MSCA 博士生职位：阐明 β-catenin 抑制剂对正常造血发育、Wnt 信号传导及急性髓系白血病的影响

Training program to engage flexible and disordered protein targets for therapeutic development: The oncogene β-catenin as showcase University of Sussex Project Title: Elucidating the impact of β-catenin inhibitors on normal haematopoietic development, Wnt signaling and acute myeloid leukaemia

Objectives: 1. Test the impact of β-catenin inhibitors on the self-renewal and differentiation capacity of haematopoietic stem/progenitor cells (HSPC). 2. Characterize the effect of β-catenin inhibitors on Wnt signaling in haematological cells. 3. Assess efficacy of β-catenin inhibition in models of human leukaemia.

Project Overview: Wnt signaling is important for the self-renewal/differentiation capacity of HSPC, and aberrant levels, localization, and activity of the central mediator β-catenin are frequently observed in acute myeloid leukaemia (AML) where β-catenin contributes to the emergence, maintenance and drug resistance of leukaemia stem cells. Previous reports suggest only very low levels of β-catenin activity are required to sustain normal haematopoiesis, making it an attractive therapeutic target; however, efforts to pharmacologically target the molecule have had limited success. WPs 2-6 will provide novel β-catenin inhibitors which will be tested for safety and efficacy in WP7. The School of Life Sciences at UOS has existing ethical approval for the collection and storage of primary human cord blood (as a source of HSPC) and myeloid leukaemia patient samples for use in research in collaboration with the Brighton & Sussex Medical School and East Sussex NHS Trust. This study will firstly assess the safety profiles of developed β-catenin inhibitors by testing their myelotoxicity in an optimized model of in vitro HSPC culture. Furthermore, we will assess the capacity of β-catenin inhibitors to directly target Wnt signaling output in vitro through flow cytometric assessment of Wnt signaling reporter activity (BAR; β-catenin-activated-reporter) in myeloid cells. Finally, this project will adopt pre-clinical models of primary AML samples grown in co-culture systems to evaluate the capacity of novel β-catenin inhibitors to specifically eradicate AML LSC populations through tracking of well-established immunophenotypic markers. Contribution to the overall research program: Safety and efficacy testing of β-catenin inhibitors and testing in AML models.

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: Contribution to the overall research program: Safety and efficacy testing of β-catenin inhibitors and testing in AML models.

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: None

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.

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: Host: MUG; Supervisor: Prof. Tobias Madl; Length: 4 months.

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

Work location / nr job positions: 1

Work location / job organisation institute: University of Sussex

Work location / job country: United Kingdom

Hiring contact / organisation institute: University of Sussex

Hiring contact / organisation institute type: Higher Education Institute

Hiring contact / country: United Kingdom

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): 2026-10-31T22:59:00