Functional and biochemical analysis of oligomeric intermediates of yeast prions formed in vivo

体内形成的酵母朊病毒寡聚中间体的功能和生化分析

• 批准号: BB/D018242/1
• 负责人: Mick Tuite
• 金额: $ 39.94万
• 依托单位: University of Kent
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD018242%2F1
• 关键词: Functional; biochemical; analysis; oligomeric; intermediates

For over a century there has been a near universal acceptance of Mendel's Laws of Inheritance to explain the faithful transmission of genetic information from one generation to the next. A nucleic acid-based hereditary unit, the gene, carries this information and the characteristics of an organism are defined by its set of genes. Over the last century a number of exceptions to Mendel's Laws have been identified, but a new challenge to the dogma that all inheritance is nucleic acid based has recently arisen from the discovery of prions. Although prions have been intensively studied as the disease-causing agents associated with 'Mad Cow Disease' and the human equivalent, Creutzfeldt-Jakob Disease (CJD), there is now a considerable body of scientific evidence that prions might actually represent an entirely new form of heredity, based on a protein molecule rather than a nucleic acid. This evidence comes from the analysis of novel prion-based 'genetic' determinants in Baker's Yeast (Saccharomyces cerevisiae) one of which (the so-called [PSI+] element) is being studied in this project. Our aim is to fully understand how such a protein-based determinant is generated de novo and then replicated aand passed on to other yeast cells when they grow and divide. We know that this requires cells to produce prion seeds which can be passed on to other cells and it is our objective to define the molecular composition of these seeds. Uisng advanced genetic and biochemical methods we will study different yeast prions and look in particular at the type of physical changes they go through in taking up their prion form. One outcome of this research might be identifying steps in the prion cycle that can be targetted by new drugs to block the formation of prion seeds.

一个多世纪以来，孟德尔遗传定律几乎被普遍接受，以解释遗传信息如何从一代人忠实地传递到下一代。基于核酸的遗传单位（基因）携带此信息，生物体的特征由其基因组定义。在上个世纪，孟德尔定律的一些例外情况已经被确定，但最近朊病毒的发现对“所有遗传都是基于核酸”这一教条提出了新的挑战。尽管朊病毒作为与“疯牛病”和人类类似的克雅氏病（CJD）相关的致病因子而得到了深入研究，但现在有大量科学证据表明，朊病毒实际上可能代表一种全新的遗传形式，其基于蛋白质分子而不是核酸。这一证据来自于对面包酵母（酿酒酵母）中新型基于朊病毒的“遗传”决定因素的分析，本项目正在研究其中之一（所谓的[PSI+]元素）。我们的目标是充分了解这种基于蛋白质的决定簇是如何从头产生的，然后在生长和分裂时复制并传递给其他酵母细胞。我们知道这需要细胞产生可以传递给其他细胞的朊病毒种子，我们的目标是定义这些种子的分子组成。利用先进的遗传和生化方法，我们将研究不同的酵母朊病毒，并特别研究它们在形成朊病毒形式时所经历的物理变化类型。这项研究的一个成果可能是确定朊病毒循环中的步骤，新药物可以针对这些步骤来阻止朊病毒种子的形成。

项目成果

Protection and matchmaking: the role of the molecular chaperone

保护与牵线搭桥：分子伴侣的作用

• 发表时间: 2008
• 期刊: The Biochemist
• 作者: Tuite MF

Yeast Gene Analysis - Second Edition

酵母基因分析 - 第二版

• DOI: 10.1016/s0580-9517(06)36020-5
• 发表时间: 2007
• 作者: Tuite M

Cellular factors important for the de novo formation of yeast prions.

对于酵母朊病毒的从头形成很重要的细胞因子。

• DOI: 10.1042/bst0361083
• 发表时间: 2008
• 期刊: Biochemical Society transactions
• 影响因子: 3.9
• 作者: Tuite M