EAGER: Exploring Gene Network States

基因组研究表明，许多基因是普遍保守的，但过程很少。相比之下，基因网络和支配其状态的原则正在成为普遍性的可能焦点。为了解决这个问题，研究人员将利用两个单细胞生物体，它们的相对较低的复杂性应该会使识别基因活动的正式网络模式变得更加容易。研究人员将构建纤毛虫四毛草履虫和变形鞭毛虫Naegleria gruberi的菌株，这些菌株具有各种成对的基因敲除组合，然后使用这些菌株来测试这种操作对细胞行为和基因表达基因组模式的影响。通过他们的分析，PI将搜索可能代表细胞基本状态的共同网络模式。这种网络状态的保护很可能是进化中的一个关键因素，也可能是生命的基本要求。一个足以使这种网络组装、发挥功能并对新条件做出反应的谱系很可能是允许活细胞起源和存活的关键因素。因此，这项研究的成功还将对进化论和合成生物的可能性产生重大影响。新生命形式的成功合成反过来又有可能导致保护和改善环境健康的重大技术进步，以及对设计用于计算和通信的人工网络等应用的广泛影响。该项目的教育和培训方面将包括对博士后研究人员和本科生进行研究和基本科学问题的认真指导。公众宣传将包括关于基因和行为之间的关系以及基因网络的作用的讲座。

Genome studies have shown that many genes but few processes are universally conserved. In contrast, gene networks and the principles that govern their states are emerging as possible foci of universality. To address this issue, the investigator will exploit two unicellular organisms whose relatively low level of complexity should make discerning formal network patterns of gene activity much easier. The investigator will construct strains of the ciliate Paramecium tetraurelia and the amoebo-flagellate Naegleria gruberi having various pair-wise combinations of gene knockdowns, and then use these strains to test the effects of such manipulations on the cells' behaviors and on genomic patterns of gene expression. Through their analysis, the PI will search for common network patterns that may represent a cell's repertoire of fundamental states. Conservation of such network states is likely to be a critical factor in evolution and may be the fundamental requirement for life. A repertoire adequate for such networks to assemble, function, and respond to novel conditions may well be the key factor that permitted the origin and survival of living cells. As such, success in this study would also have major implications for evolutionary theory and for the plausibility of synthesizing living things. The successful synthesis of new life forms, in turn, has the potential to lead to major technological advances to protect and improve the health of the environment, as well as wide-ranging implications for applications such as designing artificial networks for computing and communications. Educational and training aspects of the project will consist of careful mentoring of postdoctoral researchers and undergraduate students in both the conduct of research and the underlying scientific questions. Public outreach will consist of lectures on the relationship between genes and behavior and the role of gene networks.