PhD Position – Shaping the Colorectal Niche (Sander Foundation) - (m/f/d)

Stellenbeschreibung:

Das Sind Wir

Research Group Prof. Claudia Günther (Labor für Gastrointestinale Pathophysiologie).

Join a highly collaborative and innovative research environment at the Günther Lab, where we investigate fundamental mechanisms of host–microbe interaction with direct translational relevance in human disease. Our group focuses on how the intestinal microbiota and microbial products shape epithelial, immune, and stromal responses in inflammatory and oncogenic contexts.

Colorectal cancer research is entering a transformative phase and you can be at the forefront of discovering how bacteria actively drive tumor initiation.

The intestinal microbiota is increasingly recognized as a central determinant of colorectal cancer (CRC) development and progression. Beyond compositional shifts, functional properties of specific microbial populations critically shape epithelial transformation, genomic stability, and tumor–host interactions. In particular, certain pathobionts enriched in CRC patients produce genotoxic factors that directly damage host DNA and contribute to malignant transformation.

Emerging evidence suggests that bacterial extracellular nanoparticles, including outer membrane vesicles (OMVs), represent a previously underappreciated mechanism of microbe–host communication. These nanoscale structures enable the protected transport of bioactive cargo across biological barriers, facilitating the targeted delivery of toxins and signaling molecules into host cells. By transferring genotoxic and immunomodulatory factors, bacterial vesicles may directly influence epithelial integrity, immune surveillance, and stromal remodeling — thereby actively shaping the tumor microenvironment (TME).

Within this translational IZKF-funded project, you will investigate the hypothesis that bacterial extracellular vesicles are critical drivers of CRC initiation and progression. The project integrates mechanistic cell biology, advanced vesicle characterization, and tumor immunology to dissect how microbiota-derived nanoparticles influence tumor initiation and progression. This interdisciplinary project bridges microbiome research, cancer biology, and immunology, with the long-term goal of identifying novel diagnostic markers and therapeutic targets at the interface of host–microbe interaction in colorectal cancer.

Your Tasks

Advanced Organoid Culture: You will establish, cultivate, and manipulate patient-derived colon organoids (PDCOs) and patient-derived tumor organoids (PDTOs). This includes generating specialized apical-out and apical-in organoid models to accurately mimic luminal exposure and study the effects of reverse polarity on EV uptake.
Bacterial Culture & Nanoparticle Isolation: You will work with various bacterial strains, including wild and bioengineered strains. You will be responsible for the isolation of EVs from conditioned media utilizing ultracentrifugation techniques (110.000 x g) to separate OMVs from EV-free fractions.
Nanoparticle Characterization & Molecular Assays: You will quantify and characterize genotoxic effects, such as the induction of DNA double‑strand breaks, using high‑resolution confocal immunofluorescence (e.g., γH2AX, F‑actin, and DAPI staining). Furthermore, you will biophysically characterize isolated EVs by TEM, NTA and functional assays.
Computational Analyses & Next‑Generation Sequencing: You will perform and analyze bulk RNA, single‑cell whole‑genome sequencing as well as proteomics and metabolomics. You will apply the bioinformatics pipeline, supported by machine learning algorithms.

Comments

Please send your complete application documents in one PDF (cover letter, CV, certificates, and ideally contact details of references) with the subject "IZKF PhD Nanoparticles".

Essential Experience/qualifications

Successfully completed university degree (Master's or equivalent) in Molecular Medicine, Immunology, Microbiology, Biology, Bioinformatics, Biochemistry, or a related scientific discipline.
Strong practical experience in advanced 3D cell culture techniques, ideally handling patient‑derived organoids.
Hands‑on experience in microbiology/bacterial culture and ideally biochemical techniques for vesicle/nanoparticle isolation (e.g., ultracentrifugation).
Solid background in computational biology or bioinformatics, with a strong interest in analyzing large datasets from Next‑Generation Sequencing (RNA‑seq, single‑cell WGS, metagenomics) and applying bioinformatics pipelines (e.g., machine learning algorithms).
Proficiency in molecular biology standard methods (RNA/DNA isolation, qPCR), and imaging techniques (confocal microscopy, IHC).
Excellent English communication skills, team spirit, and a structured, independent working style in an interdisciplinary environment.

We Offer

A 65% full‑time position compensated according to the TV‑L E13 collective agreement.
The opportunity to complete a PhD in a highly translational research project at the cutting‑edge intersection of microbiome research, oncology, and computational biology.
A well‑funded working environment with a dedicated budget for high‑tech sequencing and organoid culture, embedded within an interdisciplinary team from the Department of Medicine 1 and Molecular and Experimental Surgery.

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