Master thesis available in the Schiller lab @HelmholtzMunich

Supervisors

Dr. Laurens De Sadeleer (laurens.desadeleer@helmholtz-muenchen.de)

Dr. Herbert Schiller, Deputy Director Institute of Lung Health and Disease, Helmholtz Munich

Project background

Fibrogenesis after tissue injury is one of the most prevalent clinical complications and causes of death. One of the archetypal examples of a fibrotic disease is Idiopathic Pulmonary Fibrosis (IPF), a relentless fibrotic lung disease characterized by the progressive scarring of alveolar tissues with dramatic changes in epithelial, endothelial and fibroblast cell states during disease progression (1-2). The main aim of our research is to understand how these aberrant cell states are wired together into circuits and thereby influencing each other throughout disease evolution (3-5). To better understand the altered cell-cell communication inducing these disease-specific circuits, we use state-of-the art -omics technologies, innovative imaging tools and organotypic ex vivo models.

Project description

In this project, the student will apply iterative highly multiplexed immunofluorescence (6) to characterize the tissue niche of aberrant fibroblast states in lung fibrosis. Specifically, the student will stain the very same tissue iteratively with 28+ disease-relevant antibodies and determine the spatial localisation of disease-specific cell states as well as their mutual interactions throughout disease progression.

Expert training will be received on histological and immunostaining techniques as well as state-of-the-art whole-slide microscopy and bioinformatic analysis.

Tasks for the project will include:

• Optimizing new antibodies for use in multiplexed immunofluorescence
• Learning the iterative immunofluorescence technique and applying it to understand aberrant fibroblast states in human IPF tissue with different disease severity states
• Based on the stainings, defining specific fibroblast niches and cellular circuits

Project requirements

This project will suit a highly motivated student with a background in biology or similar field with an interest in imaging and computational data analysis. Familiarity with computational data analysis is desirable but not required. Experience with staining techniques is not required but will be developed during the project. There will be regular contact with supervisors but you should also be comfortable working independently. By completing this project the student will be exposed to a cutting edge experimental systems biology research group, develop a range of research and problem-solving skills and become familiar with the challenges of method development, data analysis, and biological interpretation of iterative immunofluorescence stainings.

Diversity

Women and people from other underrepresented groups are strongly encouraged to apply and we will seek to provide any support you require to complete the project.

References

1. Adams, T. S. et al. Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis. Sci Adv 6, eaba1983 (2020).
2. Habermann, A. C. et al. Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis. Sci Adv 6, eaba1972 (2020).
3. Mayr, C. H. et al. Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers. EMBO Mol. Med. 13, e12871 (2021).
4. Strunz, M. et al. Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis. Nat. Commun. 11, 3559 (2020).
5. Mayr, C. H. et al. Autocrine Sfrp1 inhibits lung fibroblast invasion during transition to injury induced myofibroblasts. bioRxiv 2022.07.11.499594 (2022) doi:10.1101/2022.07.11.499594.
6. Gut, G., Herrmann, M. D. & Pelkmans, L. Multiplexed protein maps link subcellular organization to cellular states. Science 361, (2018).