The Laboratory of Molecular and Cellular Signaling (https://tinyurl.com/5cxcze5p), led by Prof. Geert Bultynck, and the Laboratory of Autophagy and Membrane Trafficking, led by Prof. Alex van Vliet, part of the Department of Cellular and Molecular Medicine, invites applications for a PhD candidate position. The candidate will conduct a joint PhD project investigating BCL-2 function at membrane contact sites and autophagy under the supervision of Prof. Geert Bultynck and Prof. Alex van Vliet .
Project
Anti-apoptotic BCL-2 proteins enable cell survival by preventing mitochondrial BAX/BAK-pore formation and by preventing pro-apoptotic Ca2+-release from the endoplasmic reticulum (ER) (Vogler M et al, Signal Transduct Target Ther, 2025). Hematological cancers are addicted to BCL-2 for their survival by counteracting pro-apoptotic oncogenic signaling. Hence, BCL-2 inhibitors emerged as novel precision medicines of which venetoclax is now FDA-approved for treating CLL patients. At the ER, BCL-2 proteins interact with IP3 receptor (IP3R), where they directly inhibit their Ca2+-flux properties (Cauwelier C et al, BBA-Mol Cell Res, 2024). As IP3Rs also reside at ER-mitochondrial contact sites (ERMCS), BCL-2-mediated inhibition of IP3Rs also prevents pro-apoptotic mitochondrial Ca2+ overload (Loncke J et al, BBA-Mol Cell Res, 2025). BCL-2 is thus a well-known anti-apoptotic protein, and most research has focused on this aspect of BCL-2. However, what the role of BCL-2 is in post-mitotic cells like neurons has been chronically understudied and is not well known. In this project, the Bultynck (Ca2+, IP3Rs, ERMCS, BCL-2 and autophagy expertise) and van Vliet (autophagy proteins, lipid signaling and membrane-contact sites expertise) labs with their highly complementary expertise’s will join forces to examine this important and overlooked aspect of BCL-2.
Experimental techniques include:
- Molecular and cell biology, including cloning, mammalian expression approaches, immunoblotting,
- Targeted mutagenesis and CRISPR/Cas9-mediated knockout
- Functional characterization of subcellular/organellar Ca2+ signaling in single cells and cell populations
- Analyses of organellar contact sites
- Autophagic flux analyses
- Cell death analyses including flow cytometry and automated microscopy
- Cellular imaging using fluorescence microscopy and 96-well imaging systems
- Flow cytometry
- Mammalian cell culture (cell models, including iPSC-derived cell lines)
- Integration of biochemical, cellular and chemical biology approaches
Profile
- Master’s degree in Pharmaceutical Science
- Experience in:
- Mammalian cell culture
- Fluorescence microscopy of living cells for the analysis of time-resolved calcium signaling and organellar contact sites
- Immunoblot analyses of cell samples
- Autophagy and cell death analyses
- Broader domain of neurodegenerative diseases
- Critical thinking and ability to think about experimental design, analyse data rigorously, and solve technical problems proactively.
- Rigorous, organized and proactive with a collaborative mindset and enthusiasm to work in an international and interdisciplinary environment.
- Proficiency in English, both spoken and written
Offer
- A stimulating, internationally renowned research environment at the intersection of two fundamental cell biological processes
- The opportunity to contribute to high-end research on calcium signaling, membrane contact sites, autophagy
- A close collaboration with international research consortia and funding agencies, generating extra opportunities for future career development
- Access to training and expertise for laboratory techniques
Interested?
For more information please contact Prof. dr. Geert Bultynck, mail: [email protected] or Prof. dr. Alex van Vliet, mail: [email protected].
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