Study of FcRn-mediated transport of natural and designed IgG and albumin

Immunoglobulin G (IgG) has a long serum half-life of three weeks. This feature has made IgG the number one choice for antibody-based therapeutics. Interestingly, the long half-life is shared with another abundant serum protein named albumin, which is increasingly utilized in therapy. The long half-life of these two proteins has been shown to require binding to a common cell bound receptor, the neonatal Fc receptor (FcRn). FcRn binds both IgG and albumin in a strictly pH dependent manner within acidified endosomes, and protects the proteins from degradation in lysosomes by mediating recycling of the ligands back into the blood stream.

We would like to understand the mechanism by which FcRn orchestrates pH dependent cellular sorting. We have developed unique cellular assays that will be used to identify the cellular components required for efficient FcRn-mediated rescue from degradation. Further, the assays will be used to screen how engineered IgG and albumin variants are sorted. Such knowledge will guide engineering of IgG and albumin variants with improved binding and transport properties, which may translate into therapeutics.  

Methods: The student will gain experience in standard and advanced molecular techniques including sub-cloning of genes, DNA preparation, mutagenesis, cell culturing, cellular expression systems, protein purification, ELISA, Western blotting, antibody engineering and surface plasmon resonance-based determination of binding kinetics.

 

Workplace: The work will be conducted in the Laboratory of Adaptive Immunity and Homeostasis headed by Jan Terje Andersen at Oslo University Hospital. The group is associated with the group of Inger Sandlie and the Centre for Immune Regulation (CIR):

 

The scientific goal of CIR is to identify mechanisms of immune dysregulation that contribute to autoimmune and allergic disease. Three models of autoimmune and allergic disease are studied in detail to identify novel mechanisms amenable to therapeutic intervention. Applying new information, we will develop and implement innovative agents for use in therapy. This work will involve a combination of basic research, research using animal and human disease models which will be carried out by the multidisciplinary Centre. The Centre is a collaborative of seven research groups at the University of Oslo (Oddmund Bakke, Bjarne Bogen, Frode Jahnsen, Ludvig Munthe, Shuo Wang Qiao, Inger Sandlie and Ludvig Sollid). Sollid is centre leader and Sandlie deputy leader. The CIR research activity is organized across groups, into 4 work packages, and Jan Terje Andersen is one of four work package coordinators, where the focus is “Pathogenic and regulatory antibodies”. The Centre brings in leading scientists from abroad.

 

Contact information:
Jan Terje Andersen, Oslo University Hospital, Division of Diagnostics and Intervention, Department of Immunology, Oslo University Hospital Rikshospitalet PO Box 4956 Nydalen NO-0424 Oslo, Norway. Tel: +47 95159223 E-mail: j.t.andersen@medisin.uio.no

 

Supervisors:

Inger Sandlie, Algirdas Grevys and Jan Terje Andersen

 

Published Mar. 22, 2018 10:29 AM - Last modified Apr. 19, 2018 8:13 AM

Supervisor(s)

Scope (credits)

60