PhD Position: does Autophagy degrade toxic cargo

Company description

The Laboratory of Autophagy and Membrane Dynamics, headed by prof. Alex van Vliet, is part of the department of Cellular and Molecular Medicine at KU Leuven. We aim to uncover molecular mechanisms of autophagy initiation and membrane dynamics by combining in vitro reconstitution, structure-function studies, biochemistry and cell biological approaches. We are seeking a highly motivated PhD candidate to investigate the molecular mechanism of how selective autophagy targets cargo in the context of toxic aggregate or organelle buildup.

Our lab has a strong track record in uncovering the mechanistic details of biological processes using diverse experimental systems. We apply state-of-the- art technologies, including high-resolution fluorescence microscopy, quantitative proteomics (HDX and XL MS), (cryo-)electron microscopy analysis, and advanced cellular assays utilizing Crispr/Cas9 tagging. Our mission is to translate these mechanistic discoveries into a detailed understanding of the autophagy initiation pathway, advancing knowledge of its cellular regulation and paving the way for novel therapeutic strategies.

How do our cells stay healthy? Human neurons are post‑mitotic and thus have to survive for decades. To do this, they rely on a system of self‑eating termed autophagy to degrade and recycle damaged and/or toxic material. This system, whereby a new organelle termed an autophagosome is dynamically formed to engulf cellular material, is critical for cellular health and healthy ageing.

The process is hierarchical and can be understood as a sequential process, where key protein complexes and signalling hubs coalesce to initiate autophagosome formation. How cells coordinate this intricate machinery required to create an autophagosome is still not fully understood, and this lack of knowledge is impeding progress in understanding how autophagy is able to prevent the toxic buildup of aggregates in neurodegeneration, or fails to clean up damaged mitochondria in ageing.

Our work has uncovered new potential mechanisms required for selective autophagy and how the autophagy machinery links up with cargoes including aggregates. In this project, the PhD candidate will build on a strong foundation of existing data to characterise the degradation of aggregated proteins or organelles. The candidate will utilise state‑of‑the‑art methodology and combine in‑vitro reconstitution, protein biochemistry, electron and fluorescence microscopy and CRISPR/Cas9 genome editing to study the role of the early autophagy machinery in targeting and degrading protein aggregates and organelles.

These studies will initially be performed in tractable cell lines to leverage insights gained in the molecular mechanism of protein complex formation, before moving into an iPSC‑derived neuronal model and patient samples.

• Master's degree in Biochemistry, Cell Biology, Molecular or Structural Biology, Biological/Medical Sciences, or a closely related field.
• Critical thinking and ability to think about experimental design, analyze data rigorously, and solve technical problems proactively.
• Good verbal and written communication skills and fluency in English.
• Rigorous, organized, and proactive with a collaborative mindset and enthusiasm to work in an international and interdisciplinary environment.

• Experience with fundamental molecular and cell biology techniques (e.g., cell culture, Western blotting, PCR/qPCR, cloning, and recombinant protein expression/purification).
• Experience with fluorescence microscopy (e.g., confocal, live‑cell imaging) or image analysis software (e.g., Fiji/Image
  
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• Advanced cell manipulation (e.g., genome editing via CRISPR/Cas9, flow cytometry/FACS).
• Basic familiarity with data analysis tools (e.g., Graph Pad Prism, R, or Python) for statistical analysis and data visualization.

• The chance to drive high‑impact research focused on addressing fundamental, mechanistic questions in autophagy and cellular homeostasis research.
• Integration into a highly stimulating, supportive, and international research group, with English as the…