PhD PROPOSALS FOR THE
PASTEUR - PARIS UNIVERSITY INTERNATIONAL DOCTORAL PROGRAM
Time for applicants to contact host laboratories: September 14 – November 6, 2015
Deadline for full application: November 20, 2015
Interviews: February 9-12, 2016
Start of the Ph.D.: October 3, 2016
Title of the PhD project: Analysis of commensal fungi and parasites into feces of
healthy individuals: influence of travels and nutrition habits on eukaryome diversity,
and impact on the immune system
Keywords: mycobiome, eukaryome, fungi, parasites, commensals, nutrition, immunity
Department: Mycology
Name of the lab: Molecular mycology unit
Head of the lab: Françoise Dromer
PhD advisor: Alexandre Alanio/Stéphane Bretagne
Email address: [email protected]
Web site address of the lab: www.pasteur.fr/research/molecularmycology
Doctoral school affiliation and University: University Paris VII, Doctoral school BioSPC
department Infectiologie Microbiologie.
Presentation of the laboratory and its research topics:
How fungi can be a threat to human health and how to improve diagnosis and prognosis of
invasive fungal infections? Our mutidisciplinary approach relies on improving knowledge on
the pathophysiology of these infections through experimental models and translational
research, and by developing new tools for the diagnostic and the characterization of the
isolates. We use the diversity of clinical isolates and the data collected through the French
National Reference Center for Invasive Mycoses and Antifungals as a mean to assess the
clinical relevance of our experimental findings.
Part of the lab is interested in dormancy and metabolism in Fungi, in particular in
Cryptococcus neoformans and in pathophysiology of invasive fungal infections. The aim is to
bridge medical mycology with basic research on the pathophysiology of invasive fungal
infections and translating new biological tools (bench) into diagnostic test for fungal and
parasitic infections (bedside).
Description of the project:
(1 page, Arial font size 11: 600 words in total with at least 50% dedicated specifically to the
proposed PhD project(s))
Microbial communities play a positive role in human health, as demonstrated by recent
studies on archaea and bacteria (i.e. microbiome)1. However, very little is known about the
impact of eukaryome2, i.e. fungi (mycobiome) and parasites on human immunity3, although
they have been demonstrated as commensal4.
Our current project proposes to provide cartography of fungi and parasites present in the
feces of healthy individuals, and to evaluate their relation to nutrition, travel history and/or
genetic factors, and their impact on the shaping of innate and adaptive immunity.
Fungal diversity will be determined using amplicon-based metagenomic or
metatranscriptomic analysis using two universal barcode target genes5. For parasites, due to
high genetic distance between the interested organisms, we will use real-time qPCR
targeting up to 12 species or genera belonging to the six predominant groups of commensal
parasitic eukaryotes (Amoebozoa, Metamonads, Apicomplexa, Microsporidia, Stramenopiles,
Soil-transmitted helminthes)6. A high throughput approach based on the Biomark technology
(Fluidigm®) will be implemented.
Based on these techniques, we will first provide a detailed map of the diversity of fungi and
eukaryotes in healthy feces. We will then cross our datas with (i) informations on food diet of
the donors - as generated from Nutrinet substudy, (ii) travel and antibiotic consumption
history, and (iii) genetics, to evaluate the contribution of genetic and environmental
parameters to the observed phenotype. Finally, we will evaluate the impact of these
organisms and their diversity on immunity parameters, with the idea that different eukaryome
might contribute to the observed diversity of immune responses.
References:
1.
2.
3.
4.
5.
6.
Claesson, M. J. et al. Gut microbiota composition correlates with diet and health in the
elderly. Nature 488, 178–184 (2012).
Lukeš, J., Stensvold, C. R., Jirků-Pomajbíková, K. & Wegener Parfrey, L. Are Human
Intestinal Eukaryotes Beneficial or Commensals? PLoS Pathog 11, e1005039–6 (2015).
Iliev, I. D. et al. Interactions between commensal fungi and the C-type lectin receptor
Dectin-1 influence colitis. Science 336, 1314–1317 (2012).
Iliev, I. D. & Underhill, D. M. Striking a balance: fungal commensalism versus
pathogenesis. Curr Opin Microbiol 16, 366–373 (2013).
Schoch, C. L. et al. Nuclear ribosomal internal transcribed spacer (ITS) region as a
universal DNA barcode marker for Fungi. Proc Natl Acad Sci USA 109, 6241–6246
(2012).
Verweij, J. J. & Stensvold, C. R. Molecular testing for clinical diagnosis and
epidemiological investigations of intestinal parasitic infections. Clin Microbiol Rev 27,
371–418 (2014).
Expected profile of the candidate (optional):
Skills : Molecular Biology, PCR, Bioinformatics
Contact:
[email protected]