Postdoc position (Wellcome Trust funded): Structural Basis of Autophagy Initiation

The Laboratory of Autophagy and Membrane Dynamics, led by Prof. Alex van Vliet, investigates the molecular architecture of cellular self-renewal. We aim to bridge the gap between biochemistry and cell biology by combining in vitro reconstitution with a multi-modal structural toolkit. Our lab uses a high-end pipeline—including Cryo-EM, HDX-MS/XL-MS, and Super-Resolution microscopy—alongside CRISPR/Cas9-engineered models. Our goal is to transform mechanistic insights into a blueprint for the autophagy initiation pathway, paving the way for targeted therapeutic strategies.
Relevant recent work includes: https://doi.org/10.1016/j.molcel.2022.10.017 , https://doi.org/10.1083/jcb.202507084

The Project:

Cells rely on autophagy—a sophisticated "self-eating" pathway—to degrade and recycle damaged or toxic materials. This process involves the dynamic, de novo formation of a double-membrane organelle called the autophagosome. While we know this system is critical for healthy aging and preventing neurodegeneration, we still lack a detailed molecular blueprint of the coordination required to build these organelles from scratch.

Our lab has recently uncovered novel mechanisms that link the autophagy machinery to specific selective cargoes, such as protein aggregates. This project builds on a foundation of exciting preliminary data. As a Postdoctoral Fellow, you will build on this foundation to characterize the structural and dynamic basis of how the early autophagy machinery targets and degrades these aggregates and organelles. Using a high-level "bottom-up" approach, you will reconstitute these signaling hubs in vitro to resolve the intricate protein-protein and protein-membrane interactions that drive autophagosome initiation.

Responsibilities

• Biochemical Reconstitution: Lead the design and execution of purification strategies to reconstitute multi-protein autophagy initiation assemblies from recombinant sources.
• Structural Proteomics: Employ advanced mass spectrometry techniques, specifically HDX-MS and XL-MS, to map protein-protein interfaces and the conformational dynamics of complex formation.
• High-Resolution Imaging: Determine the molecular architecture of initiation complexes using Single-Particle Cryo-EM, complemented by super-resolution fluorescence microscopy to bridge the gap between in vitro models and cellular contexts.
• Dissemination & Impact: Take a leading role in translating complex datasets into high-impact publications and presenting findings at international symposia.
• Innovation: Actively contribute to stakeholder engagement and identify opportunities for intellectual property (IP) development or the translational valorization of your structural discoveries.

Profile

• PhD in a Relevant Field: You hold a PhD in Structural Biology, Biochemistry, Biophysics, Cell Biology or a related discipline, with a track record of productivity.
• Structural Biology Toolkit: You have experience in Cryo-EM or HDX-MS methods and a demonstrated ability to interpret 3D protein structures to generate and test mechanistic hypotheses.
• In Vitro Reconstitution: You have experience in the purification of proteinsand an interest in building biochemical assays (experience with membrane mimetics (nanodiscs, liposomes) is a bonus)
• Analytical Mindset: You enjoy troubleshooting complex biochemical systems and have the computational literacy required for modern structural biology software (e.g., Relion, CryoSPARC, Pymol/ChimeraX).
• Communication & Drive: You are a proactive scientist who can work independently while thriving in a collaborative, multidisciplinary environment. You have good English communication skills, both written and oral.

Offer

• Ambitious Research Environment: A fully funded postdoctoral fellowship with flexible starting date, supported by the Wellcome Trust, in a lab with ample resources.
• Comprehensive In-House Facilities: Direct, in-house access to a structural biology suite, including:
  - Cryo-EM: Two dedicated 200kV microscopes for rapid screening and high-resolution data collection.
  - Structural Mass Spectrometry: On-campus HDX-MS platforms to map the dynamic landscape of your complexes.
  - Advanced Imaging: State-of-the-art super-resolution microscopy to bridge molecular structures with cellular localization.
• Integrated Workflow: All required facilities for protein expression (insect/mammalian), purification, and biophysical characterization are available in-house.
• Professional Development: A dedicated budget for international conferences and specialized workshops.
• Collaborative Ecosystem: Join a vibrant, multidisciplinary community of scientists focused on the mechanisms of cellular proteostasis.
• Mentorship & Career Development: We provide a supportive environment that balances high-level scientific mentorship with the opportunity to develop a unique technical and intellectual profile

Interested?

For more information please contact Prof. dr. Alex van Vliet, mail: [emailprotected].

In your application please include:

- Motivation letter (1page)
- Curriculum vitae
- Contact details of 2 referees

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