MBI PhD Oral Defence
Time: 9AM
Date: Wednesday, 29 January 2020
Venue: T-Lab Building, Level 5 Meeting Room 1
Supervisor: Prof. Viasnoff Virgile
INVESTIGATING THE MECHANISMS GOVERNING THE INITIATION AND EXPANSION OF BILE CANALICULI
Bile canaliculi (BC), the secretory lumen enclosed by the apical domain of two adjacent polarized hepatocytes, are the structure basis for various liver function. Abnormalities in the establishment and maintenance of BC structure have been associated with diseases such as cholestasis and liver cancer. As other epithelial tubes found in kidney and lung, BC are generated through a process termed de novo lumenogenesis, by which the participating unpolarized hepatocytes acquire apical basal polarity and form bile acid filled apical lumen. However, how individual hepatocyte initiates apical-basal polarity in response to external cues remain poorly understood.
In this thesis, a 3D single hepatocyte culture system was created to precisely control the biochemical and physical properties of external cues presented to each cell. I found that individual hepatocyte developed fully functional luminal domain when cultured with access to spatially segmented cadherin and ECM signaling. Combined with data from co-culture assay, I demonstrated that cell polarity is largely a cell autonomous process, independent of the nature of neighboring cells and the polarity state of triggering signaling. Mechanistically, actin cortex rearrangements regulated by the biophysical properties and density of cadherins at the initial cell-cell junction is critical for the correct localization of polarity markers. Moreover, the creation of this single cell model provides unprecedented imaging resolution to observe the development of apical pole at the early stages of lumenogenesis process. Altogether, the reductionist approach demonstrated that single hepatocyte can be fooled into a functional polarized state by fine-tuning artificial microniches.
**Please note the examination following the seminar is closed-door**
