Four-dimensional self-assembly from peptides and DNA

ended

Structural organisation in living systems is both dynamic (varies with time), and emergent (more than the sum of its parts). Different blends of these aspects can be said to contribute to all the uniquely impressive processes of cellular biology. In contrast, synthetic self-assembled chemical systems rarely express each of these properties, being largely based on single self-assembly systems (e.g. DNA hybridisation or metal coordination), and static (i.e. observed at its thermodynamic minimum). This Fellowship will combine the Fellow's skills in chemoenzymatic peptide synthesis with those of the Supervisor in combining complementary self-assembly systems to obtain emergent superstructures. These studies will result in the first instances of dynamic and emergent self-assembly in synthetic chemical systems. To achieve this aim, we will perform chemoenzymatic polymerisation of peptides from the end of DNA backbones. Both units are capable of their own self-assembly - DNA through hybridisation, and peptides via secondary structures. In any 'static' snapshot of the system, the indirect interplay of DNA and peptide assembly will lead to highly unusual nanostructures. However, this work will go beyond, to measure the type and extent of self-assembly during the enzymatic polymerisation process using cutting edge techniques such as liquid-cell electron microscopy. The resultant systems will recapitulate the properties of living matter in these respects. In the course of these studies, the Fellow's professional skills will be honed through mentorship, the practice of taking a leading role in research, and through training courses offered by the Host Institution. At the end of the Fellowship, he will be ideally placed to assume an independent academic position.