Design of Cross- and Multi-species Genetic Circuits

Bioengineering of genetic and metabolic circuits has a wide range of applications. However, most efforts in circuit design are currently limited to a small subset of laboratory model organisms used in monocultures, many of which may be incompatible for their target applications. Expanding circuit design to a novel organism remains an uphill task that requires characterisation of new genetic parts and re-construction of the circuit for each new organism of interest. This doctoral project aims to develop tools and strategies for building cross-species compatible genetic circuits. We expect the results of the work to facilitate rapid implementation of circuits in non-model organisms, while preserving their function, and enabling their deployment in multi-species communities. The tools developed here will help expedite the design and implementation of synthetic genetic and metabolic circuits in new chassis organisms suited for diverse biotechnology applications.

**Teams' presentation**

The Cellular Computing team aims to engineer synthetic genetic circuits with increasing levels of complexity: going from the molecular-level in cell-free systems to the multicellular level in co-cultures, with intercellular exchange. By integrating experimental data with mathematical modelling, we strive to understand and predict the behaviour of these circuits, facilitating optimisation and scaling up. Finally, we will use the knowledge generated to improve computer-aided design and automate the process of designing new genetic circuits with diverse functionalities, and across diverse organisms. Our long-term vision is to advance the field of synthetic biology and pave the way for transformative applications in bioengineering and biotechnology.

Cosynus team is dedicated to creating innovative strategies for bioproduction from microbial cell factories by utilizing renewable carbon sources as a sustainable alternative to petrochemical sources. We are actively working on implementing synthetic biology tools and strategies to transform our chassis strain, the yeast Yarrowia lipolytica, into an industrial cell factory producing value-added molecules like pigments and terpenes. To improve productivity and to alleviate bottleneck like metabolic burden arose from massive genetic engineering, we are setting up synthetic consortia with « division of labor » strategy. Our emphasis is on developing methodologies to establish community systems and understanding metabolic interaction within synthetic consortia.

**Micalis presentation**

The Micalis Institute is a joint research unit between INRAE, AgroParisTech, and the University of Paris-Saclay. At Micalis, our focus is on pioneering and impactful research related to microorganisms that influence food, gut microbiota, and sustainable food production, all pivotal to human health. The microorganisms we study are integral  to:

>Food Microbiomes: These are crucial for the fermentation and preservation of food, and they play a role in the transmission of foodborne pathogens.

>Digestive Microbiomes: These operate in symbiosis with the host and are linked to the emergence of various human pathologies when disrupted.

>Model Microorganisms: Bacteria and yeasts that facilitate fundamental research and the engineering of metabolic pathways and cellular factories for producing valuable molecules.

**INRAE presentation**

The French National Research Institute for Agriculture, Food, and Environment (INRAE) is a major player in research and innovation. It is a community of 12,000 people with 272 research, experimental research, and support units located in 18 regional centres throughout France. Internationally, INRAE is among the top research organisations in the agricultural and food sciences, plant and animal sciences, as well as in ecology and environmental science. It is the world’s leading research organisation specialising in agriculture, food and the environment. INRAE’s goal is to be a key player in the transitions necessary to address major global challenges. Faced with a growing world population, climate change, resource scarcity, and declining biodiversity, the Institute has a major role to play in building solutions and supporting the necessary acceleration of agricultural, food and environmental transitions.

We are looking for a highly motivated candidate with experience in experimental synthetic biology, including microbiology and molecular biology techniques. Although not essential, some background in programming, bioinformatics, or computational modelling would be an added advantage. They should have strong communication skills and the willingness to work collaboratively with other members of the team and project collaborators, including biologists, engineers, mathematicians, and computer scientists. A Master’s degree or equivalent is required for PhD registration at the Structure et dynamique des systèmes vivants (SDSV) doctoral school of the University of Paris-Saclay.