Ruprecht-Karls-Universität Heidelberg
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Frischknecht0120 - Scientist (f/m) / PhD position
Project no:
Frischknecht0120

Project leader:

Project supervisor:
Frischknecht, Friedrich
Application deadline:
29. Feb 2020
Start of PhD project:
1. Apr 2020

Project description:

Title:
Understanding and inhibiting transmission of malaria
Summary:
Malaria parasites are transmitted by the bite of a mosquito, that spits so-called Plasmodium sporozoites into the skin of the host. There sporozoites migrate at very high speed through the tissue and search for blood vessels that they enter. We aim at understanding how sporozoites are formed and how they migrate within the skin.

The PhD project will focus on the molecular biology of the major sporozoite surface protein, the GPI-anchored circumsporozoite protein, that also builds the basis for the first approved malaria vaccine ‘RTS,S’. We have tagged the circumsporozoite protein with GFP and will investigate how the parasites are formed and how they migrate. Together with our collaborators we will investigate the response of the parasite to exposure of tailored antibodies that are directed against the circumsporozoite protein.
References:
1. Spreng B, Fleckenstein H, Kübler P, di Biagio C, Benz M, Patra P, Schwarz US, Cyrklaff M, Frischknecht F (2019) Microtubule number and length determine cellular shape and function of Plasmodium, EMBO Journal 38:e100984.

2. Quadt KA, Streichfuss M, Moreau CA, Spatz, JP, Frischknecht F 2016. Coupling of retrograde flow to force production during malaria parasite migration. ACS Nano 10:2091-102.

3. Singer M*, Marshall J, Heiss K, Mair GR, Grimm D, Mueller AK, Frischknecht F 2015. Zinc-finger nuclease-based double strand breaks attenuate malaria parasites and reveal rare micro-homology mediated end joining. Genome Biology 16:249.

4. Münter S, Sabass B, Selhuber-Unkel C, Kudryashev M, Hegge S, Spatz JP, Engel U, Matuschewski K, Schwarz US, Frischknecht F 2009. Plasmodium sporozoite motility is modulated by the turnover of discrete adhesion sites. Cell Host & Microbe 6:551-62.

5. Amino R, Thiberge S, Martin B, Celli S, Shorte SL, Frischknecht F and Ménard R 2006. Quantitative imaging of malaria parasite transmission to the
mammalian host, Nature Medicine 12:220-4.
Methods that will be used:
fluorescent microscopy; molecular cloning; cell culture; transfection of P. berghei; genome editing; confocal microscopy; scanning electron microscopy, electron microscopy
Cooperation partners:
This is a joint project with Prof. Rogerio Amino from the Pasteur Institute; Paris.
Personal qualifications:
Qualified candidate should have a degree from an internationally accredited institution of higher education. Technical skills in molecular cloning, cell culture, fluorescent microscopy are desirable. Interest in interdisciplinary collaborations is highly desirable. Applications from all fields of natural sciences are welcome as are candidates with a migration background.
Keywords:
Plasmodium;motility; malaria; fluorescent microscopy; cytoskeleton; cell biology, immunization