PhD student for experimental neuropathology and cell biology in amyotrophic lateral sclerosis (ALS)

KU Leuven
August 22 2017
Position Type
Full Time
Organization Type

For the Laboratory for Neuropathology we are looking for a PhD student for experimental neuropathology and cell biology in amyotrophic lateral sclerosis (ALS) The Laboratory of Neuropathology, focusing on the pathogenesis of neurodegenerative disorders, is a growing laboratory in the research group of Experimental Neurology (Neuroscience Department). This research group has a close collaboration with the Neurology Department of the University Hospitals Leuven with about 50 researchers in different domains.

For studying amyotrophic lateral sclerosis (ALS) we are starting a project together with the Laboratory of Neurobiology, which is also part of Experimental Neurology. In addition, this laboratory is one of the research groups of the VIB KU Leuven Center for Brain & Disease Research (CBD). There are 13 research groups within the CBD with a total employment of 230 researchers.

KU Leuven funding is available for the next 4 years for a project focusing on the composition and biological impact of protein aggregates in ALS throughout the evolution of the disease and among the different types of the disease (e.g. C9ORF72-related ALS). To identify steps of different types of protein aggregate maturation human brain samples will be analyzed biochemically and neuropathologically. The biological effects (e.g. on nucleocytoplasmic transport) and toxicity of the aggregates will be tested in cell culture systems of human-derived induced pluripotent stem cells (iPSCS).

With these observations, we want to improve the knowledge about protein aggregates in ALS and their biological effects and to identify novel targets for disease treatment.

Amyotrophic lateralsclerosis (ALS) is a rare neurodegenerative disorder that leads over time to amore and more severe loss of motor function. The reason for this loss of motorfunction is that the motor neurons in the spinal cord as well as the primary motorneurons in the precentral gyrus degenerate. Although other proteins can alsorepresent pathological correlates of ALS most frequently aggregates of TDP43were found in cases of sporadic but also of familial ALS (Mutations in theTDP-43-related gene, hexanucleotid mutations in the C9ORF72 gene).

In this project wewill determine the composition of TDP43-aggregates (truncated and modifiedforms of TDP43 and non-TDP43 proteins that are associated with the aggregates) in human tissue samples from sporadic and C9ORF72 mutant ALS brains and spinal cords and test the biological/ pathobiological effects of distinct aggregates as well as potential signs of toxicity in cell culture. The cell culture systemsthat will be used is an iPSC-derived system of human cell lines. In these cell lines distinct proteins can be genetically manipulated to learn more about the functional insights of TDP43-aggregate-related effects on cells.

Project tasks:

- Biochemical protein analyses of human samples (Western blot analyses, SDS PAGE, immunoprecipitation, mass spectrometry)

- Pathological analyses of human brain tissue

- Cell culture and biochemical and morphological analysis of the cells.

This job comes from a partnership with Science Magazine and Euraxess