Ruprecht-Karls-Universit├Ąt Heidelberg
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Przyborski0118 - Scientist (f/m) / PhD position
Project no:
Przyborski0118

Project leader:

Project supervisor:
Przyborski, Jude
Application deadline:
31. Aug 2018
Start of PhD project:
1. Sep 2018

Project description:

Title:
The role of human proteins in export of malaria proteins to the human host cell
Summary:
P. falciparum, the aetiological agent of malaria tropica, invades and reproduces within mature human red blood cells. Having invaded the red blood cell, the parasite begins to renovate the erythrocyte to ensure its own survival, changing both the biochemical and biophysical properties of the host cell. Host cell modification is essential for parasite survival both in cell culture and in vivo (Hiller et al., 2004; Marti et al., 2004; Maier et al., 2008; Maier et al., 2009). However, such modifications are also responsible for much of the pathology associated with malaria infection. For example, parasite-modified erythrocytes display unusual adhesive phenotypes, allowing them to bind to various receptors on endothelial cells. This in turn leads to a reduction of blood flow and thus hypoxia in various organs. This so-called cytoadherance phenotype is largely responsible for pathology in the infected human host (Miller et al., 2002).
In recent years it has become clear that parasite-encoded proteins are involved in the process of host-cell modification. Conservative estimates suggest that over 250 such proteins are trafficked to the host cell, with more being identified every year (Hiller et al., 2004; Marti et al., 2004; Maier et al., 2008; Maier et al., 2009). Due to the unusual nature of this protein trafficking system, it has attracted much research interest in the past decade [reviewed in: Przyborski et al., 2016)]. However, despite growing evidence that human factors may also be involved in this process, no study has analysed this possibility in detail.
This project aims to identify human proteins playing a role in the protein export process.
References:
Hiller, N.L., Bhattacharjee, S., van Ooij, C., Liolios, K., Harrison, T., Lopez-Estrano, C. & Haldar, K. (2004) A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science, 306, 1934-1937.

Maier, A.G., Cooke, B.M., Cowman, A.F. & Tilley, L. (2009) Malaria parasite proteins that remodel the host erythrocyte. Nat Rev Microbiol, 7, 341-354.

Marti, M., Good, R.T., Rug, M., Knuepfer, E. & Cowman, A.F. (2004) Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science, 306, 1930-1933.

Miller, L.H., Baruch, D.I., Marsh, K. & Doumbo, O.K. (2002) The pathogenic basis of malaria. Nature, 415, 673-679.

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.
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, chaperones, erythrocytes