PROJECT INFORMATION
Host institution: KU Leuven
Country: Belgium
Supervisory team: Prof. Marianne Carlon (PhD promoter, KU Leuven), Prof. Jacob Mikkelsen (Aarhus University, Denmark), Prof. Laurens Ceulemans (KU Leuven).
PROJECT DESCRIPTON
The DC11 objectives are:
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To refine lung-targeting properties of cell-derived vesicles (CDV) to specific lung cell types (airway epithelium, endothelium, resident immune cells) by coupling of ligands (e.g. nanobodies) based on membrane proteins identified in scRNAseq datasets.
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To screen a library of lung-tropic CDVs to map delivery profiles to the different lung cells using advanced in vitro models.
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Selected delivery vehicles and gene editors will be tested for optimal delivery, editing and safety in a rodent EVLP system to gene edit relevant genes involved in ischemia reperfusion injury (IRI).
The project will involve experiments using in vitro models (cell lines, primary human lung cells, organ-on-chip, precision cut lung slices). Gene editing experiments in rodent EVLP will be done in collaboration with DC1.
A successful project will result in:
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Single cell profile of selected CDVs for their cell-specific entry and editing in primary human or rodent lung epithelial, endothelial and immune cell sub-populations.
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VLP CRISPR silencing of IRI-related target genes, validated using in vitro models and rodent EVLP.
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Thorough safety assessment of both the CDV and gene editing strategy.
Enrolment in Doctoral School: KUL Doctoral school of Biomedical Sciences, Faculty of Medicine
Planned secondments:
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Aarhus University, Denmark: intracellular determinants for efficient pulmonary gene editing (months 15-16)
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Astra Zeneca AB, Sweden: Assessment of safety of CDV-loaded gene editors on immune and genotoxicity in relevant vitro platform (months 26-30)
ESSENTIAL REQUIREMENTS
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You hold a Master’s degree (no PhD) in bioengineering, biomedical sciences, biotechnology, civil engineering, pharmacy or a related field
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You are passionate about life sciences and engineering, and want to achieve a PhD degree on the topic described in the description above
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You have prior experience, or at least a strong theoretical background, on at least some of the aspects listed above,
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You are ambitious, well organized and have excellent communication skills
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You are proficient in English both spoken and written
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You have a solutions-oriented mindset that thrives in a multidisciplinary team
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You have the ability to work independently and have a critical mindset.
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You are an enthusiastic and motivated person, eager to participate in network-wide training events, international travel and public awareness activities.
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Willingness to travel
DESIRABLE SKILLS AND EXPERTISE
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Practical expertise in CRISPR-based genome editing, including guide RNA design, off-target assessment
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Experience in gene delivery technologies, such as lentiviral vectors, AAVs, lipid nanoparticles, or extracellular vesicles and application in cell or animal models.
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Bioinformatics skills in analyzing bulk and single-cell RNA-seq data.