PhD projects 2022
Hartmann Lab and Niesner Lab
Project Title "Locomotion of parasitic nematodes in the gut: movement in viscoelastic mucus intertwined with the metabolic activity of the nematodes (2 PhD positions: immunology/parasitology and biophysics/medical physics, respectively)"
Supervisors Prof. Susanne Hartmann and Prof. Raluca Niesner
Address Freie Universität Berlin, Institute of Immunology, Robert von Ostertag-Str. 7, 14163 Berlin and DRFZ (German Rheumatism Research Center), Charitéplatz 1, 10117 Berlin
Project Description
Gastrointestinal nematodes are globally distributed, highly prevalent parasites of humans and animals. Only marginal knowledge is available on the locomotion of worms in the gut, the energy household and defense metabolism of the parasites. In the project we will focus on the interface between parasitology and physics. The following questions will be addressed: i) how do adult worms locomote in the gut against the flow (PhD biophysics) and why do they locomote (PhD parasitology)? ii) Which roles do mucus viscosity play and do mucus properties change during infection? (PhD parasitology). Finally, iii) is nematode locomotion linked to the energy household metabolism of the worms (PhD biophysics)? In conclusion, we aim to elucidate mechanisms of nematode locomotion in the host gut and to understand the linkage to the viscoelastic properties of the gut mucus and metabolic activities of the worms. The two PhD students are expected to work in team to bring the project to success.
Hartmann Lab https://www.vetmed.fu-berlin.de/einrichtungen/institute/we06/forschung/index.html,
Niesner Lab https://www.drfz.de/forschung/pb1/ag/biophysikalische-analytik/
Siegmund and Weidinger Lab
Project Title "Deciphering the role of mesenteric fat in inflammatory bowel disease"
Research Group Siegmund/Weidinger - Intestinal Inflammation and Tumor Immunology
Supervisor Prof. Britta Siegmund and Dr. Carl Weidinger
Address Deptartment of Gastroenterology, Charité-Universitätsmedizin Berlin
Project Description
Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses and epithelial barrier dysfunction. Our group could recently demonstrate that mesenteric fat serves as a source for various adipokines and cytokines that not only control systemic immune cell composition but also regulate the homeostasis of intestinal epithelial cells during IBD development. Within the current project we want to use human- and murine model systems of lipodystrophy to decipher how the absence of fat tissue affects the differentiation and function of immune cells and how lipoathrophy affects epithelial barrier functions. Within his project a variety of different innovative techniques will be applied in patient derived samples as well as in mouse models of colitis including scRNA-sequencing, mass cytometry, metabolic flux analyses, organoid cultures and functional assays of primary T cells.
Siegmund and Weidinger Lab: https://gastro.charite.de/en/research/ag_siegmund/
Löhning Lab
Project Title "The role of purinergic receptors in antiviral T cell immunity"
Research Group AG Löhning – Experimental Immunology & Osteoarthritis Research
Supervisors Prof. Dr. rer. nat. Max Löhning, Dr. rer. nat. Tobias Brunner
Address German Rheumatism Research Center Berlin, Charitéplatz 1/ Virchowweg 12, 10117 Berlin
Project Description
In previous studies, we have shown that alarmins, which are released upon necrotic cell death, drive antiviral immune responses by orchestrating the activation, expansion, and effector differentiation of CD8+ cytotoxic T cells (CTLs)1,2 and CD4+ helper T cells3,4. Recently, the alarmin adenosine-triphosphate (ATP) has emerged as critical regulator of CTL differentiation5. Extracellular ATP can be detected by purinergic P2X receptors on T cells and binding will induce cellular Ca2+ influx, which drastically affects CTL functionality6. We have studied the expression patterns of purinergic receptors and identified a novel candidate as being selectively expressed by effector T cells in response to inflammatory signals. Using newly established transgenic mouse strains, the PhD candidate will study the T cell-intrinsic role of ATP-P2X signaling in CTL activation, expansion, and effector differentiation in vitro and during infection with lymphocytic choriomeningitis virus (LCMV) in vivo. These experiments will be complemented by state-of-the-art next generation sequencing approaches and metabolic-flux assays.
Löhning Lab https://www.drfz.de/en/forschung/pb3/ag/pitzer-labor-arthroseforschung/
Rausch Lab
Project Title "Defining the forces exerted by Giardia attachment and the consequences for the intestinal epithelial barrier"
Research Group Rodent GI infections models
Supervisor Dr. Sebastian Rausch (sebastian.rausch(at)fu-berlin.de)
Address Freie Universität Berlin, Institute of Immunology, Centre for Infection Medicine, Robert von Ostertagstr. 7-13, 14163 Berlin
Project Description
Joint project with the Labs of A. Hauser (DRFZ/Charité), K. Jacob (U Saarland), J. Guck (MPL Erlangen)
Giardia are highly motile parasites infecting the intestinal tract of vertebrates where they attach to the epithelial cell layer with a ventral adhesive disc. To date is not known whether and how intestinal epithelial and myeloid cells (IEC, MC) exposed to giardia colonization sense the forces exerted by the attached parasites and if this process affects tissue integrity, the epithelial defense program and the activity of underlying immune cells.
Aims
- Define the impact of Giardia attachment on IEC and MC in vitro
- Determine how parasite-derived forces are sensed by the cell types forming this barrier
- Define elastic properties and force transmission in intestinal explants
- Evaluate the role of mechanosensing in epithelial barrier function and parasite control in vivo
Methods
- In vitro work with giardia trophozoites and (transgenic) organoid derived monolayers
- Fluid force, Confocal Brillouin and Atomic force indentation Microscopy
- Flow cytometry