PhD (or MD-PhD) studentship
100%
DBMR
01.01.2025
The Blank Lab and Seydoux Lab are associated with the Berne University Hospital and are part of the Lung Precision Medicine Program (Head Prof. Thomas Geiser) in the Department of BioMedical Research of the University of Bern. Both labs serve as basic and translational research platforms and are involved in research activities analyzing the impact of inhaled environmental or biomedical formulations on the respiratory airways' immune responses, both in healthy individuals and in the light of different diseases affecting the lung, such as lung fibrosis, chronic obstructive pulmonary disease, asthma and cystic fibrosis. The labs are in close collaboration with the clinical Department of Pulmonary Medicine and the Kinderklinik at the Inselspital.
Micro- and nanoplastic particles (MnP) have been shown to contaminate the soil, water and air of our environment and are of growing public concern because of their potential to enter the human body. There is still a small number of studies investigating the potential effects of MnP on human health, and very little is known about the health effects of inhaled MnP, as these particles have only recently been detected in human lung tissue despite the lungs being a potential major portal of MnP entry. There is therefore an urgent need to investigate the potential toxicological or immunomodulatory effects of inhaled MnP in healthy people and those with respiratory disease such as asthma.
Our labs aim to develop sophisticated and autologous in vitro co-culture models using primary human cells that can be used for the advanced in vitro testing of inhalable pollutants. In the scope of this PhD project, we will investigate the potential toxicity and immune modulation of the highly relevant airborne polypropylene (PP) and polyethylene terephthalate (PET). To this end, a personalised in vitro triple cell co-culture model will be established, with primary human differentiated nasal epithelial cells (HNEpCs), blood monocyte-derived macrophages (MDM) and dendritic cells (MDDC) from the same individual, mimicking the upper respiratory tract. The co-cultures will be exposed to thoroughly characterised fluorophore-labelled PP and PET MnP nebulised at the air-liquid interface. MnP trafficking, toxicity and interaction with immune cells will be monitored post-exposure using advanced fluorescence imaging, flow cytometry, RNA sequencing and protein expression analysis. Cells from both healthy donors and patients suffering from asthma will be used and responses will be compared.
- Establishment, characterization and optimization of air-liquid co-cultures with HNEpCs, MDM and MDDC.
- Optimization of exposure protocol employing MnP with the Vitrocell system.
- Assessment of MnP dose-range and analysis of dose-response.
- Investigate acute and sub-acute effects of low and high dose MnP in co-cultures of HNEpCs, MDM and MDDC at the ALI.
- Investigate acute and sub-acute effects in cultures from healthy and asthmatic donors (translational research).
Tel. +41 31 684 04 20
