Berlin-based Students

Jorin Diemer 

Supervisor: Prof. Dr. Dr. h.c. Edda Klipp, Humboldt-Universität zu Berlin Department of Biology

 

Modeling ion homeostasis in Plasmodium falciparum using non-equilibrium thermodynamics

 

In this project we model different aspects of interactions between Plasmodium falciparum and the infected red blood cell with a focus on lipid metabolism and ion homeostasis of the erythrocyte before and after parasite infection. Interference with lipid metabolism is known to affect viability of the malaria parasite. Consequently, the identification of new ways to intervene with the parasite's lipid metabolism could lead to new potential drug targets. After parasite infection, ion homeostasis of the red blood cell changes drastically, mainly due to novel permeability pathways emerging in the erythrocyte's membrane. Analyzing the interplay between host- and parasite-derived ion transportways will provide new insights into regulatory mechanisms of ion transport inhibitors that have recently emerged as potential antimalarial drugs.


Julie-Anne Gäbelich

Supervisor: Alyssa Ingmundson, PhD, Humboldt-Universität zu Berlin Department of Biology

 

Characterizing protein function at the parasite-host interface during both liver and blood infection stages

 

Plasmodium parasites remodel their host cells to create an environment conducive to their development. This project investigates Plasmodium proteins present in the remodeled membranes at the interface between the parasite and host in both liver and blood cells. Understanding these membrane structures and the functions of these proteins will elucidate key mechanisms by which parasites influence their host environments. The project will use genetics, biochemistry and advanced microscopy to investigate the function of membrane structures generated by Plasmodium in their liver and erythrocyte host cells.



Stephanie Henkel 

Supervisor: Prof. Dr. Frank Seeber, Robert Koch-Institut, Berlin

Project: TBA

 


Will Hirst 

Supervisor: Dr. Simone Reber, Humboldt-Universität zu Berlin IRI Life Sciences

 

Purification and characterization of Plasmodium tubulin: A novel lead to anti-malarial drug discovery

 

Microtubules play a fundamental role in mitosis, intracellular transport, and establishing the structure of eukaryotic cells, and many diseases are treated with drugs that disrupt microtubule function. Using a recently developed affinity chromatography-based method, we have for the first time purified native tubulin from Plasmodium falciparum, which will allow us to perform the microtubule reconstitution assays central to microtubule research using this protein. I aim to characterize Plasmodium microtubule biochemistry and dynamics in vitro, and to quantitatively measure the direct effects of microtubule-disruptive drugs on Plasmodium microtubules in vitro and in vivo.


Francois Korbmacher

Supervisor: Prof. Dr. Kai Matuschewski, Humboldt-Universität zu Berlin Department of Biology

 

Conserved and lineage-specific functions of Plasmodium membrane transport proteins

 

Membrane transport proteins (MTPs) transport nutrients, metabolic products and inorganic ions across biological membranes. Although they are essential for the cell physiology of Plasmodium parasites, the actual functions of many transport proteins are still insufficiently clarified. Thus, functional analyses of MTPs are of great importance, not only due to their influence on the development of drug resistances, but also as possible targets in the development of active pharmaceutical ingredients. The aim of this work is to analyse a selection of MTPs in Plasmodium and to compare their importance, conservation, occurrence and function in the life cycle of Apicomplexan species.


Kai Pohl 

Supervisor: Prof. Dr. Leif-Erik Sander Charité - Universitätsmedizin Berlin Med. Klinik m.S. Infektiologie und Pneumologie

 

Dissecting innate immune responses of dendritic cells to blood-stage and pre-blood-stage Plasmodium falciparum

 

High-throughput CRISPR/Cas9-genome engineering will be used to identify and characterize DC-Plasmodium sensing pathways, which will then be validated together with our Australian partners from the Cockburn lab. New insights may play a role in informed vaccine or adjuvant development against malaria.


