Wanted for the next possible date at the department of hematology, oncology & rheumatology at the university hospital Heidelberg and the DKFZ. We are looking for a PhD student for our project “Cellular plasticity driven by innate immune activation in DDX41-mediated myeloid malignancies”. This project is part of the SFB/CRC 1709 “Cellular Plasticity in Myeloid Malignancies: From Mechanisms to Therapies” and funded by the Deutsche Forschungsgemeinschaft. Wihtin this CRC, we will focus on new intrinsic and extrinsic factors that enable and regulate cancer cell plasticity in myeloid malignancies. Our overall goal is to pave the way for new cancer therapies. Inherited mutations in the RNA helicase DDX41 represent the most frequent genetic predisposition to myeloid neoplasms, yet the mechanisms by which they drive disease remain poorly understood. Increasing evidence suggests that both innate immune signaling and alterations in the bone marrow microenvironment critically shape leukemic transformation in these patients. The aim of this PhD position is to investigate how DDX41 mutations in mesenchymal stromal cells (MSCs) mediate inflammation, hematopoietic stem/progenitor cell plasticity (HSPCs), and leukemic transformation. The project will use innovative 2D and 3D HSPC/MSC co-culture models, functional clonogenic and differentiation assays, bulk and single-cell transcriptomics, and multiplex cytokine profiling to dissect stromal-hematopoietic interactions. In addition, the PhD student will assess the therapeutic potential of STING inhibition, alone or in combination with chemotherapy, in patient-derived and experimental model systems. To resolve clonal hierarchies and differentiation states, the project will apply CITE-seq and the CloneTracer pipeline in close collaboration with partner labs, providing a powerful framework to link genotype, phenotype, and microenvironmental context. By integrating functional and molecular analyses, this work aims to uncover microenvironmental mechanisms driving DDX41-mediated myeloid malignancies and to identify new strategies for targeted therapy. HSPC/MSC 2D and 3D co-culture experiments: differentiation and clonogenicity assays, functional perturbations, and cytokine profiling Bulk and single-cell transcriptomic analyses: RNA-seq, multiplex ELISA, integration of molecular readouts from co-culture experiments Single-cell CITE-seq and CloneTracer applications: clonal tracing, linking DDX41 genotype with differentiation state and microenvironmental context, in collaboration with CRC partners STING inhibition and drug sensitivity assays: testing effects of STING inhibitors alone and in combination with chemotherapy in patient-derived and model systems Data analysis, interpretation, and collaboration within the CRC: bioinformatics-assisted interpretation of molecular and functional data, close interaction with collaborating groups Master degree (or similar) in molecular biology, biomedicine, biotechnology, bioinformatics, or a related field Experience in molecular biology methods (e.g. PCR, NGS, cell culture) and/or functional cell assays Interest in translational leukemia research, inflammation, and innovative omics technologies Bioinformatics experience, e.g. Python Ideally initial experience with co-culture systems, cytokine profiling, or single-cell multi-omics Collectively agreed remuneratio(TV-L E13), attractive company pension scheme (VBL) 30 days vacation Sustainable travel: job ticket Family-friendly working environment: cooperative arrangements for childcare, subsidy for child vacation care, advice for employees with relatives in need of care Wide range of health, prevention and sports offers Working with the latest techniques / technical equipment single-cell sequencing, including CITE-seq and CloneTracer, advanced co-culture models Possibility of doctorate Possibility of habilitation Possibility to publish scientifically is offered and supported Regular team meetings Interdisciplinary cooperation with the department of immunology Close collaboration within a large research consortium