High Throughput Screening and Image Analysis for Parkinson’s Disease


CALL: 2014

DOMAIN: BM - Regenerative Medicine in Age-related Diseases

FIRST NAME: Siddharth




HOST INSTITUTION: University of Luxembourg

KEYWORDS: High Throughput Screening, Image Analysis, Automated Microscopy

START: 2014-07-01

END: 2015-06-30

WEBSITE: https://www.uni.lu

Submitted Abstract

Parkinson’s disease (PD) affects about 1-3% of the population over the age of 65 years and is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra. In genetic studies of familial versions of PD, mitochondrial dysfunction is identified as a general hallmark of PD that is coupled to many phenotypic disease traits. Neurons in particular depend significantly on mitochondrial integrity for survival because they have to keep large concentration gradients across their cell membrane by ATP consuming ion pumps. Hence mitochondria as the main energy generators of the cell are crucial for neuronal functionality. Several studies have shown the association of mitochondrial dysfunction with PD and it is a common feature of neurodegeneration. However, despite these comprehensive studies, the mechanism for the central role of mitochondrial dysfunction in PD is not well understood. The significantly large length of neuronal axons in general and in particular of neurons in the substantia nigra poses special challenges for mitochondrial distribution and energy transport to extreme cellular regions. As a result, mitochondrial trafficking is a recently emerging and important area of research in relation to PD.Given the critical role of mitochondrial distribution in PD, we propose to study mitochondrial trafficking with the aid of high throughput/high content imaging for longitudinal studies of patient derived iPS cells and related differentiated neurons. In this context, the project objectives can be summarized as follows:(1) Deployment of an automated, robotic microscope for imaging longitudinal studies of neuronal growth (2) Development of automated image analysis algorithms for the study and quantification of mitochondria trafficking The use of an automated robotic microscope provides the advantage that multiple experiments can be conducted simultaneously. The large amounts of imaging data generated by such a system necessitates the development of automated tools for image analysis and management. These longitudinal studies combined with automated analysis has the potential to significantly enhance our understanding of mitochondrial dysfunction in neurons and consequently it’s involvement in Parkinson’s Disease.

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