Abstract: Air pollution is a critical global problem causing an eighth of all deaths in the world. Particulate matter (PM), a major component of air pollution, has the greatest impact on human health. PM exposure contributes to a range of diseases such as cancer, COPD, heart disease and stroke, and respiratory infections. Our recent studies were the first to show that as well as damaging the host, PM has a direct impact on bacteria that can cause respiratory infections. Our data show that Black Carbon (BC) exposure results in species-specific alterations in biofilm structure in both Streptococcus pneumoniae and Staphylococcus aureus, and alters bacterial colonisation in vivo. This bacterial response to BC occurs at the genetic level, altering the transcription of key genes involved in biofilm formation, colonisation and virulence. Consequently we show that bacteria are responding and adapting to exposure to air pollution, and this has an impact on how the bacteria infect the host.

Abstract:
The endometrium is of crucial importance for mammalian reproduction and undergoes dynamic reiterative tissue remodeling during the menstrual cycle. Knowledge on cellular and molecular underpinnings of the endometrium’s biological remodeling is poor, as well as on the processes that go awry in endometrium pathogenesis. Therefore, we embarked on the development of novel organoid research models for human healthy endometrium as well as a wide spectrum of endometrial diseases.

We established organoids from healthy endometrium which strongly reproduced the tissue’s epithelium phenotype. The organoids phenocopied the physiological responses to reproductive hormones thereby mimicking the menstrual cycle ‘in a dish’. Furthermore, the organoids showed long-term expansion capacity while remaining genomically, transcriptomically and functionally stable.

Long-term expandable organoids could also be established from a broad range of endometrium pathologies, ranging from endometriosis and endometrium hyperplasia to low and high grade endometrial cancer. The organoids recapitulated characteristics of the patients' disease and faithfully captured the clinical heterogeneity of the different pathologies. Moreover, endometrial disease organoids reproduced the original lesion when transplanted in vivo.

Taken together, we established new organoid models for endometrium and a wide spectrum of endometrial diseases, thereby providing powerful tools to decipher the mechanisms underlying biology and pathology of this key reproductive organ. The eventually generated organoid biobank will at the same time provide a screening platform to test (new) drugs, even in a patient-personalized manner.