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Regime: Full-time Let’s shape the future - University of AntwerpThe University of Antwerp is a dynamic, forward-thinking, European university. We offer an innovative academic education to more than 20000 students, conduct pioneering scientific research and play an important service-providing role in society. We are one of the largest, most international and most innovative employers in the region. With more than 6000 employees from 100 different countries, we are helping to build tomorrow's world every day. Through top scientific research, we push back boundaries and set a course for the future – a future that you can help to shape. PhD Position: Spatial Omics Meets Neurodegeneration — Mapping Therapeutic Targets in Charcot-Marie-Tooth NeuropathyPositionHow do you go from a patient nerve biopsy to a therapeutic target for a neurodegenerative disease with no cure? That's exactly what this PhD study is about. We have a unique entry point into this type of research: actual nerve biopsies from patients with Charcot-Marie-Tooth neuropathy due to YARS1 mutations, along with matching iPSC-derived motor neurons and Drosophila models. Now, we need a curious and driven PhD candidate to help us analyze these samples using spatial multi-omics. This is a joint project between Prof. Albena Jordanova (VIB-UAntwerp, Belgium) and Assist. Prof. Csilla Varnai (University of Birmingham, UK), funded by the Generet Award for Rare Diseases’ 2025 (King Baudouin Foundation). Charcot-Marie-Tooth disease (CMT) is an incurable hereditary neuropathy that causes the degeneration of peripheral nerves. This disease leads to muscle weakness, sensory loss, and lifelong disability. A particularly enigmatic subtype of CMT is caused by mutations in aminoacyl-tRNA synthetases (aaRS). These mutations do not always impair the enzymes’ canonical, ubiquitous functions but instead induce neomorphic activities, such as aberrant transcriptional regulation (Bervoets et al., Nature Communications 2019) and cytoskeletal remodeling (Ermanoska et al., Nature Communications 2023). However, the exact mechanisms by which these activities converge and translate into axonal degeneration restricted to the peripheral neurons remain unclear. We are trying to fill this knowledge gap by studying the tyrosyl-tRNA synthetase (YARS1), charging tRNA with tyrosine in the first step of protein biosynthesis. The Jordanova lab first described that dominant mutations in YARS1 cause CMT (Jordanova et al., Nat Genetics 2006) and linked the enzyme’s non-canoncial functions to neurodegeneration. To gain better insights in disease pathology, the lab also generated the first Drosophila, yeast and iPSC models for this neuropathy (Storkebaum et al, PNAS 2009). Project:This project aims to uncover the mechanisms by which YARS1 mutations drive peripheral nerve degeneration. We hypothesize that mutant YARS1 exerts compartment-specific toxicity, ultimately leading to axonal degeneration in a manner shared across aaRS-linked CMT. To test this, we will perform high resolution spatial transcriptomics and proteomics analyses in unique nerve biopsies and iPSC-motor neurons derived from YARS1-CMT patients. Multimodal bioinformatics processing of the omics datasets will guide selection of differentially regulated key genes to be evaluated for their therapeutic potential in our YARS1 Drosophila and iPSC models. Guided by the unmatched context of the affected human tissue, and the power of our experimental models, this work will deliver urgently needed insights into the pathogenesis of YARS1-CMT. The project may also reveal shared mechanisms and therapeutic targets relevant to other aaRS-associated neuropathies and other peripheral nerve disorders. Profile:Essential requirements:
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Start date:As soon as possible. Want to apply?
Diversity & Inclusion:We are committed to creating and sustaining an inclusive, respectful and collaborative environment. We value diversity in all its forms, e.g. gender identity, ethnicity, nationality, disability, sexual orientation, age, socio-economic background, and family situation. We welcome applications from individuals of all backgrounds and identities, and we are dedicated to providing equal opportunities and actively promoting a culture of belonging. We believe that a diverse and inclusive workplace is essential for scientific creativity and growth, effective collaboration, and impactful discoveries.
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