After a PhD in Particle Physics (1999), I decided that deriving analytically quark confinement from the quantum chromodynamics field equations was important but too difficult. Therefore, the day after my dissertation I started a postdoc in biology, working on the computational design of proteins, using molecular modelling techniques (postdocs at ULB, with Prof. Wodak, ULP and Harvard U., with Prof. Karplus, Chemistry Nobel 2013).
After 4 years of postdocs in computational biology, I started as Assistant Professor to the Ecole Polytechnique (France), where I moved from atom-based automated design to systems-based computational design, developing novel methodologies to automatically design metabolic networks, transcriptional networks, and particularly RNA networks. In 2005, just after getting tenured, I discovered about iGEM and Synthetic Biology and I decided to move to experimental molecular biology. Unfortunately, this was not possible at the Ecole Polytechnique and Genopole (France) offered my a full microbiology wetlab in 2007 and I moved there in 2008 (as a sabbatical) but later I obtained a tenured position as CNRS Senior Researcher (2009). Starting an experimental lab was a greater leap than moving from Physics to Biology. This allowed me to combine computational design with experimental validation, which I could only do before through collaborations. In particular, I could validate my RNA circuits (which are easier and cheaper to build than the other networks I had been designing). There, I also developed and used automated microscopy and microfluidics chips for single-cell validations. In 2013, after knowing about the strong interest in Warwick about Synthetic Biology, I accepted a full Professor offer at the University of Warwick. The new exciting environment encouraged me to transmute my automated design methodology from using a computer to optimize to use phages and bacteria. Now, we also develop custom bioreactors using 3D printing.
About the lab
Our lab at the University of Warwick (http://synth-bio.org) currently hosts 3 PhD students, 3 scientists, 3 postdocs, a project administrator and several rotation students. The lab members come from all over the world (UK, France, Spain, Italy, Poland, Greece, India, China, …), but they also have very different study backgrounds (mechanical engineering, mathematics physics, biochemistry, biotechnology, molecular biology, and biomedicine). Our lab members are motivation driven and activities are developed to encourage innovative solutions. We believe that biological engineering will only succeed by embracing automation at all levels. Regulation using protein and/or RNA molecules is the circuitry of cells and an RNA-based regulation is the easiest to automate its design. We have recently extended our automated RNA design methodology to incorporate functional modules involving ribozymes and transcription terminators, which were characterised in E. coli (at the single-cell level using microfluidics and automated time-lapse microscopy) RNA sensors relying on conditional Hammer-Head Ribozymes.
About the project
Project 7: We have recently developed the first methodology to automatically design RNA circuits (Rodrigo et al. PNAS 2012). We experimentally validated with a sirboregulator system, but we have recently expanded it to the incorporation of RNA-only cascades, RNA heterodimers, RNA-based two-component signal transduction and RNA-based transistors, among others. For this work, we will use a number of different techniques, such as phage-assisted directed evolution, computational design, microscopy, microfluidics, and many more. We aim to design RNA-based sensors by computational design and directed evolution, which will be characterised in living cells at the single-cell and population levels.