ISSUE 356
ELAN-Pilot Projects
ELAN pilot projects provide funds for junior researchers (postdocs, until the age of 39 (i.e. before the 39th birthday) at the time of application).Projects:
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Increasing survival of young cancer patients require fertility-preservation like ovarian-cryopreservation pretherapeutically with retransplantation post-therapy. However, this is not appropriate for all patients due to the risk of relapse. A promising alternative is the artificial ovary: follicles are separated from malignant cells. In the research proposed follicle survival, maturation and growth in 3D-scaffold will be observed by live cell imaging with confocal spinning disc microscopy.
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Our preliminary study demonstrated protective effects of 3-indolepropionic acid (IPA) on the severity of CIA arthritis in mice. Our project will now I) provide insight into general IPA effects on overall brain function at rest and II) use (thermal) fMRI to evaluate central nociception as a functional readout parameter for RA severity. III) We will assess whether long-term IPA treatment up to day 35 may have additional benefits on disease progression.
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Periodontitis (PA) is a highly prevalent disease that has bidirectional associations with Diabetes and Alzheimer's disease. PA is leading to irreversible destruction of tooth-surrounding tissues and tooth loss. The pathogenesis of PA is poorly understood. Aim is the analysis of possible Th17/Treg disbalance in PA, association with pro- and anti-inflammatory cytokines, and whether these alterations are local or systemic. The goal is to identify biomarkers and potential targets for immunotherapy.
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Protocols for detection of disseminated cancer cells (DCCs) in the lymph node (LN) need to be harmonized. Therefore, immunocytology vs. conventional ultrastaging will be compared and additional methods for isolation of DCCs for subsequent molecular analysis will be tested. Correlation of morphology with DCC-density and ploidy will be examined. The prognostic impact of the morphology of LN metastases will be investigated in archival cases. Further, DCCs in the neoadjuvant setting will be studied.
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Physical activity in Fontan patients has a positive effect on cardiopulmonary capacity. Peak oxygen uptake represents the most robust predictor for morbidity and mortality in these children. It can be improved through exercise. High-intensity interval training (HIIT) represents the most efficient method, but the implementation is difficult. An App-based training represents an alternative with the possibility of providing positive feedback through a Fitness tracker.
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The focus of the present project is the effect of the human T cell leukemia virus (HTLV-1) on dendritic cells (DCs) in two models. The project focuses on the transmission of HTLV-1 to DCs across an intestinal barrier, analyzing the phenotype of DCs and the mechanism of transmission. For this purpose, two models, a 2D transwell and a 3D organs-on-a-chip model will be established. Finally, both models will be compared regarding their advantages, disadvantages and differences in the DC phenotype.
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Mutations in CTBP1 cause rare neurodevelopmental syndrome HADDTS. I have shown that CTBP1 controls hippocampal energy metabolism and protects synaptic transmission from metabolic stress Notably, deletion in glia and/or neurons had distinct effects. Here, we will investigate the role of CTBP1 in neuron-glia metabolic coupling necessary for energetic and functional homeostasis in brain. The results will provide new rational basis for treatment of HADDTS.
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In breast cancer, the success of neoadjuvant chemotherapy depends on tumor-infiltrating lymphocytes and their specificity, especially against neoantigens - promising targets for immunotherapies. 3D-cell cultures offer a more realistic representation of tumor-immune cell interactions than conventional ones. The project seeks to compare 4 T-cell receptor-based immunotherapies against neoantigens in 2D- and 3D-models, aiming to identify the most promising approach for potential future treatments.
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Lipid nanocapsules, functionalized with RGD sequence to target ?V?3 integrin receptor on podocytes and loaded with therapeutic substances will be investigated as a podocyte specific therapeutic strategy. Uptake and therapeutic potential of loaded nanoparticles to rescue proteinuric phenotypes will be investigated in different zebrafish glomerular disease models. These experiments enable in vivo analysis of nanocarriers as potential cell type specific drug delivery systems.
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Indirect capping of the dental pulp is recommended in deep cavities, but there is little clinical evidence for the success of the procedure. In an innovative simulation model of the pulp-dentin-complex, the effect of different biocompatible capping materials on human pulp cells through a dentin barrier will be tested. By analyzing cell survival, gene expression, oxidative stress and cytokine production, their bioactive effects will be compared in a way that is not possible in vivo.
