MSCA Doctoral Network PhD position: Elucidating impact of β-catenin inhibitors normal haematopoietic

Organisation/Company University of Sussex Research Field Chemistry » Biochemistry Researcher Profile First Stage Researcher (R1) Positions PhD Positions Final date to receive applications 31 Oct 2026 - 23:59 (Europe/Vienna) Country United Kingdom Type of Contract Temporary Job Status Full-time Hours Per Week 40 Offer Starting Date 1 Jan 2027 Is the job funded through the EU Research Framework Programme? Horizon Europe - MSCA Marie Curie Grant Agreement Number  Is the Job related to staff position within a Research Infrastructure?

Yes

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.

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,…