A5010417824- Force Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- Trypanosoma species research and implications
- Invertebrate Immune Response Mechanisms
- Biotin and Related Studies
- Lipid Membrane Structure and Behavior
- Herpesvirus Infections and Treatments
- Toxoplasma gondii Research Studies
- Malaria Research and Control
- Immune Cell Function and Interaction
- Venomous Animal Envenomation and Studies
- Cancer Research and Treatments
- Advanced Fluorescence Microscopy Techniques
- interferon and immune responses
- Vector-borne infectious diseases
- Mosquito-borne diseases and control
- Cellular transport and secretion
- Complement system in diseases
- HIV Research and Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
Heidelberg University
2017-2024
European Molecular Biology Laboratory
2024
European Molecular Biology Laboratory
2023
Heidelberg University
2020
Roche Pharma AG (Germany)
2019
Antiangiogenic and cytotoxic effects are considered the principal mechanisms of action sorafenib, a multitarget kinase inhibitor approved for treatment hepatocellular carcinoma (HCC). We report that sorafenib also acts through direct immune modulation, indispensable its antitumor activity. In vivo cell depletion experiments in two orthotopic HCC mouse models as well vitro analysis identified macrophages (MΦ) key mediators antitumoral effect demonstrate strong interdependency MΦ natural...
Profilin is an actin monomer binding protein that provides ATP-actin for incorporation into filaments. In contrast to higher eukaryotic cells with their large filamentous structures, apicomplexan parasites typically contain only short and highly dynamic microfilaments. apicomplexans, profilin appears be the main monomer-sequestering protein. Compared classical profilins, profilins additional arm-like β-hairpin motif, which we show here critically involved in binding. Through comparative...
Animal cell shape changes are controlled by the actomyosin cortex, a peripheral actin network tethered to plasma membrane membrane-to-cortex attachment (MCA) proteins. Previous studies have focused on how myosin motors or turnover can generate local deformations required for morphogenesis. However, controls nucleation remains poorly understood. By combining molecular engineering with biophysical approaches and in situ characterization of cortical architecture, we show that tethering...
Inserted (I) domains function as ligand-binding in adhesins that support cell adhesion and migration many eukaryotic phyla. These include integrin αβ heterodimers metazoans single subunit transmembrane proteins apicomplexans such TRAP Plasmodium MIC2 Toxoplasma. Here we show the I domain of is essential for sporozoite gliding motility, mosquito salivary gland invasion mouse infection. Its replacement with from Toxoplasma fully restores tissue parasite transmission, while aX human integrins...
During transmission of malaria-causing parasites from mosquito to mammal, Plasmodium sporozoites migrate at high speed within the skin access bloodstream and infect liver. This unusual gliding motility is based on retrograde flow membrane proteins highly dynamic actin filaments that provide short tracks for a myosin motor. Using laser tweezers parasite mutants, we previously suggested form macromolecular complexes with plasma membrane-spanning adhesins generate force during migration....
Transmission of the malaria parasite Plasmodium to mosquitoes necessitates gamete egress from red blood cells allow zygote formation and ookinete motility enable penetration midgut epithelium. Both processes are dependent on secretion proteins distinct sets specialized vesicles. Inhibiting some these has shown potential for blocking transmission mosquito. To identify new vaccine candidates, we aimed define microneme content ookinetes rodent model organism berghei using APEX2-mediated rapid...
Abstract Transmission of the malaria parasite Plasmodium to mosquitoes necessitates gamete egress from red blood cells allow zygote formation and ookinete motility enable penetration midgut epithelium. Both processes are dependent on secretion proteins distinct sets specialized vesicles. Inhibiting some these has shown potential for blocking transmission mosquito. To identify new vaccine candidates, we defined microneme content ookinetes rodent model organism berghei using APEX2-mediated...
SUMMARY To migrate, divide, and change shape, cells must regulate the mechanics of their periphery. The cell surface is a complex structure that consists thin, contractile cortical actin network tethered to plasma membrane by specialized membrane-to-cortex attachment (MCA) proteins. This active constantly fluctuating system maintains delicate mechanochemical state which permits spontaneous polarization shape when needed. Combining in silico , vitro vivo experiments we show how viscosity MCA...
Abstract Introduction Immunotherapy is a promising treatment strategy for hepatocellular carcinoma (HCC). A phase III trial advanced HCC shows favorable results nivolumab compared to sorafenib. In order evaluate the outcome of different therapeutic strategies, we two mouse models. The orthotopic transplanted fragment Hep-55.1c model and inducible (iAST) were extensively characterized ex vivo in response immunotherapies, clinical situation patients. Experimental Procedures Fragments tumors...
Abstract Cell-cell and cell-substrate adhesion is critical for many functions in life. In eukaryotes, I-domains mediate as divergent tissue traversal by malaria-causing Plasmodium parasites well cell migration human leucocytes. The I-domain containing protein TRAP important sporozoite motility invasion. Here we show that the of required to adhesional properties which can be partially preserved when native replaced from integrins or an apicomplexan parasite does not infect insects. By putting...