Area of Knowledge: LIFE SCIENCES
Endometriosis is an inflammatory condition affecting 5-10% of menstruated women and is characterized by the presence of tissue that resembles endometrium outside the uterus. It is associated with severe pelvic pain, development of scar tissue, the formation of cysts or the appearance of nodules in various tissues. Endometriosis has as well been linked to the appearance of ovarian cancer, autoimmune disorders and infertility.
While the exact origins and underlaying mechanisms of endometriosis remain elusive, the primary hypothesis suggests that fragments of menstrual endometrial tissue, reach the peritoneal cavity through retrograde expulsion via the fallopian tubes. Once there, they adhere to and infiltrate the underlying mesothelium. Endometriosis is associated with genetic alterations that affect Wnt signaling, integrin expression, the secretion of pro-inflammatory cytokines, and the regulation of hormone metabolism.
Overall, endometriotic lesions have mainly been found on pelvic organs and tissues, but also in lung, kidney or limbs. However, the mechanisms by which these cells reach this distant location, attach, migrate, proliferate, invade and induce angiogenesis are poorly understood. This is partly due to the limitations of available complex in vivo models. In contrast, Organ-on-chip (OoC) models could offer the possibility to systematically study such intricate process in a well-controlled simplified environment.
The main objective of this PhD project is to investigate the process of adhesion and migration of endometrial tissue in a controlled in vitro OoC device. To do so, an in vitro system that simulates the in vivo tissue where endometrial adhesion occurs will be designed. Then, endometrial cells will be isolated from menstrual blood obtained from patients and integrated into the in vitro platform. This approach will enable the study of adhesion and migration characteristics in response to hormonal signaling using advanced microscopy technique.
Job position description
The student will be immersed in an interdisciplinary research environment covering bioengineering, biophysics, biology and chemistry. This PhD project will be conducted in collaboration with two research groups at IBEC: the Biomimetic Systems for Cell Engineering group (BM-IBEC) and the Bioengineering in Reproductive Health open lab (BR-IBEC). The BM-IBEC group specializes in developing and applying artificial systems that mimic tissue micro and nanofeatures for biomimetic in vitro assays. Utilizing advanced biofabrication technologies like bioprinting and novel biological tools such as organoids, the group has made significant progress in creating complex in vitro models of small intestinal epithelium and engineered cardiac tissue. The BR-IBEC group focuses on studying embryo implantation and developing diagnostic tools improving women health and fertility. To this aim, the group uses advanced imaging techniques and biofabrication technologies.
The candidate will develop tissue engineering protocols to create a biomimetic in vitro model (OoC device) that is compatible with advanced microscopy techniques to study the implantation of endometrial cells. They will use cell extraction protocols to obtain cells from patients and integrate them in the OoC device. To evaluate endometrial cell adhesion, migration, and growth they will utilize molecular biology approaches combined with microscopy imaging techniques, with subsequent data analysis utilizing image processing and quantitative methods. Furthermore, the student will have the opportunity to benefit from the wide array of scientific and soft skill training provided by IBEC. They will be exposed to a vibrant scientific culture through seminars and participation in international conferences.