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This PhD project is one of the 12 work packages within a large Dutch Science Agenda consortium termed SYMPHONY comprising multiple Dutch research and academic centers (www.symphonyconsortium.nl). SYMPHONY aims to significantly improve treatment for patients with bleeding disorders. The innovations will have significant societal impact both for patient care as well as costs for society. The scientific breakthroughs will lead to a better understanding of underlying mechanisms leading to inter-individual variation in bleeding phenotype, treatment and diagnosis necessity according to severity of disease. You will be based within the iPSC facility in the Department of Hematopoiesis as well as within the SYMPHONY consortium. This department harbors several research groups that study hematopoiesis/immunology in health and disease covering most if not all hematopoietic lineages (>60 postdocs, PhD-students, technicians and group leaders).
Sanquin provides a lively, internationally oriented, scientific environment with excellent facilities. Within the iPSC facility, we reprogram somatic cells from control, genome edited and patient material using various ways to introduce the reprogramming factors (e.g. episomal, Sendai, lentiviral). Within this project we will setup iPSC disease model systems to confirm the causative genetic basis of specific platelet disorders as discovered by other WPs within the consortium. We will employ genome editing to introduce or repair the putative mutations to confirm this causality. Subsequently, we aim to unravel the mechanisms underlying these diseases. A range of standard biochemical assays depending on the mutation(s) identified, coupled with more advanced high throughout techniques (e.g. proteomics, (single cell) RNA-sequencing, ATAC-sequencing) will be employed and integrated to understand the mechanisms behind these diseases. Affected pathways will provide novel targets for therapeutic approaches. Data from this project will show if a specific novel mutation is causative, will provide clues or even solve underlying disease mechanism(s) and identifies possible therapeutic targets.
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Fixed-term contract: 4 years.
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