From a polymer chemistry perspective, the way in which nature produces its plethora of different proteins is a miracle of precision: the synthesis of each single molecule is directed by the sequence information chemically coded in DNA. The present state of recombinant DNA technology should in principle allow us to make genes that code for entirely new, very sophisticated amino acid polymers, which are chosen and designed by man to serve as new polymer materials. It has been shown that it is indeed possible to make use of the protein biosynthetic machinery and produce such de novo protein polymers, but it is not clear what their potentials are in terms of new materials with desired functionalities.
I propose to develop a new class of protein polymers, chosen such that they form nanostructured materials by triggered folding and multimolecular assembly. The plan is based on three innovative ideas: (i) each new protein polymer will be constructed from a limited set of selected amino acid sequences, called modules (hence the term modular protein polymers) (ii) new, high-yield fermentation strategies will be developed so that polymers will become available in significant quantities for evaluation and application; (iii) the design of modular protein polymers is carried out as a cyclic process in which sequence selection, construction of artificial genes, optimisation of fermentation for high yield, studying polymer folding and assembly, and modelling of the nanostructure by molecular simulation are all logically connected, allowing efficient selection of target sequences.
This project is a cross-road. It brings together biotechnology and polymer science, creating a unique set of biomaterials for medical and pharmaceutical use, that can be easily extended into a manifold of biofunctional materials. Moreover, it will provide us with fresh tools and valuable insights to tackle the subtle relations between protein sequence and folding.