There is a potential link between neurodegenerative diseases and disordered proteins forming amyloids, which subsequently trigger calcification of brain tissues. In our research laboratories, we have discovered indicative calcification patterns occurring in pineal glands of Alzheimer’s disease (AD) and frontotemporal degeneration patients (Figure 1). However, there is still a great lack of knowledge on the role of protein disorder and organic-inorganic interactions in brain calcifications.
a) Investigate protein conformations and mechanisms at the molecular level within brain tissues including the pineal glands of AD patients compared to healthy controls.
b) Carry out further sophisticated high-resolution imaging and proteomics techniques to study the structure of the organic-inorganic interface of the brain calcification.
c) DNA isolation from pinealocytes, astrocytes, and glial cells to understand the mechanisms of calcification.
d) Fabricate in-vitro models based on proteins derived from brain tissues to investigate calcification at multiple length scales.
Laser capture microdissection (LMD) and proteomics.
High-resolution electron microscopy, material development.
Protein conformation studies: Circular Dichroism, Fourier Transform Infra-Red imaging, Dynamic Light Scattering.
Year 1– Study proteomics and gene expression on diseased tissues (LMD) alongside with advanced imaging techniques to characterise calcification in tissues in pineal glands and brain.
Year 2– Analyse the extracted proteins from diseased and healthy tissues and isolate RNA from specific areas around calcification.
Year 3– Employ epigenetic approaches to investigate the cells surrounding the calcified tissues.
Year 4– Synthesise proteins that are identified in diseased tissues and create in-vitro models for calcification.