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The aim of the planned project is to investigate the effect of NPWT on the cell lines involved in wound healing and on the cells generally found in the skin. Keratinocytes, melanocytes, fibroblasts, endothelial cells and ADSCs will be cultivated in combination with NPWT under dynamic conditions (continuous medium flow via a peristaltic pump). Under optimal cultivation conditions, the effects of a prolonged application of negative-pressure wound therapy will be investigated.
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This project aims to develop lipid nanoparticle (LNP) vaccines for targeted delivery of HIV-1 antigens and checkpoint inhibitors (CPI) mRNA. By displaying HIV-1 antigens on the LNP surface, we seek to efficiently target and activate Env-specific B cells. Concurrent delivery of CPI mRNA into the cells is anticipated to induce local checkpoint inhibitor production, modulating immune response without systemic CPI exposure.
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Chronic stress has long-lasting effects on the hippocampal function, but it still remains unclear how. We investigate stress-induced epigenetic changes as a biological link between chronic stress and brain dysfunction. Our preliminary data has identified lamin B1 as a target of chronic stress. Lamin B1 is an epigenetic factor that maintains heterochromatin. We will investigate how chronic stress downregulates lamin B1, and how stress-induced reduction of lamin B1 affects epigenetic regulation.
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Gait impairment as a common and real-life-relevant symptom in Parkinsons disease may be objectively and quantitatively detected by digital technologies in and outside the hospital. In this project, we aim to comprehensively analyse digital mobility data gained in a large multicenter study with regard to detecting objective mobility outcomes for describing the disease course (disease progression or therapy response) in a cohort of PD patients (n=130). All datasets are available.
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HCMV glycoprotein B variants are being studied with respect to viral fusion and syncytium formation. The specific objectives are: (1) identification of polymorphisms that enhance or inhibit fusion; (2) characterization of the fusion phenotype of these viruses in different cell lines; and (3) development of a murine CMV with hyperfusogenic gB. This study aims to understand the regulation of gB fusion activity and to identify potential diagnostic markers for HCMV pathogenicity.
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Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a fatal adult-onset neurological disease caused by pathological variants in CSF1R (colony-stimulating factor-1 receptor). As microglia are primarily affected in HDLS, we developed an iPSC-derived microglia model to study CSF1R function in healthy and HDLS patient lines. Using this model, we propose to investigate novel CSF1R interactions using APEX2-based proximity labeling focusing on transcriptional regulation.
The aim of this project is to better understand the influence of T cells and the NLRP3 inflammasome in the context of multiple system atrophy (MSA). Therefore, an already established transgenic mouse model and human brain tissue from MSA patients will be used. The aim is to lay the groundwork for further projects using T cells and NLRP3 as potential pharmacological targets for MSA treatment.
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As a result of non-specific inhibition, tyrosine kinase inhibitors (TKIs) also affect bone and cartilage development. Children and adolescents therefore suffer from significant growth retardation during therapy. Alternative therapy concepts are therefore urgently needed. In the proposed project, the influences of different TKIs on bone metabolism and cartilage differentiation will be investigated.
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The application aims to investigate endometrial cancers with regard to new molecular classifications. The ENCORE project studies real-world survival based on molecular patterns, analyzes the immune environment of tumors with concurrent p53 mutations, and correlates the eosinophil to lymphocyte ratio with patient outcome. In addition, the relevance of hormone and HER2 receptors in the individual molecular subtypes is examined.
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Chondrosarcomas are malignant bone tumors, which do not respond to existing chemo- and radiotherapy. Preliminary studies could show that the the natural compound Garcinol strongly reduces proliferation and colony formation of these tumor cells. Additionally, Garcinol could re-sensitize chondrosarcoma cells to the chemotherapeutic Cisplatin. We therefore want to investigate the role of Garcinol as a new therapeutic option for chondrosarcoma.
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The project aims to explore differences in how neonatal and adult intestinal epithelial cells respond to microbial metabolites. As the first line of immune defense, epithelial cells regulate the balance between tolerance and immune responses. The impact of bacterial colonization on gut maturation is poorly understood but may shape future immune responses. This study will shed light on how early-life events influence immune development and their role in autoimmune diseases like IBD, MS, and SLE.