Postdoc position to study the cell-cell interactions within the liver macrophage niche

Ghent VIB-UGent Center for Inflammation Research

12 Sep 2019

Ghent

VIB-UGent Center for Inflammation Research

Martin Guilliams Lab

Post-doctoral

1

About the lab

The Guilliams lab at the VIB-UGent Center for Center for Inflammation Research (IRC) focuses on the biggest macrophage population of the body: the liver resident Kupffer cells.  To unravel the role of Kupffer cells in vivo we have constructed our own DTR- and CRE-expressing knock-in mice that allow the specific depletion of Kupffer cells in vivo or the knock-down of genes of interests specifically in these cells. We hypothesize the presence of a restricted number of macrophage niches per organ (Guilliams & Scott, Nature Reviews Immunology 2017). 

Our recent work reveals that each Kupffer cell crosses the endothelial barrier to be in close contact with stellate cells and hepatocytes. Thus, the stellate cell, endothelial cell and hepatocyte compose the Kupffer cell niche. This finding incites a modular view to liver organogenesis where each module is composed of a Kupffer cell, a stellate cell, an endothelial cell and a hepatocyte. 

We are particularly interested in: (i) identifying the transcription factors that imprint the liver-specific identities in each of the liver module partners, (ii) identifying the cell-cell circuits within the liver module and (iii) unraveling the role of each module partner in the maintenance of liver homeostasis and (iv) understanding what cell-cell circuits instruct liver regeneration and the formation of novel liver modules.

To address these questions we combine unique in vivo transgenic mouse model, access to clinical human liver samples, cutting-edge single-cell technologies and state-of-the-art in silico approaches. We are partners of the Immgen Consortium (www.immgen.org) and of the Human Cell Atlas Consortium (www.humancellatlas.org).

Your project

We would like to understand the cell-cell interactions within the liver module (Kupffer cells, Endothelial cells, Stellate cells and Hepatocytes). How do these cells talk to one another? What cell-cell circuits are present in the healthy liver? Which receptors are involved and what transcription factors do these receptors induce? What functional gene modules are these transcription factors controlling? What is the homeostatic function of these cells within the liver module? Can we use the knowledge of homeostatic cell-cell circuits to boost tissue regeneration?

Profile

We are seeking highly motivated and dynamic individuals with a strong passion for macrophages and a formidable team-spirit. Previous experience in immunology, developmental biology, cellular biology, hepatology, organogenesis, single-cell technologies and/or epigenetics are strongly recommended. 

  • PhD in immunology
  • Confocal Microscopy, Flow Cytometry, Genomics skills
  • Experience with mouse models
  • Strong interest in bio-informatics

  Desirable but not required

  • Experience in epigenetics, single-cell technologies or bio-informatics.
  • Experience in cell culture systems.

We offer

  • A fantastic team with a strong can-do-attitude
  • A small and modular team where each scientist has a personal project and their own identity
  • Multiple transgenic tools to knock-down genes of interest within the liver tissue module (Kupffer cells, Endothelial cells, Stellate cells and Hepatocytes)
  • Access to a state-of-the-art Flow Cytometry and Microscopy Core Facilities.
  • Novel transcription factor tools that push the limits of what can be done with primary cells
  • Single-cell transcriptomics and CITE-seq technology with panels of 200 antibodies for human and mouse surface markers
  • A team with our own very talented bio-IT technicians and a long-standing collaboration with the Bio-IT team of Yvan Saeys.
  • Access to clinical human liver samples
  • A strong network of collaborators, including members of the Immgen Consortium and the Human Cell Atlas Consortium.
  • A competitive compensation package based on expertise and experience
  • Financial support is available for at least 3 years. All members of the lab are encouraged to obtain personal fellowships (Marie-Curie, HFSP, EMBO, or National funding organizations).
  • Starting Date: as soon as possible

How to apply?

For more information contact Martin Guilliams. Please complete the online application procedure and include a detailed CV incl. list of publications, a motivation letter and the contact information of three referees.

For more information:

  • Selected Research Articles:
  1. Bonnardel & T’Jonck et al. Stellate cells, hepatocytes and endothelial cells imprint the Kupffer cell identity on monocytes colonizing the liver macrophage niche. Immunity 2019.
  2. Scott & T’Jonck et al. ZEB2 is required to maintain the tissue-specific identities of macrophages. Immunity 2018.
  3. Scott et al. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nature Communications 2016.
  4. Sichien et al. IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively. Immunity 2016.
  5. van de Laar et al.  Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop into Functional Tissue-Resident Macrophages. Immunity 2016.
  • Selected Review Articles:
  1. Guilliams, Mildner & Yona. Developmental and Functional Heterogeneity of Monocytes. Immunity 2018.
  2. Guilliams & Scott. Does niche competition determine the origin of tissue-resident macrophages? Nature Reviews Immunology 2017.
  3. Ginhoux and Guilliams. Tissue resident macrophage ontogeny and homeostasis. Immunity 2016.
  4. Guilliams, Ginhoux, Jakubzick, Naik, Onai, Schraml, Segura, Tussiwand, Yona. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nature Reviews Immunology 2014.
  5. Guilliams, Bruhns, Saeys, Hammad and Lambrecht. The function of Fcg receptors in dendritic cells and macrophages. Nature Reviews Immunology 2014.