Ruprecht-Karls-Universität Heidelberg
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Portugal0218 - Scientist (f/m) / PhD position
Project no:
Portugal0218

Project leader:

Project supervisor:
Portugal, Sílvia
Application deadline:
15. Jul 2018
Start of PhD project:
1. Sep 2018

Project description:

Title:
Plasmodium falciparum metabolic activity during dry season asymptomatic infections
Summary:
We have recently shown that dry season Plasmodium falciparum infections are maintained asymptomatically during the 6-month dry season in Mali, while P. falciparum-specific humoral responses decrease (Portugal, S. et al. 2017). A differential capacity of triggering host immune responses could reflect epigenetic, transcriptional, or metabolic differences between newly transmitted parasites and parasites that persist during long periods of asexual replication in blood.
Many organisms are able to survive unfavourable environments. For example, some viruses become latent and shut down replication until conditions are favourable, bacteria reduce their metabolic activity, plants enter a dormant state, some insects do diapause and few mammals hibernate.
Rain seasonality represents such a pressure to P. falciparum parasites in many parts of the world. The absence of anopheline mosquitoes during the dry season prevents transmission to the vector and asexual replication within the human host is all the parasite can do for periods as long as seven months. Our data indicates that transcripts related to different metabolism pathways to which NAD+ is essential, are differentially regulated in P. falciparum parasites that persist asymptomatically during the dry season compared to parasites that cause disease during the transmission season. Thus, we now seek to investigate in depth the metabolic regulation and function of parasites kept asymptomatically during the dry season to clarify its contribution to the longstanding low parasitaemias which associate with the mosquito-free months in Mali. Specifically, we will determine which metabolic pathways are favored by parasites during the dry season and how effectively they associate with parasite growth. We will characterize metabolites from parasite and circulating plasma of individuals carrying chronic and asymptomatic P. falciparum parasites at different time-points during the six-month dry season to establish if specific strategies are selected during this time, and at which time or growth levels a metabolic shift emerges. These results will reveal if and how Plasmodium metabolic pathway regulation benefits asymptomatic infection in the dry season, and how these changes provide cover to the immune system allowing parasitaemias to persist undetected for several months.
References:
Methods that will be used:
Lipid extraction, RNA extraction, qRT-PCR, DNA and RNAseq, biochemestry, bioinformatics, cell culture, molecular biology
Cooperation partners:
Peter Crompton (NAID, NIH), Boubacar Traore (FMPOS, ICER Mali), Manuel LLinas (Penn state University), Britta brügger (Heidelberg University)
Personal qualifications:
We are seeking an enthusiastic PhD student to join our laboratory at the Parasitology Department of Heidelberg University Hospital.

- Graduate or Master’s Degree in Biology or related areas; work practice in Plasmodium infection is desirable; as well as experience/knowledge of cell culture, biochemestry, q-RT PCR, bioinformatics and statistics

- Excellent knowledge of spoken and written English and excellent communication skills and team spirit; organizational skills and ability to keep detailed records of experiments;

- Critical mind and enthusiasm;) and ability to work in multidisciplinary and multicultural teams.
Keywords:
Plasmodium falciparum, malaria, dry season, metabolome, lipidomic