Protein Complexes and Human Genetic Disease

蛋白质复合物与人类遗传疾病

基本信息

  • 批准号:
    MR/M02122X/1
  • 负责人:
  • 金额:
    $ 117.6万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Fellowship
  • 财政年份:
    2015
  • 资助国家:
    英国
  • 起止时间:
    2015 至 无数据
  • 项目状态:
    已结题

项目摘要

Many human diseases are caused by genetics -- that is, the genes that you inherited from your parents. Slight variations between the genes of different people can have wide-ranging effects. Understanding how this genetic variation contributes to disease is of huge importance for disease prevention, diagnosis and treatment. While much progress has been made in recent years, aided by the ability to sequence genes and genomes at much lower cost, there is still much we do not understand about how differences between genes can cause disease.Most genes can be thought of quite simply as a set of instructions on how to build a protein. These are called "protein-coding" genes. Genetic changes in protein-coding genes can modify these instructions, thus affecting the protein, either by changing its structure, or by causing more or less to be made. Therefore, one thing that has been quite useful for understanding genetic disease is to consider how proteins will be affected. Genetic variations that cause large changes to proteins are much more likely to cause disease.One aspect of this that has been often ignored is the fact that most proteins do not exist in isolation. Instead, many proteins can bind to other proteins and form "protein complexes". Such protein complexes are fundamental to nearly all biological processes. A major focus of my past research was on trying to understand how proteins assemble into complexes. In the current research proposal, I aim to build upon this, and to study how protein complexes are related to human genetic disease. Specifically, I believe that a genetic change is more likely to cause a disease if it affects a protein that assembles into a complex, and that this will depend upon the type of complex that is formed. In fact, early results I present in this proposal strongly suggest this to be true.The ultimate aim of this research will be to develop improved methods for predicting whether genetic changes are likely to cause disease. Such methods exist now, but they don't use information on protein complexes. By incorporating the knowledge of protein complexes that will be obtained from this project, we should be able to substantially improve upon existing predictions.The benefits of improved predictions are great. In particular, they will significantly enhance our ability to identify specific genetic changes that cause diseases or affect other human traits. Furthermore, they could be used in a clinical setting, to predict from a person's genes whether they are likely to get a specific disease, or to diagnose whether their symptoms could be caused by a genetic disorder.
许多人类疾病是由基因引起的,也就是说,你从父母那里遗传的基因。不同人基因之间的微小差异可能会产生广泛的影响。了解这种基因变异是如何导致疾病的,对疾病的预防、诊断和治疗具有重要意义。近年来,由于能够以更低的成本对基因和基因组进行测序,研究取得了很大进展,但对于基因之间的差异如何导致疾病,我们仍有很多不了解的地方。大多数基因都可以被简单地理解为一组关于如何构建蛋白质的指令。这些被称为“蛋白质编码”基因。蛋白质编码基因的遗传变化可以改变这些指令,从而通过改变其结构或导致产生或多或少的蛋白质来影响蛋白质。因此,对理解遗传疾病非常有用的一件事是考虑蛋白质将如何受到影响。导致蛋白质发生巨大变化的基因变异更有可能导致疾病。其中一个经常被忽视的方面是,大多数蛋白质并不是孤立存在的。相反,许多蛋白质可以与其他蛋白质结合,形成“蛋白质复合物”。这些蛋白质复合物是几乎所有生物过程的基础。我过去研究的一个主要焦点是试图理解蛋白质如何组装成复合物。在目前的研究计划中,我的目标是以此为基础,研究蛋白质复合物如何与人类遗传疾病相关。具体地说,我相信如果基因变化影响到一种组装成复合体的蛋白质,那么它更有可能导致疾病,而这取决于形成的复合体的类型。事实上,我在这个提议中提出的早期结果有力地表明这是正确的。这项研究的最终目的将是开发改进的方法来预测遗传变化是否可能导致疾病。这种方法现在已经存在,但它们不使用蛋白质复合物的信息。通过结合从这个项目中获得的蛋白质复合物的知识,我们应该能够大大改进现有的预测。改进预测的好处是巨大的。特别是,它们将显著提高我们识别导致疾病或影响其他人类特征的特定基因变化的能力。此外,它们还可以用于临床环境,从一个人的基因中预测他们是否可能患上某种特定疾病,或者诊断他们的症状是否可能由遗传疾病引起。

