Project description
A synthetic cell offers cues about cell volume regulation
Maintaining an overall constant cell volume is critical for the function of microbial, animal and plant cells as it influences various biochemical parameters. Cells maintain their volume by regulating the movement of water across their membranes, through the energy-dependent transport of ions and compatible solutes. Moreover, mechanosensitive ion channels sense changes in cell volume and initiate cellular responses to regulate it. Funded by the European Research Council, the ABCvolume project aims to study the mechanisms of cell volume regulation by constructing a synthetic cell that comprises a minimal volume regulatory network. The focus will be on dissecting the involvement of a complex ATP- driven transporter and on the construction of a metabolic network for physicochemical homeostasis.
Objective
Cell volume regulation is crucial for any living cell because changes in volume determine the metabolic activity through e.g. changes in ionic strength, pH, macromolecular crowding and membrane tension. These physical chemical parameters influence interaction rates and affinities of biomolecules, folding rates, and fold stabilities in vivo. Understanding of the underlying volume regulatory mechanisms has immediate application in biotechnology and health, yet these factors are generally ignored in systems analyses of cellular functions.
My team has uncovered a number of mechanisms and insights of cell volume regulation. The next step forward is to elucidate how the components of a cell volume regulatory circuit work together and control the physicochemical conditions of the cell.
I propose construction of a synthetic cell in which an osmoregulatory transporter and mechanosensitive channel form a minimal volume regulatory network. My group has developed the technology to reconstitute membrane proteins into lipid vesicles (synthetic cells). One of the challenges is to incorporate into the vesicles an efficient pathway for ATP production and maintain energy homeostasis while the load on the system varies. We aim to control the transmembrane flux of osmolytes, which requires elucidation of the molecular mechanism of gating of the osmoregulatory transporter. We will focus on the glycine betaine ABC importer, which is one of the most complex transporters known to date with ten distinct protein domains, transiently interacting with each other.
The proposed synthetic metabolic circuit constitutes a fascinating out-of-equilibrium system, allowing us to understand cell volume regulatory mechanisms in a context and at a level of complexity minimally needed for life. Analysis of this circuit will address many outstanding questions and eventually allow us to design more sophisticated vesicular systems with applications, for example as compartmentalized reaction networks.
Fields of science
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural sciencesbiological sciencessynthetic biology
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural sciencesbiological sciencesgeneticsgenomes
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programme(s)
Topic(s)
Funding Scheme
ERC-ADG - Advanced GrantHost institution
9712CP Groningen
Netherlands