Boston University

Cellicon Technologies, Inc.

Timothy S Gardner

James Joseph Collins

Boris Hayete

Jeremiah Faith

The invention relates to computer-implemented methods and systems for identifying regulatory relationships between expressed regulating polypeptides and targets of the regulatory activities of such regulating polypeptides. More specifically, the invention provides a new method for identifying regulatory dependencies between biochemical species in a cell. In particular embodiments, provided are computer-implemented methods for identifying a regulatory interaction between a transcription factor and a gene target of the transcription factor, or between a transcription factor and a set of gene targets of the transcription factor. Further provided are genome-scale methods for predicting regulatory interactions between a set of transcription factors and a corresponding set of transcriptional target substrates thereof.

Method to determine transcriptional regulation pathways in organisms

Provided are methods and compositions for regulating gene expression in a cell. The invention provides recombinant genetic toggle switches which contain a first constitutive promoter-regulatory gene operon and a second constitutive promoter-regulatory gene operon. Expression of the regulatory gene from the first operon inhibits expression from the promoter in the second operon, and expression of the regulatory gene from the second operon inhibits expression from the promoter in the first operon. By use of the toggle switch and various switching agents it is possible to reversibly switch the expression of a gene of interest between a stable 'on' state and stable 'off' state or vice versa via transient exposure to a switching agent.

Bistable genetic toggle switch

Provided are methods and compositions for regulating gene expression in a cell. The invention provides recombinant adjustable-threshold switches which contain a first inducible promoter-regulatory gene operon and a second constitutive promoter-regulatory gene operon. A threshold amount of activating agent is required to switch the inducible promoter &ldquo;on&rdquo; and the constitutive promoter &ldquo;off&rdquo;. An adjustable-threshold switch is useful to reversibly switch the expression of a gene of interest between a stable &ldquo;on&rdquo; state and stable &ldquo;off&rdquo; state in response to an activating agent at or above a threshold concentration.

Adjustable threshold switch

Provided are methods and compositions for regulating gene expression in a cell. The invention provides recombinant multi-state genetic oscillators containing an adjustable-threshold genetic switch that is periodically activated by an oscillating amount of an activator agent. The activating agent is a gene product expressed from a promoter regulated by the adjustable-threshold switch and thus forms a feedback loop that causes periodic switching of the adjustable-threshold switch between an &ldquo;on&rdquo; state and an &ldquo;off&rdquo; state. Multi-state genetic oscillators are useful to express one or more genes of interest in a periodic manner without requiring a periodic application of an external activating agent.

Growing community of inventors

Needham, MA, United States of America

Timothy S Gardner