Chemical and biological approaches to sequence controlled polymers

Sequence controlled polymers (SCPs), linear macromolecules whose chemical and physical properties can be programmed with atomic-scale resolution, promise technological breakthroughs in novel materials, nanotechnology, and medicine. This technological promise provides ample motivation for development efforts towards their synthesis. However, at this time we are only able to synthesize limited kinds of SCPs, and our methods lack efficiency and they do not approach the accuracy, reproducibility, and control found in Nature. To address this challenge, this proposal describes the development of chemical (ring open polymerization) and biological (evolution of the translation apparatus) methods for the cost-effective and high yielding synthesis of sequence-defined vinyl polypeptides. Vinyl amino acids will be synthesized and incorporated into natural polymers, endowing biopolymers with new chemical functionality and serving as a model for synthetic of more complex template-directed SCPs.

Imagine the possibilities of producing evolvable, structurally broad synthetic polymers that meld the accuracy and reproducibility of biology with the complexity and diversity of chemistry. The biosynthetic route for producing SCPs pursued in this proposal could ultimately enable the synthesis of new molecule classes not readily attainable by chemical methods, as well as the exploitation of genetically encoded evolution in the search of living materials and biophysical probes. This would result in a paradigm shift in materials discovery and research. Beyond research impact, the US-UK team will establish and maintain a valuable network that provides for competitive, interdisciplinary, and globally-engaged research. This network will train the next cadre of whole-brain materials researchers who are comfortable operating between disciplines (e.g., chemistry and biology), labs, and continents. While the fundamental nature of this work make it too early stage for the involvement of multidisciplinary external collaborators or industrial partners, the impact of the work is expected to be wide ranging with many beneficiaries. Specifically: Researchers in several areas will benefit from this research. Those in directly related fields such as polymer chemistry and self-assembly will benefit from the gained and shared knowledge generated and published/presented outputs. Additionally however, researchers in wider fields such as biological sciences and in the medical/pharmaceutical sciences will also benefit from this work given the fundamental understanding and also potential applications of such new materials. In this area in particular, ultimately it is envisaged that this work will go on to directly impact both the public and the host countries economies. Obviously to achieve this, engagement with collaborators in other disciplines and engagement with industrial partners will be required. The investigators are well placed to deliver these new research areas and are poised to connect the research to appropriate outlets. Wider benefits of the project include the training of new Ph.D. researchers in the exciting and current area of materials chemistry and synthetic biology that will provide them with an excellent background for further studies and hence potential contribution to the scientific communities and UK and US economies in the future. The investigators will also benefit greatly by the opportuntiy to generation high impacting research as outlined in the proposal. The proposed collaboration will serve to increase the global orientation of both the researchers involved in the work and the research groups of Jewett and O'Reilly. The project also aims to connect with and therefore benefit the general public through outreach, primarily geared towards school age children to communicate the potential benefits of the ultimate technologies and enthuse a new generation about the potential benefits of the chemical and material sciences. Moreover, by exploring differences between outreach education programs in the US and the UK, the network will be of great use in engaging public interest and educating and impacting policy makers. A particular focus is women in science and we use the transatlantic collaboration to inspire and encourage women in the field of science and especially those at the interface of biology, engineering and materials.