As part of a collaboration between two different groups in chemistry and biochemistry, Thom Sharp presents here his thesis work on the development of new methods for cryoelectron microscopy. Throughout his Ph.D., Thom had to master a whole range of techniques including modelling, molecular biology and microscopy. Using these skills to tackle an outstanding problem, the pursuit of high-resolution structures of peptide-based materials, Thom highlights in this thesis his newly developed methods for analysing and processing this particular type of electron microscopy data. This thesis gives the first molecular description of a de-novo designed peptide-based material. In general, this research will have a huge impact on the peptide assembly field, and also in electron microscopy as it introduces new methods and approaches, all of which are Thom's inventions and are described in this thesis.

Thom Sharp completed his bachelor¿s degree in Biochemistry at the University of Bristol, with a year spent a year working at AstraZeneca. He continued in Bristol for his PhD in bionanotechnology, which was performed under the supervision of Dek Woolfson, a protein design chemist, and Paul Verkade, an electron microscopist. Thom is currently at the University of Oxford, where he is developing DNA-templated protein arrays to increase the throughput of single-particle analysis.

Introduction.- Biomolecules & Microscopy.- Materials and Methods.-Experimental Methods.- Imaging Methods.- Experimental Results.- Towards an Atomistic Structure of a De Novo Designed Peptide Fibre.- Developing Novel Probes for Correlative Light Electron Microscopy.- Conclusions and Appendices.- Concluding Remarks.- Abbreviations.- Amino Acid Structures.- Vectors, Primers and Recipes.