Master Project 1 (100 %):
Development and characterization of adipose spheroids to model obesity-related metabolic disorders
Background:
Obesity has become a serious health problem worldwide and is one of the major reasons for reduced life expectancy within the “modern” society. The most common obesity-associated serious metabolic complication called “insulin resistance syndrome” increases the risk for developing hyperglycemia, hyperinsulinemia, glucose intolerance, liver fat accumulation, and dyslipidemia, and endothelial dysfunction. Therefore, there is a significant need for a robust in vitro adipose tissue model that faithfully reproduces human physiology and pathophysiology to prevent and/or treat these disorders.
Objective:
To develop a human 3D adipose tissue in vitro spheroid model that mimics the microenvironmental and cellular complexity of human fat.
Methods:
The project aims to develop 3D in vitro spheroid model of adipose tissue using human primary subcutaneous (sub) and visceral (visc) adipose mesenchymal stem cells (ASC) in vitro. The sub/visc ASC will be used in mono-culture or co-cultured with human macrophages. Furthermore, the generated adipogenic spheroids will be characterized using state-of-the-art biochemical and molecular techniques.
Hypothesis:
The proposed 3D spheroid fat model will allow organomimetic 3D co-culture of two main types of adipocytes: subcutaneous and visceral cells in a close to physiological arrangement.
Your responsibilities:
- Establishing a 3D adipogenic spheroid model using sub and viscASC in mono-culture or in co-culture with macrophages.
- Adipogenic differentiation of ASC in 3D spheroid model in vitro.
- Characterization of cell viability and adipogenic states under physiological and pathophysiological conditions in vitro.
- Immunofluorescence staining of 3D spheroid microtissues for confocal/light sheet microscopy.
- Performing cell-based functional in vitro assays such as glycerol release (lipolysis), insulin stimulated leptin secretion, and lipogenesis.
- Analysis of specific markers on gene transcript and protein level of adipocyte spheroids using RNA next generation sequencing as well as lipidomics.
- Analysis of cytokine/chemokine secretion by cells cultured in 3D spheroids.
- Applying statistical analysis, interpreting results and presenting data.
- Supervised planning and writing of final repor.
Your profile:
Interested and motivated student. Background in life sciences.
What we offer:
We offer a varied and interesting work in an inspiring and socially relevant environment. Place of work University of Zurich, Schlieren Campus, Wagistrasse 12, 8952 Schlieren, Switzerland Start of employment
Earliest start:
March 2022, duration of Master thesis: 9-15 months. For foreign students, applications for funding from the Swiss-European Mobility Programme (SEMP) are possible for all traineeships within Europe.
For further information and applications, please contact
PD Dr. Agnes Klar
Agnes.klar@kispi.uzh.ch
