Introduction
Living cells form the basis of life. Cells have evolved to process an enormous amount of chemical signals using dedicated molecular networks. However, because of the high complexity of the living cell, unraveling the design principles of these molecular networks has proven impossible. In this project, we have built molecular networks outside of the living cell with the objective of studying the design principles of molecular networks using a bottom-up approach. Such an approach can provide detailed answers on the way molecular networks are able to process information. This is important for society as malfunctioning of molecular networks in living cells can lead to diseases such as cancer. In addition, these types of biomolecular networks could be used for sensitive diagnostics and molecular data storage.
Scientific Results
In the past 5 years, we have investigated several types of cell-free biomolecular networks, including i) cell-free gene circuits that can sense DNA and RNA inputs, ii) a DNA-based apoptosome mimic and iii) microcapsule colonies capable of scalable molecular communication. Our work, published in high impact journals like Nature Nanotechnology, Nature Catalysis and ACS Nano, has shown that elementary biological principles can be recapitulated under cell-free conditions. Because of the high level of control of these systems, fundamental design principles could be uncovered. For example, we have shown for the first time diffusive, multi-channel communication between semipermeable microcapsules (Nature Nano 2019). By building biologically inspired sender-receiver architectures, we have uncovered general design principles of cell-cell communication. In addition, we have also shown that these microcapsules can be used for DNA-based data storage. Next to this, we have also obtained fundamental insight on the working of the apoptosome, a large multi-protein complex that regulates cell death (Nature Catalysis 2020). Our experiments have revealed, for the first time, multivalent catalytic effects in the activity of crucial caspase enzymes.
Societal Results
Cell-free biomolecular circuits can be used in diagnostics. In the past five years, supported by an ERC PoC grant, we investigated their use in point-of-care miRNA diagnostics. In addition to this, we have discovered new materials that can be used to preserve DNA for DNA-based digital data storage.
