CHEMISTRY FOR THE GENERATION OF ARTIFICAL BIOLOGICAL SYSTEMS
Synthetic biology, in vitro evolution, modified nucleic acids, modified proteins, cell-free systems.
Marcel HOLLENSTEIN (Institut Pasteur, Paris, FR)
Vincent NOIREAUX (University of Minnesota, Minneapolis, USA)
Pasquale STANO (University of Salento, Lecce, IT)
Cells represent the smallest structural and biological units of all living organisms. However, these entities display an enormous complexity, whose understanding can be approached in different ways. A relevant approach focuses on chemistry and its philosophy of building. Constructing molecules and molecular systems gives the opportunity of exploring the features and the recognition/reactive patterns that characterize molecules, networks and systems of increasing complexity. Moreover, it allows designing and tailoring reaction pathways, modelling specific aspects of living systems, and producing novel biosystems or hybrid bio-chemical systems. Such a vision, fundamentally linked to chemistry, is now emerging as a branch of synthetic biology - often called bottom-up synthetic biology. In this context, two emerging topics are under strong expansion: (1) cell-free systems and (2) expansion of the genetic code. Both heavily rely on chemistry-biology integration.
(1) Cell-free systems have been traditionally used in biochemistry to unveil mechanistic details of biological processes. Chemical synthetic biology uses cell-free systems as powerful alternatives to living cells to engineer systems for specific purposes. Cell-free systems are versatile tools for fundamental and applied studies. They can be realized in the test-tube or can be micro-compartmentalized (e.g., in microfluidic devices or microcompartments) to achieve new promising technologies such as the bio-organic synthesis of drugs, proteins and peptides from non-natural amino acids, biochemical chip based on genetic circuits, biosensors, and ultimately the construction of synthetic cells for nanomedicine or to face the Grand Challenge of life origin on Earth. Cell-free technologies calls for a new blend of chemistry, biochemistry, microfluidics and numerical modelling, and promise applications in the medium-short term. Genetic circuits of increasing sophistication have been reported and characterized in all details. The combination of cell-free systems with micro-compartment aims for the construction of "minimal cells" in the laboratory, with several already-reported important examples. No doubts current efforts on cell-free systems design and construction will impact on next-generation biotechnologies.
(2) Natural biopolymers (nucleic acids, proteins, and peptides) represent the fundamental building blocks of biological structures and functions. Chemical modification of natural biopolymers for the crafting of novel entities with hitherto unknown structures and functions has been a central aim of synthetic biology. 4 Technologies such as amber codon suppression and Darwinian in vitro evolution have revolutionized the field of synthetic biology. Indeed, a vast diversity of unnatural amino acids could be incorporated into mammalian cells and even into model organisms, providing in cell tools for the monitoring and imaging of the progression of diseases. Moreover, engineered polymerases have been developed to accept a broad range of modified nucleotides which enabled the identification of DNA and RNA sequences capable of binding specifically to targets or catalyse reactions such as the replication of their own encoding sequences. Thus, the symposium will also focus on some aspects of the evolution of proteins and peptide with an expanded genetic code and the generation of chemically nucleic acids displaying properties that markedly deviate from their natural functions.
Overall, this symposium will give an overview of the various chemical approaches currently used in cell-free synthetic biology and in the evolution of unnatural biopolymers.