funcSOFI-PD · Quantitative super-resolution optical fluctuation and phase microscopy for structural and functional imaging of Parkinson's disease

Quantitative super-resolution optical fluctuation and phase microscopy for structural and functional imaging of Parkinson's disease

One of the big challenges today and in the future is the consequences of a population that is getting older. In 2030, 25% of the population in Europe are expected to be over 65, thus it is more likely that people develop neurodegenerative age-linked diseases like Alzheimer’s and Parkinson’s. Those diseases have a huge impact on quality of life and to date, therapies can only treat the symptoms. Oligomerization and aggregation of the protein α-synuclein is a hallmark of Parkinson’s disease. However, the underlying molecular mechanism of cellular dysfunction due to toxic forms of this protein remains unclear. The overall objective of this project was to investigate alpha-synuclein (α-syn) aggregation in Parkinson’s disease compromised neurons using advanced microscopy techniques. I suggested to develop and apply multicolour 3D quantitative fluorescence super-resolution optical fluctuation imaging (SOFI) and label-free phase microscopy in a multiplane microscope setup. The goal was to use this new imaging concept(s) (1) to follow α-syn aggregation over time at the cell membrane and in the cytosol and (2) to uncover the induced cytoskeleton alterations in mouse primary hippocampal neurons. Ultimately, the molecule-specific readout based on SOFI was be complemented by (3) label-free, quantitative phase imaging of dynamics and overall cell morphology at extremely high imaging speeds. I am a biophysicist with a specialization in single molecule spectroscopy and in my PhD I worked on using photon statistics for molecular counting. This fellowship has expanded my quantitative microscopy expertise to 3D imaging while enlarging my biological scope to neurodegenerative diseases. I could successfully develop novel tools for advanced microscopy and apply them to monitor the interplay of cytoskeleton and protein aggregation in Parkinson's disease. I could also extend my personal competences by managing the project, following complementary skills courses, and organizing public outreach activities (e.g. study week for high-school students). While performing interdisciplinary research on neurodegenerative disease, I could strengthen my research profile to further enhance the European research landscape.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз