Neutrophils meet auto-antibodies: a joint PhD challenge

at  Amsterdam UMC

ABOUT THE PROJECT

Rheumatoid arthritis (RA) is a chronic disabling autoimmune disease with an unknown aetiology. The van Egmond and van Baarsen labs both work on unique research angles to better understand the pathophysiology of RA, which now come together in this project.
The van Baarsen lab is the only group in the world where lymph node (LN) biopsies from healthy individuals and patients with or at risk of inflammatory arthritis (IA) are collected and studied. They observed a high number of infiltrating neutrophils in lymph nodes of patients diagnosed with RA.
The van Egmond lab investigates the activation of neutrophils by (auto-)antibodies, and demonstrated that particularly antibodies of the IgA isotype potently activate neutrophils, and induce neutrophil migration. The finding that the presence of IgA autoantibodies predates clinical onset of disease has sparked interest for IgA in the rheumatology research field. Van Baarsen and van Egmond now join forces to investigate the hypothesis that IgA autoantibodies induce the recruitment of neutrophils into the lymph nodes of RA patients, which subsequently steers adaptive immune responses.
Both labs have complementarity tools to tackle this novel hypothesis. The van Baarsen lab has access to unique human samples, and the van Egmond lab recently created novel mouse models. By studying tissue samples from both early stage RA patients as well as (IgA)- autoantibody positive individuals at risk of disease, and through the use of novel and unique technologies, including spatial transcriptomics, this project aims to obtain fundamental new insights in the function of LN neutrophils and their role in RA. Ultimately, gained knowledge may lead to novel therapeutic targets to redirect skewed autoimmune responses in RA and possibly other autoimmune diseases.
The title of the project is “Lymph node neutrophils in inflammatory arthritis: the missing link between innate and adaptive autoimmunity?”

PROFILE

We are looking for a highly motivated and enthusiastic researcher with:

• A master degree Biomedical Sciences or equivalent, with affinity for Immunology;
• Experience with cellular responses, molecular biology, and experience with animals (article 9) is preferred;
• You have a flexible, proactive team spirit but you can also work independently;
• You have excellent communications skills in English, both written and verbal.

As a PhD student on this project you will:

• Establish detailed ex vivo spatial phenotyping of neutrophils in tissue samples (lymph node and synovium) from patients with RA and investigate their relation with clinical parameters including IgA and IgG autoantibody levels;
• Determine neutrophil function and activation by patient autoantibodies;
• Determine the in vivo role of neutrophils and IgA in inflammatory arthritis;
• Work closely with our team and collaborators on this project;
• Author manuscripts submitted to high quality peer-reviewed journals resulting in a PhD thesis;
• Present your work at conferences;
• Be involved in supervising students.