Supervisor: Dr Mirian Romitti
This PhD position is supervised by Mírian Romitti 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
Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with median survival of 3 to 5 years after diagnosis. It is characterized by declining of lung function caused by scarring and remodeling of the interstitial surrounding the alveoli. IPF phenotype involves extensive parenchymal remodeling and is mainly associated to disruption of basal (airway) and alveolar type 2 (AT2) cells regenerative potential. Interestingly, studies have associated metabolic diseases, particularly insulin resistance (IR) and diabetes type 2 (DM2) with reduced lung function, and as independent risk factors for IPF (prevalence of 10 to 42%) and associated with higher mortality. Studies have also demonstrated that precise levels of INS are essential and contribute for regeneration of dendrites, liver and bone after injury. Although the clear clinical associations, studies evaluating the impact of insulin signaling disruption on human LOs, particularly on basal and AT2 cells regeneration potential in a disease context, like IPF, are missing.
Studying mechanistic aspects of human diseases has been challenging due to the species-specificities, especially in the context of IPF disease modeling. 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 Insulin can affect the regeneration of the lung airway and alveolar cells upon fibrosis induction (Bleomycin or IL-11-induced injury) evaluating the cell states at transcriptional, morphological, and functional levels, using human lung organoids as a research model.
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.
What we expect from you
- Motivated candidate holding a Master’s degree (or graduating, maximum 3 years) 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