BFS GOTChAs, April 2010

This page contains some GOTChA charts for possible rotation projects in the lab this summer.

Device Projects

The following GOTChAs are for projects that involve building new device technologies that can be used to push biological circuit design forward.

Integrated Load and Context Compensation

Goals Design a transcriptional regulator that uses feedback to compensate for changes in load and changes in context and thus provides consistent performance independent of downstream loading or cellular context (cell strain, growth media) Example: A -| B, designed so that transfer curve is maintained across changes in downstream reactions involving B, cell strain, growth media

Technical Challenges

Objectives Characterize the performance of existing transcriptional regulators across 3 cell strains, 3 growth media and 3 loading conditions. Design a compensation circuit that measures output level and regulates device performance to compensate for uncertainty Idea: use RNA-based feedback in 5' UTR sequences to measure transcription and compensate Note: feedback dynamics should be 5-10X regulatory dynamics to allow for use in non-equilibrium circuits Measure the performance of one or more compensation circuits and compare to existing regulators Regulation circuitry should be "internal" to device, so that inputs and outputs are the same as traditional regulator

Approach

Fast Mechanisms for Biomolecular Feedback

Goals Design a set of devices for implementing feedback circuits that have timescales measured in seconds instead of minutes

Technical Challenges

Objectives Identify the mechanisms and timescales of various feedback mechanisms in natural systems Example: feedback mechanisms involved in chemotaxis Use models to estimate the bandwidth of regulators based on transcriptional feedback, post-transcriptional feedback, translational feedback, post-translational feedback, and covalent modifications Formulate a test setup that can be used to characterize the speed of response of one or more circuits using different mechanisms Implement a fast-feedback mechanism using one of the following methods: RNA-based feedback using anti-sense interference RNA-based feedback using secondary structure Programmable scaffolds for phosphorylation cascades Measure the response speed of one or more regulation mechanisms and demonstrate seconds-timescale response

Approach

Robustness Projects

CAGEN

Objectives

Goals	Technical Challenges
Approach