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Post-Doctoral position - Generation and characterisation of Nanobodies for the treatment of the respiratory pathology in cystic fibrosis

ABG-86042 Job Confirmed
2019-06-11 Fixed-term 21 Month > €35,000 and < €45,000 annual gross
Centre d'Ingénierie des Protéines, Université de Liège
Liège - Belgium
Biochemistry
  • Biology
  • Biotechnology
Phage display, Antibody selection, mechanism of enzyme inhibition, protein-protein interaction
2019-07-31
Research and Development

Employer

The research will be essentially carried out at the Centre for Protein Engineering, a multidisciplinary institute of nearly 80 persons that has been created more than 25 years ago. It is part of the Faculty of Sciences and of the Research Unit InBioS (Integrative Biological Sciences). The Center provides multidisciplinary and complementary approaches for the analysis of structure and function relationships of proteins. Nine closely interacting research teams constitute the framework of the Centre offering cutting-edge expertise, from isolated proteins to integrated cellular networks.

We have been working on Nanobodies for more than 20 years.  We contributed to the early  characterization of the thermodynamic properties of the Nanobodies and strategies to improve these properties. We extensively used Nanobodies as structural probes to study the mechanism of amyloid fibril formation and its inhibition. In two recent projects, we aim at developing Nanobodies in the field of lungs diseases.

The work will be carried out in close collaboration with the other partners of this interuniversity project including the groups of Prof. Rita Vanbever (Université Catholique de Louvain, https://uclouvain.be/fr/node/23153), Prof. Teresinha Leal (Université Catholique de Louvain, https://uclouvain.be/fr/instituts-recherche/irec/ltap) and Prof. Serge Muyldermans (Vrije Universiteit Brussel, http://sbrc.vub.ac.be/MuyldermansLab)

Position and assignments

Cystic fibrosis (CF) is a serious genetic disorder associated with the loss of function of the protein called CFTR (Cystic Fibrosis Transmembrane Conduct Regulator). Multisystemic, CF primarily affects the respiratory system and this is associated with the great morbidity and mortality of the disease. CFTR functions as a transcellular chloride ion transporter. The CFTR defect leads to the dehydration of the airway surface and to a decreased mucociliary clearance. As consequence, the airways are obstructed by viscous secretions which are favourable to the development of infectious agents. The chronic respiratory infection results in the local recruitment of neutrophils which release elastase; the proteolytic action of this later is the main cause of destruction of lung tissues.

The objective of this project is to genearate Nanobodies inhibiting neutrophil elastase for the treatment of the respiratory pathology in cystic fibrosis.

The main tasks of the project are (i) the selection of Nanobodies by phage display from immune libraries of Nanobody genes, (ii) the production and purification of the selected Nanobodies, (iii) the evaluation of their ability to inhibit elastase in vitro and the study of the mechanism of inhibition including the determination of the structure of the complexe with the elastase, (iv) their physicochemical characterization, (v) the evaluation of their stability in vitro and (vi) the biological characterization in vivo in healthy mice (pharmacokinetic) and in mice with the respiratory pathology of the cystic fibrosis.

 

You will be in charge of the first 5 tasks. You will supervise a technician and Master students working on the project.

Geographic mobility:

National

Starting date

2018-09-01

Profile

 

- You have recently obtained a PhD in biochemistry, biophysics or related fields.

- You have demonstrable experience in phage display, molecular biology and construct design, protein expression, purification and characterization, protein-protein interactions.

- You have excellent organization, communication, writing and team skills

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