About the Project
Bioengineering kidney tubules: For tubular organs tissue shape and positioning during embryogenesis is an essential determinant of function. The biomechanics of tubulogenesis is not well understood, but studying kidney morphogenesis in vertebrates is technically challenging. Drosophila Melanogaster embryonic Malpighian tubules offer a powerful model system which we will use in this project. Our preliminary data support a biomechanical role for the extracellular matrix (ECM) proteins in…
maintaining tubule shape in vivo. We will bioengineer an innovative system to support ex vivo tubule growth to elucidate how biomechanical forces generated by synthetic ECM drives tubulogenesis. This interdisciplinary project will be done in collaboration with the group of Fredrik Schaufelberger in Chemistry (experts in generating functionalized ECM scaffolds) and the Koester lab at WMS (expert in generating biomimetic systems).
Aim 1: To gain a better spatio-temporal understanding of biomechanics, we will bioengineer a system to study tubule growth ex vivo. We will design microfabricated 2D and 3D scaffolds functionalized with ECM proteins or synthetic ECM-like peptides to support dissected tubules. This will generate a system which is easy to visualise, manipulate and have tremendous future applications.
Aim 2: How does ECM composition regulate tissue stiffness and tubule morphogenesis? We will culture tubules dissected out from wildtype and various ECM mutant embryos to measure tubule stiffness during elongation using Atomic Force Microscope and image long term growth using light sheet imaging.
Aim 3: Dissect the role of ECM in force distribution. We will measure forces and perturb the spatial distribution of tension including membrane permeable fluorescence-based force sensors, laser ablation and through local application of molecular inhibitors.
