This research focuses on the interplay between molecular biology, computer science, and evolution to probe a complex form of biological information processing: gene unscrambling in ciliated protozoa. A long-term goal is to develop a multidisciplinary approach to this problem that will enable us to tap into this biological process as a computational tool.

Intellectual merit The intellectual merit of the proposed activity is the unique combination of three approaches experiments, computational biology, and modeling to improve our understanding of the function, mechanism, and logic of this phenomenon. Because gene unscrambling in stichotrichous ciliates has the ability to assemble thousands of genes from tens of thousands of scrambled segments within a single genome, it is our opinion that DNA unscrambling in ciliates remains the most complex and spectacular, yet least explored, type of DNA computation known in biology. This proposal uses gene unscrambling as a model system to explore the mechanisms underlying complex gene and genome rearrangements, the steps through which these processes have evolved, and their capacity to solve hard computational problems in vivo.

Broader impacts The broader impacts resulting from the prior NSF ITR award has been an influx of new ideas and direction from computational sciences into the study of a complex biological system of programmed DNA rearrangements in ciliated protozoa and training of a varied, interdisciplinary group of students. The broader impacts resulting from the proposed activity would be expansion of the current work and interdisciplinary student training, with even more synergy between different members of the group from the computational and experimental sides, with the ultimate goal of harnessing this process for the purpose of performing in vivo computation. The strength of the combined approach is its ability to recognize underlying quantitative principles, which would otherwise be missed in descriptive studies of gene unscrambling alone, and the continued building and refinement of a strong quantitative framework to understand this natural computing paradigm. This is especially germane as we enter the stage of post genomic data for ciliates, heightening the need for rigorous quantitative tools and analysis to understand how nature implements complex data structures in molecular biology. These studies of 'BioWare' offer a glimpse into one of nature's attempts to explore the diverse range and capacity of modern genetic systems.

Project Start
Project End
Budget Start
2006-09-01
Budget End
2010-08-31
Support Year
Fiscal Year
2006
Total Cost
$918,000
Indirect Cost
Name
Princeton University
Department
Type
DUNS #
City
Princeton
State
NJ
Country
United States
Zip Code
08540