Team:Penn/Project2

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Project

Abstract

The code of life is much more than a sequence of A's, G's, C's and T's; a suite of epigenetic mechanisms, ranging from chromatin remodeling to non-coding RNAs, affect gene expression and cellular function.

In particular, DNA methylation has been shown to alter transcriptional activity in a powerful, heritable manner. Abnormal methylation patterns are associated with diseases including immunodeficiency syndromes, neurodevelopmental disorders, and many types of cancer. Comprehensive understanding and control of DNA methylation could be invaluable to researchers studying these diseases.

Synthetic biologists and geneticists are accustomed to turning genes on and off at will, but the tools don’t exist to easily manipulate epigenetic patterns. We are developing a novel fusion protein that enables site-specific methylation, which can repress promoter activity with high precision.

In coming years, this fusion protein could become a powerful tool for epigenetics researchers looking to perform on/off studies in the vein of classical genetics, as well as an orthogonal mode of repressing constitutive promoters for bacterial synthetic biologists. Eventually, it could even give clinical researchers the means to restore healthy methylation levels in many insofar-untreatable epigenetic diseases.