MSCA 博士生职位：结直肠癌起始与发展模型中的 β-catenin 抑制研究

Princess Maxima Center, Utrecht, NL Project Title: β-catenin inhibition in models of colorectal cancer initiation and development Objectives: 1. Test the efficacy and selectivity of β-catenin inhibitors on normal and cancerous cells using in vitro cultures (cell lines/organoids) and in vivo (mouse) models. 2. Use genomic and transcriptomic profiling to identify which cancers or cancer subtypes respond best to β-catenin inhibition, providing a basis for patient stratification. Project Overview: Mutations in Wnt pathway genes that lead to constitutive activation of Wnt signalling are among the most common cancer drivers across epithelial tissues, including the colon, stomach, pancreas, skin, liver, and endometrium. Wnt signalling is a highly conserved pathway that governs tissue development, stem cell maintenance, and homeostasis throughout life, from embryonic patterning to adult tissue renewal, making its dysregulation relevant to both paediatric and adult cancers. Due to the dependency of normal epithelial cells and tissues on Wnt signalling for homeostasis, no Wnt inhibitors are currently used in the clinic. Developing compounds that inhibit β-catenin specifically in cancer cells while sparing normal tissue is therefore essential to finally make Wnt-driven cancers druggable. Novel β-catenin inhibitors designed and synthesised by consortium partners will be functionally tested in this project. Our team will establish and characterise in vitro cell lines, organoids and/or epithelioid (co-)cultures from normal and cancerous mouse and human epithelial tissue across multiple organs. In addition, we will use lineage tracing, in vivo tumour models, and spatial imaging approaches to evaluate compound delivery, efficacy, and selectivity. Genomic and (single-cell) transcriptomic profiling of treated cultures and tumours will be used to define which cancers or cancer subtypes respond best to β-catenin inhibition. From this, the project aims to develop a molecular signature that can stratify patients by likely treatment response, laying the groundwork for rational, biomarker-guided treatment strategies. Cancer cell lines and mouse models are available in the lab, and this project will be performed in close collaboration with clinical partners, ensuring access to patient material. Contribution to the overall research program: This PhD project forms the functional testing arm (WP7) of the consortium, evaluating the delivery, efficacy, and selectivity of compounds designed and synthesized in WPs 2–6. The student's findings will directly inform which candidates progress within the network and provide the biological rationale for patient stratification, with direct input from clinical partners connecting this work to patient-relevant, translational context. Skills and research profile: We are looking for a highly motivated candidate with a master’s degree in biomedical sciences, molecular biology, cell biology, oncology, or a related field. The ideal candidate has hands-on experience with mammalian cell and organoid culture, along with basic molecular biology skills such as cloning, PCR, and Western blotting. Prior exposure to cancer biology or stem cell biology is preferred, and applicants are encouraged to highlight such experience in their application. Experience with mouse work, lineage tracing, fluorescence or confocal microscopy, or single-cell transcriptomic methods is a strong plus. Beyond technical background, we are looking for someone with strong analytical and problem-solving skills, a genuine interest in translating in vitro findings toward in vivo and clinically relevant contexts, and the curiosity to engage with an interdisciplinary, technique-diverse project. Good written and spoken English is required, and the candidate should be comfortable working both independently and collaboratively within an international, multidisciplinary consortium that spans multiple countries and institutions. Salary: Gross monthly salary €3.813-€4.148 (based on a 36-hour work week). Planned secondment: Host: ULX; Supervisor: Prof. Daniel Abankwa; Length: 3 months. Purpose: BRET assay of β-catenin interactions in relevant human cancer cell models. Enrolment in Doctoral degree(s): UUT (Prof. Dr. Leendert Looijenga)

Requirements / required education level / degree: Master Degree or equivalent

Requirements / required education level / discipline: Chemistry

Requirements / skills: Applicants of any nationality are welcome to apply. To be eligible for recruitment as an MSCA Doctoral Candidate, applicants must fulfil the following criteria at the date of recruitment:

• Education – you do not hold a doctoral degree and hold (or will shortly complete) a science Master’s degree (see individual project requirements), with excellent results, qualifying you for admission to the doctoral program of the respective host institution. The successful candidate must fulfil the admission requirements of the respective doctoral programme and will be enrolled in a doctoral programme during the project.

• Mobility - you must not have resided or carried out your main activity (work, studies, etc.) in recruiting beneficiary’s country for more than 12 months during the 36 months before your recruitment. Compulsory national service, holidays/short stays and time spent obtaining refugee status under the Geneva Convention4 are not considered for this purpose.

• Language & communication – excellent command of spoken and written English (min. B2 level). Ability to communicate results clearly to diverse audiences, both in writing and verbally.

• Motivation – motivation for multidisciplinary, international doctoral research, hands-on experimental work, mandatory academic/industy secondment(s), to publish research findings in international journals, present results at conferences and contribute to project deliverables. Willingness to contribute to project network-wide activities, communication, training events, and dissemination efforts.

• Technical skills – specific to the individual DC project (see individual project descriptions).

Requirements / specific requirements: Skills and research profile: We are looking for a highly motivated candidate with a master’s degree in biomedical sciences, molecular biology, cell biology, oncology, or a related field. The ideal candidate has hands-on experience with mammalian cell and organoid culture, along with basic molecular biology skills such as cloning, PCR, and Western blotting. Prior exposure to cancer biology or stem cell biology is preferred, and applicants are encouraged to highlight such experience in their application. Experience with mouse work, lineage tracing, fluorescence or confocal microscopy, or single-cell transcriptomic methods is a strong plus. Beyond technical background, we are looking for someone with strong analytical and problem-solving skills, a genuine interest in translating in vitro findings toward in vivo and clinically relevant contexts, and the curiosity to engage with an interdisciplinary, technique-diverse project. Good written and spoken English is required, and the candidate should be comfortable working both independently and collaboratively within an international, multidisciplinary consortium that spans multiple countries and institutions.

Requirements / required languages / language: ENGLISH

Requirements / required languages / language level: Excellent

Research experience / main research field: Chemistry

Research experience / research sub field: Biochemistry

Research experience / years of research experience: 1 - 4

Additional information / selection process: Applications will be assessed for eligibility and scientific/academic quality. Shortlisted applicants will be invited to interview. The final selection will follow the open, transparent and merit-based recruitment principles of MSCA.

Work location / nr job positions: 1

Work location / job organisation institute: Princess Maxima Center

Work location / job country: Netherlands

Work location / job city: Utrecht

Hiring contact / organisation institute: Princess Maxima Center

Hiring contact / organisation institute type: Higher Education Institute

Hiring contact / country: Netherlands

Hiring contact / city: Utrecht

Hiring contact / website: https://phd-recruiting.medunigraz.at/

Application / how to apply: website

Application / application website: https://phd-recruiting.medunigraz.at/

EU funding / framework programme: Horizon Europe - MSCA

EU funding / cofund nr job position: 1

EU funding / sesam agreement number: 101311592

Research field / main research field: Chemistry

Research field / sub research field: Biochemistry

Researcher profile: First Stage Researcher (R1)

Positions: PhD Positions

Contract: Temporary

Job status: Full-time

Application deadline (as exported; timezone unverified): 2026-10-31T22:59:15