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What you are going to do
Leukocyte adhesion deficiencies (LAD) are a group of rare immunodeficiency disorders affecting leukocyte trafficking. LAD-I is caused by reduced or lost expression of the leukocyte adhesion molecules comprising integrins, which are crucial adhesion receptors on immune cells, whilst LAD-III is caused by mutations within an important integrin regulator, kindlin-3. We have partnered with German, Finnish and Israelian research groups, in an EU-funded eRARE project ‘LADOMICS: Multi-omics approaches for discovery of new disease mechanisms of LAD-I and LAD-III immunodeficiencies’. Besides the identification of various mutant proteins in LAD-patients, the molecular pathways for some of the disease manifestations have remained ill-defined. We will use human cell lines engineered to carry LAD mutations as well as genetically defined well-validated mouse models of LAD-related immunodeficiencies to discover and functionally validate disease mechanisms underlying these different LAD syndromes. Our contribution to the project at Sanquin within this eRARE network is focused on induced pluripotent stem cells (iPSC) technologies with patient-derived reprogrammed stem cells. Using iPSC models to culture patient neutrophils, platelets or red cells will provide the community with model systems to study blood cell development and identify novel molecular mechanisms associated with the observed mutated protein within LAD that cannot be easily addressed otherwise. The position will be largely based at Sanquin Research. The Phagocyte lab at Sanquin has a longstanding role in deciphering pathological processes related to neutrophil/leucocyte biology and collaborates with the Dept of Hematopoiesis that studies hematopoietic stem cells, T-cell differentiation and activation, and molecular mechanisms controlling megakaryopoiesis and erythropoiesis. The research is multidisciplinary and includes molecular biology, fluorescence-based techniques, high throughput techniques (mass spectrometry, sequencing) and extensive cell culture of both adult and embryonic tissues. The institute provides a lively, internationally oriented, scientific environment with excellent facilities. We are looking for a motivated, enthusiastic and flexible PhD student who has been trained in cellular culture and molecular techniques who is willing to join our research team at Sanquin to investigate these rare syndromes with state-of-the-art technology. The aim is to gain disease-overarching insight in blood cell adhesion and motility and to develop therapeutic approaches for LAD-related diseases.
What we expect from you
Prerequisites are as follows:
What we offer you
We offer you ample opportunity for development, deepening and broadening, additional training and a place to grow! Working at AMR means working in an inspiring and professional environment where development is encouraged in every respect.
For an overview of all our other terms of employment, see www.werkenbijamc.nl/arbeidsvoorwaarden-amr.
In the current project three research groups, Prof. dr. T.W. Kuijpers (Dept. of Pediatric immunology, Rheumatology & Infectious Diseases), Dr R van Bruggen (Dept of Blood Cell Research, SANQUIN) and Dr E van den Akker (Dept of Hematopoiese, SANQUIN) will join forces. The complementary knowledge and technologies of this project team will create a unique scientific environment and strong research base for the PhD student. Within the Dept. of Blood Cell Research both fundamental and clinical research is performed with a focus on immunity during infections, inflammatory disorders and neutrophil and macrophage development. The clinical background at Amsterdam UMC, location AMC Dept. of Pediatric Immunology, Rheumatology and Infectious Disease will result in a high degree of synergy for innovative translational research.
Academic Medical Center (AMC)
Meibergdreef 9, 1105 AZ, Amsterdam