Description of the PhD thesis project
In our group we work at the intersection of
immunology and developmental biology.
Our primary goal is to understand how
environmental cues interact with host genetic networks to regulate organ
development and physiology. We focus particularly on the intestine, which
initially forms without major influence of extrinsic factors but later develops
in interaction with several commensal microorganisms and dietary nutrients.
We study how the crosstalk between the immune
system and environmental signals regulates gut development and epithelial
function. To study these questions, we exploit the advantages of the zebrafish
model such as ex utero and rapid development, transparency, large progeny, and
simple genetic and environmental manipulation. We combine live imaging, flow
cytometry, and bulk and single-cell transcriptomics with models that induce
mucosal stress, including pathogenic challenges.
Project abstract: cytokines are small secreted
proteins originally characterized as leukocyte-derived modulators of defense
We have recently found that gut epithelial
cells of the zebrafish larva express several cytokines before
cytokine-expressing lymphocytes develop and populate this organ. These
cytokines were thought to be produced only by leukocytes and we found that
disruption of their signaling results in a profound impairment of gut
development. We hypothesize that the orchestrated action of cytokines in the
gut is essential for its development and the establishment of a functional
We propose a research project aiming to
uncover how cytokine signaling controls intestinal development and homeostasis.
Also, we aim to determine the relationship between the microbiota and cytokine
function in the control of intestinal development and physiology.
This project will provide fundamental insights
into how intercellular communication mediated by immune signals controls
organogenesis and maintains tissue homeostasis.
International, interdisciplinary &
intersectoral aspects of the project
We will exploit and strengthen our ongoing
local and international collaborations: Jean-Pierre Levraud, Institute of
Neuroscience, Paris-Saclay, France (zebrafish immunity); Jean-Marc Ghigo,
Institut Pasteur, Paris, France (gut microbiota); Carmen Feijoo, Andres Bello
University, Santiago, Chile (diet-induced gut inflammation in zebrafish);
Eduardo Villablanca, Karolinska Institutet, Sweden (mouse and zebrafish gut
The student will have the opportunity to do
research stays in these laboratories. Also, the fish lines that will be
generated will be used for high-throughput screening of molecules modulating
gut inflammation (with E. Villablanca).
Finally, this project combines conceptual and
technical approaches used in developmental biology, immunology, and
1. Coronado M, Solis CJ, HERNANDEZ PP* and Feijoo CG. Soybean Meal-Induced Intestinal
Inflammation in Zebrafish Is T Cell-Dependent and Has a Th17 Cytokine Profile.
Front Immunol. 2019 Apr 2; 10:610. doi: 10.3389/fimmu.2019.00610. PMID:
31001250; PMCID: PMC6454071. (*) Corresponding author
2. Gronke K*, HERNANDEZ PP*, Zimmermann J, Klose C, Kofoed-Branzk M,
Guendel-Rojas F, Witkowski M, Tizian C, Amann L, Schumacher F, Glatt H,
Triantafyllopoulou A, and Diefenbach A. Interleukin-22 protects intestinal stem
cells against genotoxic stress. Nature. 2019 Feb; 566(7743):249-253. doi:
10.1038/s41586-019-0899-7. Epub 2019 Jan 30. PMID: 30700914; PMCID: PMC6420091.
(*) Equal contribution.
PP*, Strzelecka P, Athanasiadis E, Hall D, Robalo AF, Collins AM, Boudinot
P, Levraud* JP, Cvejic* A. Single-cell transcriptional analysis reveals
ILC-like cells in zebrafish. Sci Immunol. 2018 Nov 16; 3(29):eaau5265. doi:
10.1126/sciimmunol.aau5265. PMID: 30446505; PMCID: PMC6258902 (*) Corresponding
PP, Mahlakoiv T, Nguyen N, Guendel F, Ryffel B, Hoelscher C, Dumoutier L,
Renauld JC, Staeheli P and Diefenbach A. Interferon-λ and interleukin 22 act
synergistically for the induction of interferon-stimulated genes and control of
rotavirus infection. Nat Immunol. 2015 Jul; 16(7):698-707. doi:
10.1038/ni.3180. Epub 2015 May 25. PMID: 26006013; PMCID: PMC4589158. Featured
Paper of the Month of July, 2015 by the Society for Mucosal Immunology.
Research highlight in Nature Reviews Immunology, 15, 402–403 (2015)
5. Mahlakoiv T*, HERNANDEZ PP*, Diefenbach A and Staeheli P. Leukocyte-derived
IFN-a/b and epithelial IFN-l constitute a compartmentalized mucosal defense
system that restricts enteric virus infections. PLoS Pathog. 2015 Apr 7; 11(4):e1004782.
doi: 10.1371/journal.ppat.1004782. PMID: 25849543; PMCID: PMC4388470.. (*)
Equal contribution. Recommended in The F1000Prime Faculty