PhD Students



Jorin Diemer 

Main Supervisor: Prof. Dr. Dr. h.c. Edda Klipp, Humboldt-Universität zu Berlin (HU) Department of Biology; 2nd Supervisor: Prof. Kiaran Kirk (Australian National University, ANU)

 

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.


Ayman Hemasa

 

Main Supervisor: Kevin Saliba PhD (ANU); 2nd Supervisor: Prof. Dr. Frank Mockenhaupt, Charité - Universitätsmedizin Berlin Institute of Tropical Medicine and International Health

 

Riboflavin requirements and metabolism by the intraerythrocytic stage of Plasmodium falciparum.

 

The intraerythrocytic stage of the human malaria parasite Plasmodium falciparum has unique vitamin requirements. Whilst progress has been made in our understanding of the parasite’s requirement for certain vitamins (e.g. pantothenate and thiamine), very little is known about the parasite’s requirement for other vitamins and the enzyme cofactors they are metabolised into. This project will investigate the parasite’s requirement for riboflavin (vitamin B2) with a view of determining whether riboflavin metabolism can serve as an antimalarial drug target.


Merryn Fraser

 

Main Supervisor: Assoc. Prof. Dr. Alexander Maier (ANU); 2nd Supervisor: Prof. Dr. Dr. h.c. Edda Klipp (HU)

 

Plasmodium falciparum lipid metabolism as a target for malaria intervention strategies

 

The survival of P. falciparum parasites relies on the metabolism of lipids. The aim of this project is to explore methods of interfering with this metabolism to decrease either the survival or virulence of these parasites. I will investigate drugs and processes known to affect metabolism, and identify other key lipid pathways by utilising both biochemical and theoretical modelling approaches. This research provides new insights into malaria treatment and prevention strategies.


Julie-Anne Gäbelich   HU Student Rep

Main Supervisor: Alyssa Ingmundson PhD, HU Department of Biology; 2nd Supervisor: Melanie Rug PhD (ANU)

 

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 

Main Supervisor: Prof. Dr. Frank Seeber, Robert Koch-Institut, Berlin; 2nd Supervisor: Prof. Dr. Christian Schmitz-Linneweber (HU)

 

Dissecting the distinct metabolic roles of the ferredoxin redox system

 

The overall aim of this project is to analyze the role of the small apicoplast-resident protein ferredoxin (Fd) in the different metabolic pathways it has been implicated in. Fd provides electrons to several important enzymes (LipA, LytB, GcpE) via protein-protein interactions (PPI), which we want to disrupt by cyclic peptides (dissociators). Identifying these dissociators by a genetic screen in E. coli and validating their specificity by biophysical binding studies and in situ expression in the apicoplast will be one aim of this project. In addition, an inducible Fd gene knockout will be attempted in Plasmodium falciparum using a conditional chemical rescue scheme. The resulting phenotypes in these transgenic parasite lines will be determined with a focus on parasite replication and growth, morphology, and biochemical profiles (e.g. fatty acid or isoprenoid content). Since a previous report implied a role of Fd in artemisinin resistance this can be validate by complementation of the Fd knockout with a set of Fd mutants.


Will Hirst 

Supervisor: Dr. Simone Reber, HU 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

Main Supervisor: Prof. Dr. Kai Matuschewski, HU Department of Biology: 2nd Supervisor: Assoc. Prof. Dr. Alexander Maier (ANU)

 

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.


Birte Steinhofel 

Main Supervisor: Prof. Dr. Christian Schmitz-Linneweber, HU Department of Biology; 2nd Supervisor: Giel van Dooren PhD (ANU)

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.


Timon Hick 

Main Supervisor: Dr. Benedikt Beckmann, HU IRI Life Sciences; 2nd Supervisor: Melanie Rug PhD (ANU)

 

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 

Main Supervisor: Prof. Dr. Frank Mockenhaupt, Charité - Universitätsmedizin Berlin Institute of Tropical Medicine and International Health; 2nd Supervisor: Gaétan Burgio PhD (ANU)

 

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 

Main Supervisor: Prof. Dr. Emanuel Heitlinger, HU & Leibniz Institute for Zoo and Wildlife Research; 2nd Supervisor: Gaétan Burgio PhD (ANU)

 

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.


Kai Pohl    HU Student Rep

Main Supervisor: Prof. Dr. Leif-Erik Sander Charité - Universitätsmedizin Berlin Med. Klinik m.S. Infektiologie und Pneumologie; 2nd Supervisor: Assoc. Prof. Ian Cockburn (ANU)

 

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 

Main Supervisor: Dr. Nishith Gupta, HU Department of Biology, Heisenberg Research Group Leader; 2nd Supervisor: Assoc. Prof. Dr. Alexander Maier (ANU)

 

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.