Theresa Störiko 

Supervisor: Dr. Nishith Gupta, Humboldt-Universität zu Berlin, Department of Biology, Heisenberg Research Group Leader

 

An optogenetic approach to cyclic adenosine monophosphate (cAMP) signaling in Plasmodium falciparum

 

My project will employ optogenetic methods to explore cAMP signaling in Plasmodium falciparum blood stages. We will use a light-activated adenylate cyclase to induce the generation of cAMP in intracellular parasites. Transcriptomics and phosphoproteomics analyses will then allow us to identify downstream mediators of cAMP signaling.

Timon Hick 

Supervisor: Dr. Benedikt Beckmann, Humboldt-Universität zu Berlin IRI Life Sciences

 

Cross-species RNA-protein interactions in the malaria-infected cell

 

This project will address the cell-cell communication between Plasmodium falciparum-infected red blood cells (iRBCs) via exosome-like vesicles. The main focus will be on RNA-Sequencing and RNA-protein interaction studies of vesicular RNA that is secreted from iRBCs and the pathogen itself. Finally, putative interaction partners will be subjected to functional studies, as well as further in vivo and in vitro characterisation.


Julia Jäger 

Supervisor: Prof. Dr. Frank Mockenhaupt, Charité - Universitätsmedizin Berlin Institute of Tropical Medicine and International Health

 

Polymorphisms of iron regulation in susceptibility and manifestation of malaria


The project aims to find polymorphisms in genes involved in iron regulation (e.g. SLCIIA2, SLC40A1, TF, DMT1) that are abundant in populations living in malaria-endemic regions. To confirm the protective effect of the polymorphisms it will be related to the odds of various entities and syndromes of malaria. Monoclonal antibodies and siRNA techniques will be used to identify pathways involved in potentially modified recognition and activation processes. Surface variation of infected RBCs will be identified by high resolution scanning microscopy and analysis of membrane components and adhesion properties will be done in collaboration with the Maier lab. Identified relevant polymorphisms will be tested for significance by using CRISPR/Cas9-mediated genome editing technology of erythroblasts.


Parnika Mukherjee 

Supervisor: Prof. Dr. Emanuel Heitlinger, Humboldt-Universität zu Berlin & Leibniz Institute for Zoo and Wildlife Research

 

Cross-species association of genotype and transcriptome response as driver of susceptibility and virulence

 

Understanding host-pathogen interactions is key to understanding infection mechanisms.  In malaria, little is known about genes and proteins involved in these interactions. I am studying the effects of perturbations in gene regulatory networks and of correlated gene expression on infection mechanisms, first, using online databases and second, using gene expression data of mouse models.


Birte Steinhofel 

Supervisor: Prof. Dr. Christian Schmitz-Linneweber, Humboldt-Universität zu Berlin, Department of Biology

 

Analysis of heptatricopeptide repeat proteins in Toxoplasma gondii

In the course of the project a novel family of apicomplexan organellar RNA binding proteins will be studied. Initial evidence suggests that they function in RNA stabilization, processing and ribosome assembly. As a genetically tractable model for Plasmodium biology, the role of these proteins in organellar RNA metabolism will be investigated in Toxoplasma gondii using a combination of RNA biochemistry and experimental genetics.


MD-associated PhD student:

Bertram Linderkamp  

Supervisor: Prof. Dr. Leif-Erik Sander, Charité - Universitätsmedizin Berlin Med. Klinik m.S. Infektiologie und Pneumologie

Dissecting innate responses of dendritic cells to bood-stage and pre-blood-stage Plasmodium falciparum

Dendritic cell responses to Plasmodium falciparum will be characterized in various genetic backgrounds using a newly-established cell culture model-system and human primary cells. In addition to standard immunology readouts (ELISA, FACS), single-cell whole-transcriptome analysis will afford insights into heterogeneous activation profiles of DCs after plasmodium challenge.

 



Canberra-based Students


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