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)
Ligand Binding Site Structure Influences the Evolution of Protein Complex Function and Topology.
  • DOI:
    10.1016/j.celrep.2018.02.085
  • 发表时间:
    2018-03-20
  • 期刊:
  • 影响因子:
    8.8
  • 作者:
    Abrusán G;Marsh JA
  • 通讯作者:
    Marsh JA
Alpha Helices Are More Robust to Mutations than Beta Strands.
  • DOI:
    10.1371/journal.pcbi.1005242
  • 发表时间:
    2016-12
  • 期刊:
  • 影响因子:
    4.3
  • 作者:
    Abrusán G;Marsh JA
  • 通讯作者:
    Marsh JA
Understanding molecular mechanisms and predicting phenotypic effects of pathogenic tubulin mutations
  • DOI:
    10.1101/2022.06.16.496400
  • 发表时间:
    2022-06
  • 期刊:
  • 影响因子:
    4.3
  • 作者:
    T. Attard;J. Welburn;J. Marsh
  • 通讯作者:
    T. Attard;J. Welburn;J. Marsh
Understanding molecular mechanisms and predicting phenotypic effects of pathogenic tubulin mutations.
  • DOI:
    10.1371/journal.pcbi.1010611
  • 发表时间:
    2022-10
  • 期刊:
  • 影响因子:
    4.3
  • 作者:
  • 通讯作者:
Ligand-Binding-Site Structure Shapes Allosteric Signal Transduction and the Evolution of Allostery in Protein Complexes
  • DOI:
    10.1093/molbev/msz093
  • 发表时间:
    2019-08-01
  • 期刊:
  • 影响因子:
    10.7
  • 作者:
    Abrusan, Gyorgy;Marsh, Joseph A.
  • 通讯作者:
    Marsh, Joseph A.
{{ 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 }}

Joe Marsh其他文献

Joe Marsh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('Joe Marsh', 18)}}的其他基金

Protein Variant Interpretation
蛋白质变异解释
  • 批准号:
    MC_UU_00035/9
  • 财政年份:
    2023
  • 资助金额:
    $ 117.6万
  • 项目类别:
    Intramural

相似国自然基金

新型IIIB、IVB 族元素手性CGC金属有机化合物(Constrained-Geometry Complexes)的合成及反应性研究
  • 批准号:
    20602003
  • 批准年份:
    2006
  • 资助金额:
    26.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

Molecular mechanisms underlying the assembly of the human proteasome and endogenous protein complexes
人类蛋白酶体和内源蛋白复合物组装的分子机制
  • 批准号:
    10670424
  • 财政年份:
    2022
  • 资助金额:
    $ 117.6万
  • 项目类别:
Molecular mechanisms underlying the assembly of the human proteasome and endogenous protein complexes
人类蛋白酶体和内源蛋白复合物组装的分子机制
  • 批准号:
    10500937
  • 财政年份:
    2022
  • 资助金额:
    $ 117.6万
  • 项目类别:
Exploring functional complexes and disease networks within human RNA-binding protein interactomes
探索人类 RNA 结合蛋白相互作用组中的功能复合物和疾病网络
  • 批准号:
    10200550
  • 财政年份:
    2020
  • 资助金额:
    $ 117.6万
  • 项目类别:
Exploring functional complexes and disease networks within human RNA-binding protein interactomes
探索人类 RNA 结合蛋白相互作用组中的功能复合物和疾病网络
  • 批准号:
    9806758
  • 财政年份:
    2019
  • 资助金额:
    $ 117.6万
  • 项目类别:
Exploring functional complexes and disease networks within human RNA-binding protein interactomes
探索人类 RNA 结合蛋白相互作用组中的功能复合物和疾病网络
  • 批准号:
    10650886
  • 财政年份:
    2019
  • 资助金额:
    $ 117.6万
  • 项目类别:
Exploring functional complexes and disease networks within human RNA-binding protein interactomes
探索人类 RNA 结合蛋白相互作用组中的功能复合物和疾病网络
  • 批准号:
    10624675
  • 财政年份:
    2019
  • 资助金额:
    $ 117.6万
  • 项目类别:
The molecular mechanisms of human phosphatidylinositol 4 kinase IIIß regulation by host and viral protein complexes
宿主和病毒蛋白复合物调节人磷脂酰肌醇 4 激酶 III 的分子机制
  • 批准号:
    504185-2017
  • 财政年份:
    2019
  • 资助金额:
    $ 117.6万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
The molecular mechanisms of human phosphatidylinositol 4 kinase IIIß regulation by host and viral protein complexes
宿主和病毒蛋白复合物调节人磷脂酰肌醇 4 激酶 III 的分子机制
  • 批准号:
    504185-2017
  • 财政年份:
    2018
  • 资助金额:
    $ 117.6万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
The molecular mechanisms of human phosphatidylinositol 4 kinase IIIß regulation by host and viral protein complexes
宿主和病毒蛋白复合物调节人磷脂酰肌醇 4 激酶 III 的分子机制
  • 批准号:
    504185-2017
  • 财政年份:
    2017
  • 资助金额:
    $ 117.6万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Deciphering the Molecular Underpinnings of Human Neuronal Protein Complexes In Autism Spectrum Disorder
破译自闭症谱系障碍中人类神经元蛋白复合物的分子基础
  • 批准号:
    367376
  • 财政年份:
    2016
  • 资助金额:
    $ 117.6万
  • 项目类别:
    Studentship Programs
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了