肽类β-蛋白酶抑制剂的细胞摄取研究博士职位

Training program to engage flexible and disordered protein targets for therapeutic development: The oncogene β-catenin as showcase Institute for Applied Synthetic Chemistry, Technical University of Vienna (TU Wien) Assist. Prof. Anne Conibear What we offer: • Funded full-time doctoral position (40 h/week for 36 months, fixed-term) within an international, application-oriented research network, with structured doctoral training and individual career development. MSCA funding covers a 36-month employment period. At host institutions where the doctoral programme is designed for four years, additional funding for a fourth year may be available through the host institution and/or the recruiting PI’s research grants. Availability, duration and conditions of such additional funding depend on the individual DC position and host institution and will be specified where applicable. • Remuneration package provided according to the MSCA Doctoral Network rules (adjusted per country correction factor). Mobility allowance and family allowance (if eligible). • As part of the FlexCAT-DN, you will participate in several international doctoral training programs (~ 3 weeks over 3 years) at different European locations, as well as at least one secondment to an international academic or industry partner. • An interdisciplinary supervisory team and an individual career development plan. Transferable skills courses and networking opportunities. • Opportunities to present your research at international conferences and to engage in scientific dissemination, communication, outreach and, where relevant, exploitation and innovation activities. Project Title: Cellular uptake of peptide-based β-catenin inhibitors Objectives: 1. Generate insight into the structure/uptake relationship for tested peptidomimetics. 2. Obtain peptidomimetics with reduced peptidic character, as well as molecular weight and increased cellular uptake.

Project Overview: This project will use already validated peptide-based β-catenin inhibitors (e.g., β- hairpin and helix-based scaffolds reported by the Grossmann lab) as the starting point. The aim is to obtain inhibitors with reduced molecular weight (MW < 1000 g/mol) and the ability to efficiently cross the cell membrane. This will require additional sequence maturation and the reduction of the peptidic character, and involve incorporation of non-natural amino acids using structure-based and computerguided approaches. We will synthesize a panel of peptidomimetics (>100, in multiple iterations) to systematically probe the effect of changes in polarity, size, and flexibility on cellular uptake. The primary readout to assess β-catenin binding is the fluorescence polarization assay which will be combined with TOPFLASH reporter gene assays using various cell lines (including various colorectal cancer cell lines, e.g., DLD1 and SW48) to assess potential cell line/type-dependent differences in uptake. Characterization will involve NMR conformational studies in the Conibear lab, MD simulations, structural modeling, and cellular uptake analysis (Madl, Pritišanac, Schueler-Furman). Computational approaches (Schueler-Furman, HUJ) will be applied on the uptake profile of tested peptidomimetics. Inhibitors with cellular activity will be tested in disease models (AMC and Genentech) and the β- catenin interactome (Bonaldi). The goal is to identify lead inhibitors that are suitable for in vivo testing (van Neerven lab).

Contribution to the overall research program: Feasibility and structure/uptake data on peptide and peptidomimetic β-catenin binders.

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: • Completion of a master or diploma curriculum in chemistry or chemical biology, or closely related field. Ability to carry out laboratory experimental work and data analysis skilfully and responsibly. • Interest in research in the field of protein chemistry: Curiosity, self-motivation, resilience, and willingness to learn. • Experience in one or more of the following scientific fields: Peptide synthesis and characterisation, NMR spectroscopy of peptides/proteins, proteomics, or mammalian cell culture. • Enthusiasm for scientific communication and public engagement. • Teamwork, innovation and problem-solving skills.

Requirements / required languages / language: ENGLISH

Requirements / required languages / language level: Excellent

Research experience / main research field: Chemistry

Research experience / years of research experience: 1 - 4

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. Key dates: • Applications open: 15 September 2026 • Applications close: 31 October 2026 • Online pre-interviews: early November 2026 • Final interviews: late November/early December 2026 • Decisions and offers: mid-December 2026 • Start: January 2027 – March 2027

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: tba; Supervisor: tba; Length: 4 months.

Purpose: Testing cellular uptake.

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

Work location / nr job positions: 1

Work location / job organisation institute: Technische Universität Wien, Institute of Applied Synthetic Chemistry

Work location / job country: Austria

Work location / job city: Wien

Work location / job postal code: 1060

Work location / job street: Getreidemarkt 9/163

Hiring contact / organisation institute: TU Wien

Hiring contact / organisation institute type: Higher Education Institute

Hiring contact / division faculty: Institute for Applied Synthetic Chemistry

Hiring contact / country: Austria

Hiring contact / city: Wien

Hiring contact / postal code: 1040

Hiring contact / street: 13 Karlsplatz

Hiring contact / website: https://www.ias.tuwien.ac.at/hm/anne-claire-conibear

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

Research field / main research field: Chemistry

Research field / sub research field: Organic 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