SIGSYNCELL, a European project for synthetic cells

What are synthetic cells?
Jean-Christophe Baret1  – Researchers are trying to reproduce or invent small-scale systems that resemble biological systems. A synthetic cell, which measures between 1-100 microns, consists of microcompartments that enable it to fulfil the basic functions of life, such as chemical synthesis, molecule import-export, and the management of energy inputs. Researchers are focused on reproducing the full range of these functions.

The primary applications for synthetic cells are of interest to the biomedical and materials synthesis sectors, notably for the production of molecules based on biomimetic processes. But as far as we are concerned, SIGSYNCELL2  largely remains a basic research project. We emphasize a bottom-up approach that sets out from the fundamental building blocks, which we then assemble in order to obtain the desired functions. This involves engineering life from synthetic building blocks.

How would you present SIGSYNCELL and its objectives?
J.-C. B. : SIGSYNCELL is a consortium that brings together a dozen European academic partners3 , in addition to private companies4 . We are interested in a specific subsection of the problems arising from building synthetic cells, namely communication. In living beings, different compartments communicate among themselves, while cells interact with both similar cells and the external environment. These processes must be successfully reproduced in order to effectively generate synthetic cells.

Part of the broader European synthetic cells consortium SynCellEU, SIGSYNCELL will last four years. This is far too short to develop applications, but we will improve our basic understanding of issues relating to communication and interaction. To do so, we will use technologies and principles that do not necessarily have an equivalent in nature. We use all physicochemical processes at our disposal, especially the manipulation of artificial cells using light, as well as electric and magnetic fields.

In living beings, communication primarily occurs via chemical messages. These exchanges of molecules between cellular compartments and between cells are more or less guided; we specifically want to imitate this transport, but with more controlled procedures. This raises numerous questions relating to signalisation, on the best way to send a molecule from one compartment to another, while ensuring it does not go elsewhere.

We also have to work on cell membranes, so that they have receptors that can transmit information. This requires controlling the chemistry of the membrane in order for it to let the signal pass through at the selected moment. We also want to trigger changes within a cell when a specific molecule is detected outside

• 1Jean-Christophe Baret is a professor at Université de Bordeaux, as well as a member of the Centre de recherche Paul Pascal (CRPP, CNRS/Université de Bordeaux). He is a specialist in microfluidics, especially in connection with the miniaturization of biological tests. This know-how led to an interest in synthetic cells. He is the coordinator of the European project SIGSYNCELL: Engineering biological signaling pathways using synthetic cells.
• 2The project received funding from the European Union’s Horizon Europe programme under grant agreement No 101119961. It is one of the 104 projects selected for the doctoral networks call for proposals as part the 2022 Marie Sklodowska-Curie Actions: https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/opportunities/topic-details/horizon-msca-2022-dn-01-01.
• 3Including the CNRS, Université de Bordeaux, the University of Granada (Spain), Heidelberg University and the University of Münster (Germany), Wageningen and Delft Universities as well as AMOLF (the Netherlands), the University of Ljubljana (Slovenia), in addition to British partners such as University College London and Imperial College.
• 4Emulseo (France), Allozymes (Singapore), BPP (Germany), and DevelopDiverse.

What forms does SIGSYNCELL take?
J.-C. B. : SIGSYNCELL is a doctoral network funded by the European Commission via Marie Sklodowska-Curie Actions (MSCA), whose goal is training through research. The idea is to recruit twelve PhD students who will each work in a consortium laboratory, with an emphasis on researcher mobility. Their individual scientific projects are established based on the specializations of each research centre. Every student will spend part of their doctoral studies in another consortium laboratory, and PhD students will not be able to apply in countries in which they have already stayed for over a year. SIGSYNCELL thus encourages students to complete their PhD in countries that are new to them, thereby promoting European integration among partners and PhD students.

SIGSYNCELL has received a positive assessment from the European Commission, and we are in the process of completing the final negotiation phase, which is primarily administrative in nature. We will then recruit a “project manager” for early 2024 and begin selecting students, so that they can begin their PhD at the start of the following school year.

How is the CNRS’s coordination of SIGSYNCELL proceeding?
J.-C. B. : SIGSYNCELL is coordinated by the CNRS, but it remains a doctoral network: it is the universities that award the PhDs, especially Université de Bordeaux, which is a partner, and where I am a professor. All of the consortium’s members specialize in synthetic cells, and offer their know-how in creating and assembling specific compartments. The CNRS will provide overall coordination with a view to ensuring that advances remain compatible, that multidisciplinary knowledge is shared, and that training activities for students are effectively implemented.

This is important because there is a diverse set of expertise within the consortium. For example, my team works on microfluidic technologies, in other words microsystems in which we control liquids ( molecules concentration, flows) with extreme precision. Others will focus on creating membranes with pores that select the materials that can pass through them, or on controlling molecular conformations via light. Finally, systems will have to be developed for moving microcompartments, and for controlling their reactivity. These multidisciplinary aspects are the most important facet of the consortium on the scientific level. We will therefore marshal a wide range of expertise in order to work together jointly and effectively, all with the goal of providing high-level training through research for our recruited students.