This PhD project will involve the synthesis and characterization of innovative fluorescent sensors for specific amyloid proteins implicated in neurodegenerative disorders. The developed probes will then be applied in super-resolution microscopy that offers nanometre-scale resolution. The PhD candidate will work with exciting synthetic and analytical techniques, and cutting-edge imaging technologies in a dynamic and interdisciplinary research environment at the School of Medical Sciences, Faculty of Medicine and Health, University of Sydney.
Misfolded proteins assemble into macromolecular structures called amyloids, which have been implicated in a range of neurodegenerative diseases such as Alzheimer's disease. To date, numerous questions remain to be answered, such as, what is the interaction of amyloid species with the cellular machinery? Which species are responsible for cell death? What are the structural and behavioural differences between pathogenic amyloids and the more recently identified functional amyloids? The answers to these questions lie at the nanometre-scale. Traditional fluorescence microscopy techniques are limited by optical diffraction, examine ensemble behaviour and provide no insight into protein aggregation and its impact on other cellular factors. Therefore, tools and technologies that enable nano-scale visualisation of the molecular, structural and physiological interactions of functional and pathogenic amyloids are highly sought after. Nobel Prize-winning super-resolution microscopy techniques have revolutionised the nanoscale imaging and study of biological and synthetic nanostructures by breaking the diffraction limit of light. In our research group we explore innovative approaches to develop fluorescent sensors for nano-scale imaging of amyloid structures. Molecular-scale understanding of amyloid behaviour will open new doors to develop early diagnosis of neuropathologist and design effective therapeutic interventions. In this multi-disciplinary research project we collaborate with research groups with expertise in amyloid biology (Prof. Margaret Sunde) and Neuropathology (Prof. Jillian Kril).
Skills you will develop in this project include: chemical synthesis and characterisation, fluorescence spectroscopy, high-throughput biochemical assays, protein expression and purification, fluorescence microscopy and super-resolution microscopy. The project is supported by an Australian Research Council (ARC) project grant. We offer a range of projects depending on students interests and I encourage students with interests in Chemistry, Biochemistry, Neuroscience or Molecular imaging to contact me.
The opportunity ID for this research opportunity is 2945