systems biology of network stress based on data generated from in vitro differentiated hepatocytes from individual-specific human iPS cells

基于个体特异性人类 iPS 细胞体外分化肝细胞生成数据的网络压力系统生物学

基本信息

批准号：
BB/I004688/1
负责人：
Hans Westerhoff
金额：
$ 33.76万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FI004688%2F1
关键词：
systems biology network stress based

项目摘要

Our liver is the major chemical factory of our body. It removes unwelcome chemical compounds from our body, often after changing them chemically. The catch 22 situation here is that this function of the liver is good for the rest of the body, but potentially bad for the liver itself: during the chemical removal processes, toxic compounds tend to arise that put the liver under even more stress than already produced by the increased work load of the removal of the unwelcome compounds. A major hurdle in understanding how the liver deals with such stresses, has been the difference between human individuals. Due to this difference the response measured in one individual could not be used to predict the response to the stress in a different individual. Individuals differ in a limited but substantial number of small mutations in their DNA, some of which give rise alterations in molecular function of a number of molecules in the body. It has been impossible to relate differences in the response to stress, back to differences in any one of the mutated molecules. As in human societies, processes in living cells are carried out not by individuals but by networks of individuals. This project will therefore try to relate the response to stress of individuals not to their molecules but to their molecular networks. This will be done by a combination of experimentation with ultra modern experimental methods such as deep sequencing and mathematical modelling using fast and well-programmed computers. One result will be a mathematical model that describes part of the function of the liver and hence of the human.

肝脏是我们身体的主要化学工厂。它从我们的身体中去除不受欢迎的化学化合物，通常是在化学改变它们之后。第22条军规的情况是，肝脏的这种功能对身体的其他部分是好的，但对肝脏本身可能是坏的：在化学物质清除过程中，有毒化合物往往会出现，使肝脏承受比清除不受欢迎的化合物的工作量增加所产生的更大的压力。理解肝脏如何处理这种压力的一个主要障碍是人类个体之间的差异。由于这种差异，在一个个体中测量的反应不能用于预测不同个体对压力的反应。个体的差异在于其DNA中有限但大量的小突变，其中一些突变引起体内许多分子的分子功能改变。我们不可能把对压力反应的差异与任何一种突变分子的差异联系起来。与人类社会一样，活细胞中的过程不是由个人而是由个人网络进行的。因此，本项目将尝试将个体对压力的反应与其分子无关，而是与其分子网络有关。这将通过实验与超现代实验方法的结合来完成，例如使用快速和编程良好的计算机进行深度测序和数学建模。结果之一将是一个数学模型，描述肝脏的部分功能，从而描述人类的功能。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Targeting pathogen metabolism without collateral damage to the host.

DOI：
10.1038/srep40406
发表时间：
2017-01-13
期刊：
Scientific reports
影响因子：
4.6
作者：
Haanstra JR;Gerding A;Dolga AM;Sorgdrager FJH;Buist-Homan M;du Toit F;Faber KN;Holzhütter HG;Szöör B;Matthews KR;Snoep JL;Westerhoff HV;Bakker BM
通讯作者：
Bakker BM

Systems biology of HIF metabolism in cancer

DOI：
发表时间：
2012-10
期刊：
Mutagenesis
影响因子：
2.7
作者：
Emily G. Armitage;H. Westerhoff;Helen L. Kotze;R. Goodacre;N. Lockyer;K. Williams
通讯作者：
Emily G. Armitage;H. Westerhoff;Helen L. Kotze;R. Goodacre;N. Lockyer;K. Williams

Engineering of self-sustaining systems: Substituting the yeast glucose transporter plus hexokinase for the Lactococcus lactis phosphotransferase system in a Lactococcus lactis network in silico

DOI：
10.1002/biot.201100314
发表时间：
2012-07-01
期刊：
BIOTECHNOLOGY JOURNAL
影响因子：
4.7
作者：
Adamczyk, Malgorzata;Westerhoff, Hans V.
通讯作者：
Westerhoff, Hans V.

Systems biology of chemotherapy in hypoxia environments

DOI：
发表时间：
2012-11
期刊：
Mutagenesis
影响因子：
2.7
作者：
Helen L. Kotze;H. Westerhoff;N. Lockyer;R. Goodacre;Emily G. Armitage;K. Williams
通讯作者：
Helen L. Kotze;H. Westerhoff;N. Lockyer;R. Goodacre;Emily G. Armitage;K. Williams

Nuclear receptors as controlling factors in chemical metabolism: Determination of regulatory signal network crucial for co-ordinating cellular response to chemicals

核受体作为化学代谢的控制因素：调节信号网络的确定对于协调细胞对化学物质的反应至关重要