Alfonso JaramilloView all speakers
Dr. Alfonso Jaramillo, Institute of Systems and Synthetic Biology (France), is a senior research scientist at CNRS and group leader of the Synth-Bio group. He held previously a tenured faculty position at Ecole Polytechnique (the top higher education college in France according to most rankings). He holds a PhD in Theoretical Physics (1999) and a Habilitation in molecular biology (2007).
He directs a microbiology lab (equipped with in house automated microscopy and microfabrication fab) that currently employs 10 researchers. He has published 61 papers and refereed conference proceedings, and he is currently member of several editorial boards. He has participated in 6 EU-funded consortia in Synthetic Biology and he has co-ordinated 2 of them.
The reprogramming of cells with novel behavior involves the engineering of synthetic circuits manipulating of DNA, RNA and/or proteins, which requires targeting nucleic acids with high specificity. RNA is an ideal molecule to be used as molecular interaction domains able to recognize other RNA or DNA. Unfortunately, RNA stability and function depends critically on global interactions, which often prevents a modular design strategy. This is particularly relevant when designing allosteric conformations in the RNA to create switching behavior. Such design could be done using computational methods. For this, we show how using standard secondary structure methods can already produce RNA switches working in E. coli if we incorporate evolutionary computation algorithms. There, we automatically optimize the sequences of a RNA circuit by minimizing their interaction activation and formation energies. Such objective function implements known RNA stability and kissing loop mechanisms. The recent engineering of self-assembly DNA interaction pathways in vitro by computational algorithms could not be extended to RNA in living cells until now. Here we report a general de novo RNA circuit design approach, where we have experimentally validated in E. coli fully synthetic RNAs displaying switching behavior. We also show in E. coli that our riboregulatory devices can be combined with known functional RNA fragments (such as ribozymes and aptamers) to create complex RNA circuits in bacteria. We also characterized their in vivo RNA dynamics by using microfluidics time-lapse microscopy to track single-cells. Our work provides a new paradigm to design functional RNAs circuits by only relying on RNA stability and RNA-RNA interactions.