In vitro polarization of the proximal tubule: functional implications in health and disease
This project is dedicated to unravelling the intricate relationship between cellular polarisation and functional outcomes in epithelial cells. Renal tubular epithelial cells play a critical role in maintaining kidney function, and disruptions in their polarisation can have profound implications for health and disease. As highly motivated PhD fellow you will join our team and contribute to this cutting-edge research endeavour.
You will work on understanding how the polarisation of proximal tubular epithelial cells influences their functionality in both health and disease. Polarisation refers to the establishment of distinct membrane domains in epithelial cells, crucial for their specialised functions in reabsorbing and secreting solutes, maintaining electrolyte balance, and regulating transport processes within the kidney.
Your primary objectives will include:
Development of genetically modified tubular epithelial cell lines using the Crispr-Cas9 system to mimic renal tubulopathies, with a specific focus on perturbations in cell polarisation.
Evaluate downstream pathways, such as autophagy, apoptosis, glucose metabolism, and metabolite absorption/secretion, in the context of polarised versus non-polarised renal tubular epithelial cells.
Determine substrate features that support polarisation: Investigate how different 3D substrates, both chemically and biomechanically defined, influence tubule formation and phenotypic traits, including barrier function and transport capacity, in polarised epithelial cells.
Analysis of recovery of functional polarisation upon injury: Examine the ability of polarised cells to recover transepithelial function following injury, particularly in relation to the restoration of cell polarity.
To accomplish these objectives, you will utilise advanced 3D cell culturing methodologies. Additionally, you will employ state-of-the-art techniques for structural and functional characterisation of proximal tubule transport. Furthermore, you will gain expertise in microfluidics and biofabrication technologies, allowing for In Vitro transepithelial transport studies and drug interaction assessments in polarised cells.