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Controlled patterning of organoids
During development cells must assume different fates in a position-dependent manner. Morphogen gradients are able to encode this positional information, in order to guide tissue patterning during embryonic development. In the French flag model of patterning, morphogen concentration levels determine tissue domains of different cell fates. However, current in vitro 3D cell models fail to reproduce the patterning observed in vivo. Our aim is to generate 3D cell models which are able to reproduce patterning, thus allowing us to study morphogen gradients in diverse stages of development.
In this project, we aim at establishing controlled and physiologically relevant morphogen gradients to guide 3D cell models development (e.g., organoids, gastruloids). To this end, we will employ microengineered platforms able to support organoid development and their exposure to predictable gradients of small molecules to control organoid patterning.
The student will first design and simulate the behavior of such advanced culturing platform, then he/she will proceed with their fabrication, characterization and, ultimately, use in cell organoid culturing. The platforms will be fabricated using micromachining and surface functionalization to control the behavior of liquids in microchannels. Platform characterization will be carried out using fluorescent tracers to monitor the establishment of gradients of small molecules in artificial extracellular matrices. Organoid patterning will be confirmed by immunofluorescence staining and subsequent imaging in confocal and/or lightsheet microscopes.
What you will learn:
- 3D CAD design and finite-element-method simulation
- Surface functionalization
- Handling of microfluidic cell-culturing platforms
- Culturing of 3D cell-culture models
- Immunofluorescence staining and microscopy
In this project, we aim at establishing controlled and physiologically relevant morphogen gradients to guide 3D cell models development (e.g., organoids, gastruloids). To this end, we will employ microengineered platforms able to support organoid development and their exposure to predictable gradients of small molecules to control organoid patterning. The student will first design and simulate the behavior of such advanced culturing platform, then he/she will proceed with their fabrication, characterization and, ultimately, use in cell organoid culturing. The platforms will be fabricated using micromachining and surface functionalization to control the behavior of liquids in microchannels. Platform characterization will be carried out using fluorescent tracers to monitor the establishment of gradients of small molecules in artificial extracellular matrices. Organoid patterning will be confirmed by immunofluorescence staining and subsequent imaging in confocal and/or lightsheet microscopes. What you will learn: - 3D CAD design and finite-element-method simulation - Surface functionalization - Handling of microfluidic cell-culturing platforms - Culturing of 3D cell-culture models - Immunofluorescence staining and microscopy
Our aim is to generate 3D cell models which are able to reproduce patterning, thus allowing us to study morphogen gradients in diverse stages of development
Our aim is to generate 3D cell models which are able to reproduce patterning, thus allowing us to study morphogen gradients in diverse stages of development
Mario Modena: mario.modena@bsse.ethz.ch
Doumpas Nikolaos: nikolaos.doumpas@bsse.ethz.ch
Mario Modena: mario.modena@bsse.ethz.ch Doumpas Nikolaos: nikolaos.doumpas@bsse.ethz.ch