ESR 3: Gene expression in the HLA complex in autoimmune disease – POSITION FILLED

PhD research

Host:

Prof. dr. N. de Vries (Niek)

Dept Clinical Immunology & Rheumatology

Amsterdam Rheumatology and immunology Center (ARC)

Rheumatology & Clinical Immunology & Experimental Immunology

Location AMC | D3-220 | Meibergdreef 9 1105 AZ Amsterdam

T: +31205667765  |  E: n.devries1@amsterdamumc.nl

https://www.amc.nl/web/research-75/person-1/prof.-dr.-n.-de-vries-md-phd.htm

Duration: 48 months

Background

Genetic studies in many autoimmune disease have shown a strong association with polymorphisms in HLA class I or II molecules. These molecules continuously present peptides on the surface of antigen presenting cells, i.e. dendritic cells and B cells. T cells exert continuous surveillance of these peptides presented in the context of HLA molecules, which may result in the induction of highly specific adaptive immune responses, e.g. in autoimmunity. Thus, genetic variation in the HLA region is strongly associated with autoimmune disease, and molecules encoded in this region are likely to play a key role in the induction of the specific humoral and/or cellular autoimmunity observed in these autoimmune diseases. Despite this key role, there is a relative lack of knowledge regarding the role of surface expression of HLA alleles, and the role of splice variants in these diseases. In this project we will use state-of-the-art high-throughput sequencing approaches to study the role of gene expression and gene splicing in autoimmune disease.

Approach 

The PhD candidate will get acquainted with cell selection technologies, existing high-throughput sequencing approaches of the HLA, B cell and T cell receptor genes and existing data analysis methods to study gene expression and splicing. The technologies will be used to study allele-specific gene expression and gene splicing in different relevant cell types in health and disease. 

Our research team

Our team aims to better understand the interactions between HLA-presenting APCs, T-cells and B cells that define specificity in, and regulate the disease-associated adaptive immune responses in autoimmune disease. To this end we study unique biobanked and freshly acquired materials from blood, human lymph nodes, bone marrow and synovial tissue obtained during the pre-clinical and earliest phases of autoimmune disease, e.g. in rheumatoid arthritis and vasculitis. The goal is to improve clinical management of these diseases by developing novel biomarkers and identification of new targets for novel therapies. Our team currently consists of 5 PhD students, 1 postdoc and 2 research technicians. For more information see https://www.amc.nl/web/research-75/person-1/prof.-dr.-n.-de-vries-md-phd.htm.

The project is a close collaboration with prof. dr. Antoine van Kampen of the The Bioinformatics Laboratory. The team is embedded within the recently established Amsterdam Rheumatology and immunology Center (ARC) and the Amsterdam Infection & Immunity Institute (AI&II). We are involved in several national and international research projects, allowing excellent possibilities for collaborations with other research groups in academia as well as industry.