Molecular Computation in Ciliates

本研究的重点是分子生物学，计算机科学和进化之间的相互作用，探索生物信息处理的复杂形式：纤毛虫原生动物的基因解读。一个长期的目标是开发一个多学科的方法来解决这个问题，这将使我们能够利用这个生物过程作为计算工具。智力价值所提出的活动的智力价值是三种方法的独特组合实验，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stichotrichous纤毛虫中的基因解读有能力将成千上万个基因从单个基因组中的成千上万个混乱片段中组装起来，因此我们认为纤毛虫中的DNA解读仍然是生物学中已知的最复杂和最壮观，但探索最少的DNA计算类型。该提案使用基因解读作为一个模型系统来探索复杂基因和基因组重排的机制，这些过程的进化步骤，更广泛的影响先前的NSF ITR奖产生的更广泛的影响是计算科学的新思想和方向涌入到程序DNA重排的复杂生物系统的研究中，纤毛虫原生动物和培训一个多样化的，跨学科的学生群体。拟议活动产生的更广泛的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，小组的不同成员之间产生更多的协同作用，最终目标是利用这一过程进行体内计算。综合方法的优势在于它能够识别潜在的定量原则，否则在单独的基因解读描述性研究中会错过这些原则，并继续建立和完善一个强大的定量框架来理解这种自然计算范式。当我们进入纤毛虫后基因组数据阶段时，这一点尤其重要，这就增加了对严格的定量工具和分析的需求，以了解自然界如何在分子生物学中实现复杂的数据结构。这些对“生物制品”的研究让我们得以一窥自然界探索现代遗传系统多样性和能力的尝试之一。

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.