Ruprecht-Karls-Universität Heidelberg
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Przyborski0218 - Scientist (f/m) / PhD position
Project no:
Przyborski0218

Project leader:

Project supervisor:
Przyborski, Jude
Application deadline:
31. Jan 2019
Start of PhD project:

Project description:

Title:
Atypical protein transport in malaria-infected erythrocytes: How does a membrane protein “jump” across membranes?
Summary:
Malaria is still one of the most important infectious diseases infecting humans, and kills about 400, 000 people annually. For this reason, it is essential to understand more about the cell and molecular biology of this parasite. Earlier studies on the basic cell biology of this parasite have revealed a multitude of novel phenomenon, including many related to how the parasite traffics proteins to various structures (Przyborski et al, 2016). This project aims to address one particular phenomenon, the transport of proteins beyond your boundary of the parasite’s plasma membrane. A previous study from our lab has uncovered an unusual pathway for trafficking of parasite proteins in this way, and this current project aims to build on our experience and further understand this process (Tribensky et al, 2017).
The human malaria parasite P. falciparum invades and propagates within mature red bloods cells. During invasion, the parasite envelops itself within a so-called parasitophorous vacuolar membrane (PVM), which acts as an interface between parasite and host cell, and is implicated in a number of processes important for parasite propagation. To this end, the parasite synthesises a number of proteins which intercalate into the PVM and are essential for parasite survival. However, it is so far unclear how exactly these proteins are both trafficked and sorted from the parasite to the PVM. In this project, using a number of complementary techniques, we aim to address this question and elucidate both the signals and mechanisms utilised to enable protein transport to the PVM. As a model protein, we shall firstly dissect the sorting signals and mechanisms required for the transport of the Exported Protein 1 to the PVM. Principles uncovered during this initial study will then be used to study the trafficking of further PVM-resident proteins such as members of the ETRAMP family. As protein transport to the PVM is a process underlying intra-erythrocytic development of the parasite and the subsequent pathology in the human host, any novel pathways may prove to be a chink in the parasite’s armour which may later be targeted for development of anti-parasitic drugs.
References:
Przyborski, J.M., Nyboer, B. & Lanzer, M. (2016) Ticket to ride: export of proteins to the Plasmodium falciparum-infected erythrocyte. Mol Microbiol, 101, 1-11.

Tribensky, A., Graf, A.W., Diehl, M., Fleck, W. & Przyborski, J.M. (2016) Trafficking of PfExp1 to the parasitophorous vacuolar membrane of Plasmodium falciparum is independent of protein folding and the PTEX translocon. Cell Microbiol, 19
Methods that will be used:
Molecular biology, protein biochemistry, proteomics, cell culture, transfection, cell-based assays.
Cooperation partners:
Matthias Mayer (ZMBH)
Personal qualifications:
Candidates should have a masters degree in molecular cell biology, biochemistry or equivalent disciplines. Experience with cell culture, protein biochemistry and proteomics would be an advantage. In addition, excellent knowledge in English (speaking, reading, writing) is required. The candidate should be able to independently solve problems and have a willingness to learn new techniques, including culture and transfection of malaria parasites, cell-based assays and protein purification.
Keywords:
Malaria, protein transport, erythrocytes, membrane transport