DTI: 2010–11 Funded Proposals

Yiannis Kaznessis, Marc Riedel, Claudia Schmidt-Dannert

Computational Methods for Forward Biological Engineering

Synthetic biology is a flourishing discipline that shares principles, tools, and objectives with biological and engineering sciences. The goal of synthetic biology is the construction of new DNA or RNA sequences that give rise to new biological behaviors. These behaviors mimic the dynamics of simple electronic circuits/devices like logical AND gates, switches, oscillators and feedback loops.

Mathematical modeling is an important component of scientific and engineering disciplines. It can play an important role in synthetic biology the same way modeling helps in VLSI, aircraft or architecture design: models can provide a clear picture of how different components influence the behavior of the whole, reaching objectives quickly.

The proposed work focuses on the development and dissemination of mathematical methods and modeling tools for computer aided design of synthetic gene regulatory networks. The proposed mathematical models will connect synthetic DNA sequences to complex biological dynamics and facilitate forward engineering of gene networks. With the proposed computational tools, users will generate testable hypothesis, design, perturb and optimize the sequence of synthetic DNA constructs, test predictions and rationally engineer a targeted dynamic behavior in living bacterial organisms.

Our objective is the following: Develop and disseminate software tools for synthetic biology applications. We propose to create a computational platform with the following components: 1) a database of standard synthetic biological components; 2) user friendly interfaces to flexibly access, retrieve and manipulate the database information; 3) a tool that automatically generates models of these synthetic constructs; 4) a repository of these models; 5) tools to modify and improve the models; 6) a simulation engine to conduct computer simulations of these constructs.