PhD Case Award in collaboration with Microsoft Research: Synthesizing Programmable Biological Circuits Using DNA, RNA, and Enzymes

Supervisor: Dr Vishwesh Kulkarni
Start date: As soon as possible.

Duration: 4 years

Are you keen to undertake this work that builds on our prior collaboration with Microsoft Research that will facilitate a relevant toolbox for the Visual DSD software? In this project, we propose the first known results on how nucleic acids can be used to implement a wide range of polynomials, rational functions, and programmable Hill-type nonlinearities.

Project Overview:

The programmability of Watson-Crick base pairing, combined with a decrease in the cost of synthesis, has made the direct use of nucleic acids for performing computation a promising approach for the engineering of biological circuits. In cell-free settings, many results are now available on how to scale up system complexity and quantitatively characterize reaction mechanisms to an extent that is infeasible for engineered gene circuits or other cell-based technologies. However, most of the current results on programmable biomolecular circuits are limited to Boolean networks and it is not possible today to implement a wide range of polynomials, rational functions, and Hill-type nonlinearities in a programmable manner using nucleic acids. So, there is a clear need to develop the theory and software to synthesize programmable linear and nonlinear dynamic nucleic acid systems. Much as MATLAB is used in traditional engineering applications, this software will help in (1) simulating the behaviour of biological networks under a wide range of operating conditions and (2) synthesizing superior DNA-based biosensors and bioactuators. This project is focused on how nucleic acid based circuits and the associated software Visual DSD can be developed to implement these functions. Comprehensive information concerning this project and Visual DSD is available on http://research.microsoft.com/en-us/groups/biology/.

Experience of mathematical programming in C++ and MATLAB is required. The candidate should be proficient at implementing programmable circuits in wet-lab, either in vivo or in vitro. This project will require a hands-on approach and the expectation is that self-motivated candidates with excellent interpersonal skills and abilities will perform excellent research leading to high quality outcomes and publications.