Molecular Computation in Ciliates

纤毛虫的分子计算

• 批准号: 0622112
• 负责人: Laura Landweber
• 金额: --
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0622112&HistoricalAwards=false
• 关键词: Molecular; Computation; Ciliates

This research focuses on the interplay between molecular biology, computer science, and evolution to probe a complex form of biological information processing: geneunscrambling in ciliated protozoa. A long-term goal is to develop a multidisciplinaryapproach to this problem that will enable us to tap into this biological process as acomputational tool.Intellectual meritThe intellectual merit of the proposed activity is the unique combination of threeapproaches experiments, computational biology, and modeling to improve ourunderstanding of the function, mechanism, and logic of this phenomenon. Becausegene unscrambling in stichotrichous ciliates has the ability to assemble thousands ofgenes from tens of thousands of scrambled segments within a single genome, it isour opinion that DNA unscrambling in ciliates remains the most complex andspectacular, yet least explored, type of DNA computation known in biology. Thisproposal uses gene unscrambling as a model system to explore the mechanismsunderlying complex gene and genome rearrangements, the steps through whichthese processes have evolved, and their capacity to solve hard computationalproblems in vivo.Broader impactsThe broader impacts resulting from the prior NSF ITR award has been an influx ofnew ideas and direction from computational sciences into the study of a complexbiological system of programmed DNA rearrangements in ciliated protozoa andtraining of a varied, interdisciplinary group of students. The broader impacts resultingfrom the proposed activity would be expansion of the current work andinterdisciplinary student training, with even more synergy between different membersof the group from the computational and experimental sides, with the ultimate goal ofharnessing this process for the purpose of performing in vivo computation. Thestrength of the combined approach is its ability to recognize underlying quantitativeprinciples, which would otherwise be missed in descriptive studies of geneunscrambling alone, and the continued building and refinement of a strongquantitative framework to understand this natural computing paradigm. This isespecially germane as we enter the stage of post genomic data for ciliates,heightening the need for rigorous quantitative tools and analysis to understand hownature implements complex data structures in molecular biology. These studies of'BioWare' offer a glimpse into one of nature's attempts to explore the diverse rangeand capacity of modern genetic systems.

这项研究集中在分子生物学、计算机科学和进化之间的相互作用，以探索一种复杂的生物信息处理形式：纤毛原生动物的基因解读。一个长期的目标是开发一种多学科的方法来解决这个问题，使我们能够将这个生物过程作为计算工具来挖掘。智力上的优点拟议的活动的智力上的优点是三种方法的独特结合，即实验、计算生物学和建模，以提高我们对这一现象的功能、机制和逻辑的理解。由于在纤毛虫中破解DNA具有从数万个杂乱片段中组装数千个基因的能力，因此我们认为，在纤毛虫中破译DNA仍然是生物学中已知的最复杂、最壮观但探索最少的DNA计算类型。这项建议使用基因解读作为一个模型系统来探索复杂的基因和基因组重排的潜在机制，这些过程已经进化的步骤，以及它们解决活着的困难计算问题的能力。更广泛的影响来自先前的NSF ITR奖所产生的更广泛的影响是，来自计算科学的新思想和方向涌入到对纤毛原生动物编程DNA重排的复杂生物学系统的研究中，并培训了一批不同的、跨学科的学生。拟议活动产生的更广泛影响将是扩大目前的工作和跨学科的学生培训，在计算和实验方面小组不同成员之间甚至有更多的协同作用，最终目标是利用这一过程进行活体计算。这种组合方法的优势在于它能够识别潜在的量化原则，否则仅在基因解读的描述性研究中就会遗漏这些原则，并继续建立和完善一个强大的量化框架来理解这一自然计算范式。随着我们进入纤毛虫的后基因组数据阶段，这一点尤其密切相关，这增加了对严格的定量工具和分析的需求，以了解自然如何在分子生物学中实现复杂的数据结构。这些对‘BioWare’的研究让我们得以一窥自然界探索现代遗传系统多样性范围和能力的尝试之一。