Towards a Universal Biological-Cell Operating System (AUdACiOuS)

A living cell, e.g. a bacterium, is an information-processing machine. It is composed of a series of sub-systems that work in concert by sensing external stimuli, assessing its own internal states and making decisions through a network of complex and interlinked biological regulatory networks (BRN) motifs that act as the bacterium neural network. A bacterium's decision making processes often result in a variety of outputs, e.g. the creation of more cells, chemotaxis, bio-film formation, etc. It was recently shown that cells not only react to their environment but that they can even predict environmental changes. The emerging discipline of Synthetic Biology (SB), considers the cell to be a machine that can be built -from parts- in a manner similar to, e.g., electronic circuits, airplanes, etc. SB has sought to co-opt cells for nano-computation and nano-manufacturing purposes. During this leadership fellowship programme of research I will aim at making E.coli bacteria much more easily to program and hence harness for useful purposes. In order to achieve this, I plan to use the tools, methodologies and resources that computer science created for writing computer programs and find ways of making them useful in the microbiology laboratory.

This proposal will have impact in four main areas.

General Dissemination Pathway: as any interdisciplinary research project we will aim at publishing in the very top specialised (Computer Science, Synthetic Biology) and generalist journals (Nature, Science, PNAS). Our work will also be disseminated through the respective conferences and we have planed a series of workshop that will help up showcase our work and make it available to other academics and industrialist.

Wider Impact, Exploitation & Knowledge Transfer Pathway: The technology I will develop during my fellowship is an *enabling* technology. As such it will open the doors for cooperation across a range of disciplines. Notably, we propose to transfer knowledge back and forth across three main areas of research, namely, computer science, synthetic biology and -for the first time- DNA and RNA origami. This could very well seed new research lines and have impact on fields as varied as biomedical applications, the in vivo construction of detection sensors, and smard drug delivery systems.

Intellectual Property Protection and Technology Transfer: We will actively seek routes of commercial exploitation of our research and intellectual property will be protected as to guarantee a return to UK PLC.


Society At Large Related Pathway: The research ideas in this proposal are groundbreaking and could herald a revolution in the way synthetic biology projects are undertaken lowering the barrier to usability, complexity and ultimatly, impacting on practical applications. As such, this technology may also raise important ethical, social, legal issues that must be explored in conjunction with relevant stake holders (public, government, industry, academy, NGOs, regulators, etc). I have established a rigorous pathway to impact that embraces ELSI as well as science, technology and societal considerations.