About the Project
Bone is a multi-functional mineralized tissue which provides mechanical support for the body, generates motion and protects organs. A number of diseases can affect ageing bone, including osteogenesis imperfecta and osteoporosis. Despite the fact that a large number of studies have focused on mechanical properties of bone, there is still a lack of understanding with regard to the structural and mechanical changes in the bone matrix during diseases at micro- and nano-scales.
The zebrafish (Danio rerio) has been well recognized as an ideal animal model system for studying developmental processes and human pathology because it possesses high genetic similarity to humans. Furthermore, development of zebrafish models contributes to the reduction, replacement and refinement (3Rs) of animal experiments, for example, by reducing the use of rodent models. Recently, researchers have successfully utilized zebrafish models for exploring numerous pathologies including heart disease, muscle disease and central nervous system disorders. However, information on how to model human bone diseases using zebrafish is absent in the literature. Hence, there is an urgent need to develop a systemic method for characterizing nanoscale structural and mechanical properties in zebrafish with applicability for modelling human bone diseases. In this project, a number of high spatial resolution techniques will be applied to study the multi-scale structural features and mechanical properties of healthy and diseased zebra fish. To determine the disease dependent topographical and biomechanical alterations, we will employ advanced atomic force microscopy (AFM) based PeakForce Quantitative Nanomechanical Mapping (PFQNM) technique to investigate nano-scale changes associated with diseases in zebrafish spine bone.
PFQNM enables the co-localization of ultrastructural and mechanical properties with a high
resolution. Optical microscopy, SEM and TEM will be utilized to observe the nano-/micro-structure of diseased bone and mineralized tissues focusing on the collagen fibrils and mineral crystallites. Furthermore, advanced synchrotron radiation techniques in National Synchrotron Radiation Research Center (NSRRC) in Taiwan, will be used such as transmission X-ray microscopy (TXM), ultra-high resolution CT scans, in situ experiments will be conducted with these facilities.
Applicants must have a good MSc or MEng degree in engineering, materials science, physics or an associated field. It is expected the successful student will 2 years at NTHU, Taiwan and 2 years at University of Liverpool, UK.
When applying please ensure you Quote the supervisor & project title you wish to apply for and note ‘NTHU-UoL Dual Scholarship’ when asked for details of how plan to finance your studies.
Funding Notes
This project is a part of a 4-year dual PhD programme between National Tsing Hua University (NTHU) in Taiwan and the University of Liverpool in England. It is planned that students will spend equal time studying in each institution.
Both the University of Liverpool and NTHU have agreed to waive the tuition fees for the duration of the project and stipend of TWD 10,000/month will be provided as a contribution to living costs.
References
[1] P-Y. Chen, D. Toroian, P.A. Price, J. McKittrick. Minerals form a continuum phase in mature
cancellous bone, Calcif. Tissue Int. 88, 351-361 (2011).
[2] P-Y. Chen, J. McKittrick. Compressive mechanical properties of demineralized and
deproteinized cancellous bone, J. Mech. Behav. Biomed. Mater. 4, 961-973 (2011).
[3] R. Akhtar, M.J. Sherratt, J.K. Cruickshank, B. Derby, Characterizing the elastic properties
of tissues, Materials Today, 14, 96-105 (2011).
[4] R. Akhtar, M.R Daymond, J.D Almer, P.M Mummery, Lattice strains and load partitioning in
bovine trabecular bone, Acta Biomaterialia, 7, 716-723 (2011)
[5] M.A. Meyers, J. McKittrick, P-Y. Chen, Structural Biological Materials: Critical
Mechanics-Materials Connections, Science, 339, 773-779 (2013).
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