POST-DOC Nanomedecines to inhibit proteases involved in chronic inflammatory diseases - University of Liège

The Centre for Protein Engineering (www.cip.uliege.be) is a highly interdisciplinary Centre providing complementary approaches for the analysis of structure and function relationships of proteins. Ten closely interacting research teams constitute the framework of the Centre, offering cutting-edge expertise from isolated proteins to integrated cellular networks.

The NEPTUNS lab has an expertise in the generation and selection of Nano-antibodies (also referred to as VHHs or Nanobodies®) against a wide range of antigens; it has in particular developed original protocols to select VHHs inhibiting enzymes including proteases (e.g., DOI: 10.1002/pro.5227).

The CIP has developed 3 technological platforms: Protein Factory to express and purify recombinant proteins (www.proteinfactory.uliege.be), Robotein for the high throughput production and characterization of proteins (www.robotein.uliege.be) and AlpaNano for the generation and selection of Nanoantibodies  (www.alpanano.uliege.be). The equipment and expertise of the three platforms will be used for the realisation of the project.  

Chronic inflammatory diseases, including chronic pulmonary disorders such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), asthma, and bronchiectasis, as well as chronic wound-healing disorders such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers, are characterized by excessive neutrophilic inflammation. This persistent inflammatory state disrupts the normal protease–antiprotease balance within affected tissues, resulting in tissue damage, impaired mucus clearance, sustained inflammation, and defective immune responses. Consequently, the proteases involved in these pathological processes represent attractive therapeutic targets.

This project focuses on the development of nano-antibody-based therapeutic candidates targeting two major proteases associated with chronic inflammatory diseases. It is a highly interdisciplinary project that combines expertise in molecular biology, protein production, purification and characterization, protein engineering, and computational antibody design to generate innovative biologics with significant therapeutic potential. The project will be carried out in close collaboration with clinicians partners, who provide access to relevant biological samples and access to in vivo models, thereby ensuring a strong translational component and facilitating the clinical relevance of the research.

Your mission will include

• Production of the target proteases in mammalian cells

• Design and construct libraries of nano-antibodies (also referred to as VHHs) genes for phage display 
• Carry out phage display to select VHHs specific of the targets
• Produce and purify VHHs 
• Characterise the in vitro properties of the VHHs (affinity, specificity, inhibitory efficiency, stability, epitope mapping, structure of the complex VHH/protease)
• Use in silico antibody design tools to improve the stability and affinity of the VHHs.
• Investigate their inhibitory effciency in relevant biological samples and eventually test them in a in vivo murin model
• Present findings at international meetings and contribute to publications.

• A PhD in biochemistry, protein engineering, molecular biology, immunology, or related field
• Proven experience with the expression of recombinant proteins in mammalian cells
• Experience with IHC and working with mice
• Competence in computational antibody design and molecular modelling.
• Strong analytical, problem-solving, and communication skills
• A track record of publications in peer-reviewed journals is an asset.
• You must have obtained your PhD after 1 September 2022, or be expected to complete your doctoral degree by 1 December 2026
• You must not have resided or carried out your main activity (work, study, etc.) in Belgium for more than 24 months during the past 3 years.