β-蛋白激酶抑制剂在结肠癌中的作用研究博士职位

Training program to engage flexible and disordered protein targets for therapeutic development: The oncogene β-catenin as showcase University Medical Center Amsterdam Dr. Nicolas Leveille Objectives: 1. Evaluate the influence of β-catenin inhibitors on the Wnt pathway. 2. Assess phenotypic and transcriptional changes of β-catenin inhibitors in a panel of CRC cell lines. 3. Uncover β- catenin/RNA interactome changes mediated by β-catenin inhibitors.

Project Overview: Activation of β-catenin transcriptional program occurs in approximately 80% of CRC patients, which highlights the central role of Wnt signaling in CRC. Importantly, β-catenin orchestrates specific transcriptional changes through the formation of nuclear condensates, which in turn are organized by the intermolecular interactions mediated by β-catenin’s IDRs. While inhibition of β- catenin remains elusive, novel therapeutic approaches to interfere with its function are of great importance in the context of CRC. We aim to evaluate the potential influence of novel β-catenin inhibitors on the activation of Wnt signaling. Initial efforts will validate the function of these inhibitors by monitoring Wnt signaling changes through various reporter systems (e.g., TOP-Flash and TOP-GFP) and transcriptional impact on Wnt target genes. Strong inhibitors will then be studied for their phenotypic impacts (e.g., clonogenicity and proliferation) and global influence on transcription (GROseq) in CRC cell lines. We also aim to explore how these inhibitors impact β-catenin/RNA interactions and how this might tie to the formation of condensates. Functional assessment of β-catenin inhibitors will include β-catenin binders developed in WP2 and WP5. Molecules with strong inhibitory functions can be used to identify key features and improve the design of new β-catenin binders. This project has potential to discover novel β-catenin inhibitors with translational potential in CRC, as well as in other cancer types.

Contribution to the overall research program: Functional readout of the effect of designed β-catenin inhibitors on Wnt-signalling.

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: Purpose: MS analysis of response to β-catenin interactome modulation.

Requirements / required languages / language: ENGLISH

Requirements / required languages / language level: Excellent

Research experience / main research field: Chemistry

Research experience / years of research experience: None

Additional information / selection process: Applications are exclusively accepted through the Recruitment Portal (https://phdrecruiting.medunigraz.at/). The required information is specified in the recruitment portal and comprises: • Motivation statement for selected DC projects • Detailed CV; publication list if applicable • BSc/MSc diplomas and academic transcripts/supplements • Contact details for two referees

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.

Additional information / comment: Salary: The position is funded by the Horizon Europe MSCA-DN project FlexCAT (Grant Agreement No. 101311592) for three years. The selected candidate will be offered a competitive salary comprising a Living Allowance (adjusted by the country correction coefficient), a Mobility Allowance, and, if applicable, a Family Allowance. All allowances are subject to applicable social security contributions and taxation.

Planned secondment: 1. Host: UMI; Supervisor: Prof. Tiziana Bonaldi; Length: 2 months.

Additional information / info website: https://phd-recruiting.medunigraz.at/

Work location / nr job positions: 1

Work location / job organisation institute: University Medical Center Amsterdam

Work location / job country: Netherlands

Work location / job city: Amsterdam

Hiring contact / organisation institute: University Medical Center Amsterdam

Hiring contact / organisation institute type: Higher Education Institute

Hiring contact / country: Netherlands

Hiring contact / city: Amsterdam

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

Researcher profile: First Stage Researcher (R1)

Positions: PhD Positions

Contract: Temporary

Job status: Full-time

Application deadline (as exported; timezone unverified): 2026-10-31T22:59:00