Decoding the β-Catenin PTM Interactome with Quantitative Proteomics

 

Prof. Tiziana Bonaldi  •  University of Milan  UMI/SEMM  •  FlexCAT DC8

PROGRAMME
4-year PhD (SEMM)

MSCA FUNDING
36 months + 1-year PI extension

SECONDMENT
3 months • PMC

START
Jan–Mar 2027

PROJECT AT A GLANCE

β-catenin is a central signalling protein whose activity is shaped by post-translational modifications (PTMs) and interactions involving intrinsically disordered regions (IDRs). Recent evidence that PRMT2 directly methylates β-catenin, promoting its proteasomal degradation, provides a mechanistic basis to investigate how arginine methylation interacts with phosphorylation to regulate β-catenin states. This PhD will develop quantitative mass-spectrometry proteomics to connect defined PTM states with interaction-network remodelling and cellular responses. By integrating peptide-based interactomics, controlled PTM variants and perturbation-driven proteomics, the project will move beyond lists of interactors toward quantitative “PTM barcodes” that describe modification state, network configuration and downstream proteomic response.

WHAT YOU WILL INVESTIGATE

  • Develop and benchmark quantitative MS-based proteomic strategies to resolve PTM-dependent β-catenin interaction networks.
  • Determine how individual and combinatorial PTMs — including S/T phosphorylation and R methylation — rewire β-catenin/IDR interactions and propagate into cellular proteomic responses.
  • Build quantitative proteomic signatures that link defined β-catenin perturbations to interaction-network remodelling and pathway states, distinguishing direct PTM-dependent effects from secondary responses.

RESEARCH APPROACH

1  MAP

2  QUANTIFY

3  VALIDATE

Peptide-array pulldowns + quantitative MS to identify PTM-sensitive interactions.

Comparative interactomics across phosphorylation, methylation and combinatorial PTM states.

Perturb kinases/phosphatases and PRMT pathways; compare cellular proteomes with molecular PTM signatures.

AN INTERNATIONAL, INTERDISCIPLINARY PhD

The project is embedded in the FlexCAT MSCA Doctoral Network and connects complementary expertise across the consortium. The Maric lab (JMU, WP2) will support peptide-array screening and validation of β-catenin-binding IDR sequences; the Conibear lab (TUW, WP3) will provide defined phosphorylated/methylated peptides and semi-synthetic β-catenin constructs. Structural studies (Madl, MUG) and bioinformatic/network analysis (Pritišanac, HZM) will support mechanistic interpretation and prioritisation of regulatory modules.

 

 

TRAINING, CANDIDATE PROFILE & PRACTICAL INFORMATION

YOUR TRAINING & RESEARCH PROFILE

You will develop an interdisciplinary profile at the interface of quantitative proteomics, protein-interaction biology and PTM-dependent signalling, with particular emphasis on using proteomics as a hypothesis-generating and mechanistic technology.

  • Advanced quantitative MS-based proteomics and multi-condition experimental design
  • Affinity-based interactome profiling and analysis of PTM-dependent protein-interaction networks
  • Cellular perturbation experiments and integration of molecular and proteome-wide datasets
  • Quantitative signatures, regulatory-network analysis and experimentally testable pathway-state models

PLANNED SECONDMENT

HOST

SUPERVISOR

LENGTH

FOCUS

PMC

Dr. Sanne van Neerven

3 months

Cell-based validation

 

Aim: perturb β-catenin regulatory pathways and generate matched samples for quantitative proteomic profiling, enabling validation of PTM-dependent interaction signatures in a cellular context.

WHO CAN APPLY

  • You do not hold a doctoral degree and hold (or will shortly complete) a science Master’s degree with excellent results that qualifies you for admission to the host doctoral programme.
  • MSCA mobility rule: at recruitment, you must not have resided or carried out your main activity in Italy for more than 12 months in the previous 36 months (with the exceptions specified by MSCA rules).
  • Excellent spoken and written English (minimum B2) and strong motivation for independent research in an international, multidisciplinary network.
  • Motivation for hands-on experimental work, international secondment(s), publication, conference presentation, training and dissemination activities.

WHAT WE OFFER

• 4-year PhD programme through UMI/SEMM
• 36 months funded by Horizon Europe MSCA-DN FlexCAT (GA 101311592)
• 1-year extension covered by the PI to complete the SEMM PhD with salary according to SEMM program

• Competitive MSCA remuneration: Living Allowance + Mobility Allowance + Family Allowance, if applicable
• International FlexCAT training, interdisciplinary supervision, networking and conference opportunities
• Allowances subject to applicable social-security contributions and taxation

HOW TO APPLY

Applications are accepted through the MUG portal. Submit all documents as one PDF named Surname_FirstName_DCproject.pdf. For DC8, indicate that you are applying for the University of Milan/Bonaldi project.

  • Motivation statement for the DC project
  • Detailed CV; publication list if applicable
  • BSc/MSc diplomas and summaries/abstract or research in English
  • Contact details for two referees

KEY DATES

OPEN

DEADLINE

PRE-INTERVIEWS

FINAL INTERVIEWS

START

15 Sep 2026

31 Oct 2026

Early Nov 2026

Late Nov / early Dec

Jan–Mar 2027

Doctoral enrolment: UMI / SEMM  •  www.semm.it   |  FlexCAT MSCA Doctoral Network  •  Grant Agreement No. 101311592