Supervisor: Dr. Sabine Costagliola
The Costagliola lab, at IRIBHM, ULB, Brussels, (https://costalab.ulb.ac.be/ ; https://iribhm.org/) is seeking a creative and highly motivated PhD student. This project aims to use organoid technology to explore the role of cardiac mesoderm on the thyroid specification process from foregut endoderm.
Project Background
Thyroid tissue, the site of de novo thyroid hormone biosynthesis, is derived from ventral pharyngeal endoderm and defects in morphogenesis are a predominant cause of congenital hypothyroidism (1/3000). It is remarkable that there is an increased prevalence of cardiovascular malformations in people with defects in thyroid morphogenesis. The first molecularly recognizable step of thyroid development is the specification of thyroid precursors in anterior foregut endoderm. Recent studies have identified crucial roles of FGF and BMP signaling in thyroid specification, but the interplay between signaling cues and thyroid transcription factors remained elusive. Observations made in different species consistently point to precardiac and cardiac mesoderm as a major source of FGF and BMP ligands acting on the foregut endoderm to initiate thyroid cell differentiation. In all species analyzed, the thyroid anlage is specified in the region of the foregut endoderm that is immediately adjacent to the cardiac mesoderm forming the outflow tract of the developing heart. Zebrafish studies also showed that loss of cardiac mesoderm, impaired myocardial differentiation, or perturbed positioning of cardiac mesoderm relative to the prospective thyroid field in the foregut endoderm results in aberrant thyroid development.
Our laboratory excels in the generation of thyroid organoids from both murine and human pluripotent stem cells. The objective of this study is to utilize this organoid technology to investigate the dynamic expression patterns of NKX2.1 and Pax8, the key transcription factors implicated in thyroid specification and development. Employing a strategy involving co-culturing of in vitro derived cardiac mesodermal cells with in vitro derived foregut endoderm, we aim to delineate the influence of cardiac mesoderm on promoting the emergence of a progenitor population from the foregut endoderm, subsequently differentiating into lineage-committed thyroid precursors co-expressing NKX2.1 and Pax8. At various time point, single-cell RNA sequencing (scRNAseq) and single-cell assay for transposase-accessible chromatin sequencing (scATACseq) will be performed to decipher the molecular and genomic events underlying this precisely timed process. Additionally, these analyses aim to pinpoint the sources of ligands and receptors involved in the process.
By elucidating the molecular players and the tempo of this specification process, we aim to develop a feasible protocol for the efficient generation of thyroid organoids without genetic manipulation of the cells, making them suitable for future cell therapy applications.
Benefits
As a PhD student in our team, you will benefit from expert mentorship, cutting-edge imaging and cell biology facilities and collaborate closely with experts in organoid technology. You will engage in a multidisciplinary project encompassing organoids, gene editing, imaging and transcriptomics, addressing significant questions in the fields of thyroid and developmental biology.
Key tasks and responsibilities:
- Implement new models of organoids.
- Cellular and molecular characterization of those organoids
- Conduct single-cell RNA sequencing, single-seq ATAC sequencing and transcriptomic and genomic analysis.
Qualifications:
- Master in Biology, medical biology, Bioengineering or a related field.
This project is ideal for an ambitious and enthusiastic candidate who thrives in a dynamic environment. Proficiency in scientific English—speaking, reading, and writing—is essential.
To complete your application (see documents on our website), kindly provide a cover letter detailing your research interests and career aspirations, along with an updated CV and the contact details of two or three references.
Contact: Sabine Costagliola sabine.costagliola@ulb.be