Vlaams Instituut voor Biotechnologie (VIB)

Description How 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: Bachelor's degree in a relevant field (biological, biomedical, medical, natural sciences, mathematics or computer science), followed by; Master's degree or equivalent experience in molecular biology, cell biology, biochemistry, biomedicine, medicine, obtained no earlier than 01/03/2025. Basic programming experience and good statistical skills. A high-level analytical capability and an inquisitive mindset. Ability to define research goals and design an experimental plan. Motivation, adaptability, and team spirit. Excellent written and spoken English communication skills. Desirable skills: Experience working with next generation sequencing data or proteomics data Experience in wet lab molecular biological techniques. Programming experience demonstrated with good programming practice (maintaining code repositories, version control, R, Python). Experience in working with complex datasets. Interest in neurodegeneration and translational neuroscience. What we offer: A 2-year competitive doctoral scholarship and full benefits, renewable for two additional years following positive evaluation, although the applicant will be expected to actively seek independent funding and will be fully assisted in applying for personal fellowships, such as FWO Your monthly scholarship amount is calculated according to scholarship amounts for doctoral scholarship holders You will receive ecocheques, Internet-connectivity allowance and a bicycle allowance or a full reimbursement of public transport costs for commuting. You will do most of your work at Campus Drie Eiken in a dynamic and stimulating working environment. Find out more about working at the University of Antwerp here. The successful candidate will join an ongoing project between Jordanova and Varnai labs. He/she will be embedded both within an experimental and computational team. This interdisciplinary atmosphere has been the main catalyst for our recent joint success, such as obtaining the Generet Award for Rare Disease' 2025 managed by the King Baudouin Foundation (KBS), securing the funds for this position. Coaching in both experimental (iPSC culture, Drosophilagenetics, spatial omics) and computational (multi-omics integration, bioinformatics) approaches - a powerful combination offering unique opportunities for personal growth. The PhD student will benefit from extensive training opportunities and access to centralized facilities with expertise in genomics, functional genomics and cell biology, proteomics, microscopy, structural biology, technology development, and bioinformatics at VIB-UAntwerp Center for Molecular Neurology (), at VIB (), and at UBirmingham (). Opportunities for career development and networking. Opportunities for international mobility by spending time in the labs in Antwerp and Birmingham. Start date As soon as possible. How to apply Please submit your application through the VIB online application tool and be sure to include: A cover letter of max. two A4 pages, detailing your motivation to apply to this position, your research interests and previous research experience. A detailed curriculum vitae including a list of publications (if any). Names and contact information for two referees. The selection committee reviews all applications as soon as possible. As soon as a decision is made, we will notify you. If you have any questions about the job itself, please contact 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.