Section: Partnerships and Cooperations

International Initiatives

• Title: Artificial tissue homeostasis: combining synthetic and computational biology approaches

• Inria principal investigator: Grégory Batt

• International Partner (Institution - Laboratory - Researcher):

  • Massachusetts Institute of Technology (United States) - Weiss Lab

• Duration: 2012 - 2014

Cell-based gene therapy aims at creating and transplanting genetically-modified cells into a patient in order to treat an illness. Ideally, actively-growing cells are used to form a self-maintaining tissue in the patient, thus permanently curing the disease. Still, before any real therapeutic use, many important issues need to be addressed. In particular, one should guarantee tissue homeostasis, that is, that the size of the newly-introduced tissue remains within admissible bounds. The TISHOM project focused on developing methods and tools to facilitate the design and effective construction of artificial tissues.

In the context of his PhD, Xavier Duportet worked on three projects on engineering human cells. The first one, dealing with developing tools to facilitate the engineering of mammalian cells, has been published [7] . The two others deal with the development of communication systems and still need to be finalized. This experimental work raised a number of more theoretical questions, that were investigated by François Bertaux, together with Szymon Stoma. Two problems have been investigated. The first one dealt with accounting for protein fluctuations for the analysis of signal transduction systems over long time scales and has been published [4] . The second one dealt with the multiscale simulation of tissues and is still under way. During the course of the project, a third line of research emerged, to assist the design of a patterning system currently developed by the Weiss lab. On the computational side, the major issues have been addressed. On the experimental side, additional constructions and characterizations are still needed.

Lastly, the associated team also helped to organize the workshop Design, optimization and control in systems and synthetic biology . Nearly 200 researchers and students attended this event. Although of relatively modest size, this event was attended by a number of leaders of the field and had a significant international visibility.

Since 2012, we have a collaboration with Prof. Jie-Hong Jiang, National Taiwan University first on hybrid simulations of biochemical reaction systems and now on the design of a compiler of digital programs and analog circuits in biochemical reactions. Our preliminary results and common publications on this topic [15] , [16] are encouraging but a lot of work is needed to minimize the number of necessary species and reactions. Our aim, in partnership with Franck Molina (CNRS, Sysdiag, Montpellier) is to design a biosensor using our biochemical programming compiler, implement the generated code in a liposome using a microfluidic device, and test its efficacy in vitro.