PhD position in the role of TDP-43 aggregation in Neurodegeneration

TDP-43 aggregation is the major hallmark of nearly all amyotrophic lateral sclerosis (ALS) forms and half of frontotemporal dementia (FTD) cases. Two leading labs are teaming up and combining their expertise to decipher the molecular underpinnings of TDP-43 aggregation. The Da Cruz lab has innovative cellular systems that recapitulate human TDP-43 pathology as seen in patients and the SWITCH lab has unraveled the importance of heterotypic interactions in amyloid proteins. These tools will be powerfully combined in this project to investigate specific (heterotypic) interactions between the aggregation-prone regions of TDP-43 and the background proteome and to determine which cells are most sensitive to TDP-43 aggregation.

This hypothesis will be tested by performing a genome-wide CRISPR and compound screen in a reporter cell line and followed by computational modelling.  The most promising hits will then be validated using a combination of biophysical and biochemical techniques as well as cellular functional assays relevant to disease. You will learn to produce disease-aggregation prone-protein including TDP-43 aggregates recombinantly, as well as isolate them directly from the brains of animal models and human donors. The seeding capacity of TDP-43 aggregates will be studied comprehensively in vitro, in cells, and in animal models.

The SWITCH Laboratory, part of the KUL Department of Cellular and Molecular Medicine and the VIB-KU Leuven Center for Brain & Disease Research, is one of the leading laboratories in human disease-related protein aggregation. It is an interdisciplinary workplace, bringing together about twenty-five researchers from different backgrounds, such as bioinformatics, biophysics, and cell biology. SWITCH has a unique platform of technologies for studying protein aggregation, including biophysical, ultrastructural, and cell biological instrumentations. 

For a primer on who we are, what we do, and our latest publications, see http://www.switchlab.org/

The Da Cruz Laboratory, part of the KUL Department of Neurosciences and the VIB-KU Leuven Center for Brain & Disease Research investigates disease mechanisms for therapy development to ultimately treat ALS and FTD. We focus on the role of local axonal translation and liquid-liquid phase separation/aggregation as well as the spreading of disease-associated RNA binding proteins TDP-43 and FUS in axonal/synaptic maintenance and loss. To unravel novel disease targets, we combine sophisticated mouse models, and human stem cell and genome editing approach to model ALS and FTD, together with state-of-the-art spatial omics technologies and high-resolution microscopy. We are a stimulating international team bringing together postdocs, Ph.D. and Master students, and lab technicians. 

See https://dacruzlab.sites.vib.be/en to learn more about us.

• You hold an M.Sc. or M.D. degree, with minimally distinction grades or higher.
• You meet the English language criteria of KU Leuven
• You have a strong interest in protein aggregation and neurodegenerative diseases
• Highly motivated, enthusiastic, critical, and creative
• The ability to work in a multidisciplinary team is a must
• Prior experience with high content analysis is a plus
• You are willing to work with patient tissue and conduct animal experiments (Felasa B certificate is a plus)

• A versatile and challenging job
• A vibrant, world-class research environment operating at an international level
• Access to the resources of two host institutions:
  • VIB an excellence-based research institute
  • KU Leuven , one of Europe’s leading research universities
• State-of-the-art research facilities . 
• A dedicated training program  to broaden your expertise and enhance your skillset

Starting Date: as soon as possible

For more information contact hannah.wilkinson@kuleuven.be. Please complete the online application procedure and include a detailed CV including a list of publications, a motivation letter, and the contact information of three referees.

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