Revealing the 3D nanoscale structure and composition of healthy and diseased bone and teeth

A central goal of this Overseas Travel Grant proposal is the establishment of a network of leading researchers with expertise in bone and tooth formation who share the believe that a comprehensive understanding of the nanoscale organization of both mineral and organic phase is at the heart of the development of new approaches for medical treatments. The proposed methodology is making use of the advancement of high-resolution electron imaging and spectroscopy to gain insights into the 3D structure and composition on the nanoscale. This approach is of great importance for a full understanding of the mechanisms behind structure formation and potential failure mechanisms in bones and teeth.
In a recent publication (Reznikov et al., Science 2018) we were able to identify 12 levels of organisation in bone from the nano- to the macroscopic scale with a self-similar organisation pattern emerging across the different length-scales. These findings indicate the importance to understand the structure of mineralised tissue on the nanoscale.
Based on this work I aim to explore the application of nanoscale imaging using advanced electron microscopy and spectroscopy to mineralised tissue such as bone cells and teeth.
In both cases it is highly exciting to gain a full image of the mineral/organic assembly in healthy and disease affected tissues.
The complex interplay between the mineral and the organic phases in bones and teeth appears to strongly affect the properties of the resulting biomineral with significant effects of disruptions on the nanoscale due to mineralisation affecting diseases (e.g. osteogenesis imperfecta or amelogenesis imperfecta, osteoporosis, arthritis). Hence, this work will provide a platform for future collaboration with leading life scientists and clinicians and will enable to link the high-resolution information gained by the chosen approaches with diagnostic observations.
Both hosts at McGill University in Montreal and University of Connecticut in Hartford provide ideal conditions for both training and research since they have an excellent international reputation on health related materials research and provide access to an outstanding set of experimental techniques to achieve the goals of this proposal.

Diseases affecting mineralising tissue such as bone and teeth are important and are becoming increasingly common in our ageing society, resulting in significant costs for the NHS and reduced quality of life for affected individuals. These diseases modify the structural and mechanical properties of bone (e.g. arthritis or osteporosis) and teeth (e.g. amelogenesis imperfecta or chalky teeth), which depend on the nanoscale structure and composition of mineralised collagen. This project will develop novel approaches to assess the tissue structure and composition with ultimate spatial resolution. Thus it has strong potential for impact on academic and industrial researchers working in the area of musculo-skeletal and dental disorders, on the wider public, and also on the UK economy.
The relevance of this work is highlighted by the fact that both institutions involved, McGill University and University of Connecticut, highly reputable organisations with a long tradition in researching mineralising tissue and cells, will provide full and free access to state-of-the-art research facilities to enable the applicant to develop new skills in biomineralisation related electron microscopy and spectroscopy, to make use of his long track-record of the physical-sciences based materials characterisation and to establish novel interdisciplinary and international links at the Physical Sciences/Life Science interface.

Immediate impact will be obtained through the training of the applicant and other researchers involved at the involved institutions. The highly interdisciplinary nature of this research area will encourage scientists to develop a flexible approach to problems and skills in working with people in different fields towards a common goal. New methods of working together developed during this grant. The knowledge gained throughout this work will be made available to the academic and industrial communities through conferences, websites and networks.

This project lends itself to impact through public engagement and outreach. York have well-established outreach programmes. These include an annual Festival of Sciences (where local schools take part in educational workshops related to science and engineering); presentations for teachers and sixth formers and highlight seminars.