Effect of air pollution on developing and mature human lung organoids 

Supervisor: Dr Mirian Romitti

This PhD position is supervised by Mírian Romitti, a new young PI at IRIBHM and it is based in the IRIBHM-Jacques Dumont Institute (Faculté de Medicine) at the Université Libre de Bruxelles (ULB). The hosting institute/university is international, inclusive, and well-known for its significant contributions to basic and translational fields. The proposed topic is part of a larger project based on using stem cell-derived organoids to study human lung development and to model pulmonary diseases. The student will be part of a young and energetic team and work in close collaboration with other master’s and PhD students, as well as with a group of collaborators holding great expertise in bioengineering, bioinformatics, immunology, toxicology, and medical doctors.  

About the project 

It is well established that exposure to particle pollution is a significant threat to health at distinct stages of human life, resulting in premature birth, causing/worsening heart and lung diseases, and consequently shortening lives. In the case of the lungs, exposure to pollution impacts its growth and function, both prenatally and postnatally. In young kids, ambient pollutants increase the risk of respiratory infections, developing or worsening asthma, and chronic diseases. Recent data has demonstrated that black carbon (BC) particles can be found in fetal lungs during the first and second trimesters of pregnancy. Despite the shreds of evidence of particle accumulation in fetal and adult lungs little is known of how it can impact development and physiology.  

Studying mechanistic aspects of human diseases has been challenging due to the species-specificities and the difficulties in accessing human samples. However, organoid technology emerged as a great tool filling the gap in human research. Our lab recently generated a novel human lung organoids model derived from human stem cells (hESCs) that derives the full organ. This new system allows live tracking of the lung developmental stages and generates both the epithelial (airways and alveoli) and the stromal compartment of the organ. 

Major goal: Dissect how ambient pollutants (BCs) can affect lung development (“fetal” stages) and function (“adult”) by evaluating their deposition among the lung cells and how it can affect the cell state at transcriptional, morphological, and functional levels, using human lung organoids as a research model. 

Publications:  

H. Lasolle, A. Schiavo, A. Tourneur, P. Gillotay, B. de F. da Fonseca, L. Ceolin, O. Monestier, B. Aganahi, L. Chomette, M. M. L. Kizys, L. Haenebalcke, T. Pieters, S. Goossens, J. Haigh, V. Detours, A. L. S. Maia, S. Costagliola, and M. Romitti Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids. Oncogene 1–16 (2023) doi:10.1038/s41388-023-02889-y. 

Mírian Romitti, Barbara de Faria da Fonseca, Gilles Doumont, Pierre Gillotay, Adrien Tourneur, Sema Elif Eski, Gaetan Van Simaeys, Laura Chomette, Helene Lasolle, Olivier Monestier, Dominika Figini Kasprzyk, Vincent Detours, Sumeet Pal Singh, Serge Goldman, Samuel Refetoff, Sabine Costagliola, « Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism » Nat Commun 13, 7057 (2022).  https://doi.org/10.1038/s41467-022-34776-7 

Main techniques to be used (experience not mandatory) 

  • hESCs culture. 
  • Organoid cell culture using static and microfluidics conditions (interaction with bioengineers). 
  • Co-culture with immune cells. 
  • Single Cell Transcriptomics (including spatial scRNAseq) and Chromatin Remodeling assessments (ATACseq) (interaction and training with bioinformaticians). 
  • Immunofluorescence, Electron Microscopy, MERFISH and Flow cytometry. 
  • Live imaging and high-resolution microscopy. 
  • Black carbon detection (femtosecond pulsed illumination in collaboration with the University of Hasselt). 

What we expect from you 

  • Motivated candidate holding a Master’s degree (or graduating) in degree in medicine, biomedical sciences, pharmaceutical sciences, biology, bioengineering, biochemical sciences, or a related field.  
  • Ability to work in a team of young-friendly scientists, to be flexible, and to incorporate into a fast-paced environment.  
  • The capacity to work independently while keeping a strong team spirit. 
  • Strong self-motivation, organizational skills, and ability to lead and develop scientific projects. 
  • Good English language skills (speaking, reading, and writing) are also required. 

What you will find 

  • The PhD student will be supported by a Thesis Advisory Committee, participate in scientific and professional skills courses, and attend international conferences. 
  • Weekly, the student will participate in a lab meeting with other teams working on organoids.  
  • The Institute provides an interactive environment and the student will have the opportunity to interact with students/researchers working on many distinct fields. 
  • Since the project involves collaborations with teams inside and outside ULB, interaction with those teams will be part of the PhD training and the student will have the possibility to learn new technologies/techniques in those other laboratories. 
  • Competitive salary. 

Contact: Mírian Romitti – mirian.romitti@ulb.be 

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