Molecular Computation in Ciliates

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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.