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Revision as of 11:47, 19 September 2005
- 3rd year graduate student in Pam Silver's lab.
- Biological and Biomedical Sciences graduate program
- Systems Biology department at the Harvard Medical School
- S.B. degrees in Mathematics and Biology from MIT, 2003.
Engineering a yeast cell-cycle counter
With the help of Caroline and Dirk, I am building a synthetic biological device that is designed to count mitotic divisions in the yeast Saccharomyces cerevisiae. This counter is designed to use cell-cycle regulated nuclear entry, mother-daughter and cell-cycle regulated differential transcription, and regulated proteolysis to generate a programmed transcriptional cascade that progresses with the cell cycle. Artificial zinc-finger transcription factors with both localization and degradation signal sequences have been engineered to perform these tasks. Ultimately, this cascade results in expression of fluorescent reporter proteins that indicate the age of the cell.
Once constructed, the counter will be a useful tool for the study of aging and other age-specific phenomena. Fluorescence-based sorting of age-specific populations and screens to identify lifespan-extending yeast mutants may be possible. In addition to the practical application of this technology, another focus of this project is to explore the design principles that govern the engineering of genetic circuits in eukaryotic cells. Currently, most synthetic devices have been built in prokaryotes. The construction of this cell-cycle counter investigates additional engineering possibilities that eukaryotes provide, such as cellular compartmentalization and regulated translocation. Knowledge of these principles will facilitate future design of more complex devices.