Master Project (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:

  1. Establishing a 3D adipogenic spheroid model using sub and viscASC in mono-culture or in co-culture with macrophages.
  2. Adipogenic differentiation of ASC in 3D spheroid model in vitro. 
  3. Characterization of cell viability and adipogenic states under physiological and pathophysiological conditions in vitro. 
  4. Immunofluorescence staining of 3D spheroid microtissues for confocal/light sheet microscopy.
  5. Performing cell-based functional in vitro assays such as glycerol release (lipolysis), insulin stimulated leptin secretion, and lipogenesis.
  6. Analysis of specific markers on gene transcript and protein level of adipocyte spheroids using RNA next generation sequencing as well as lipidomics. 
  7. Analysis of cytokine/chemokine secretion by cells cultured in 3D spheroids. 
  8. Applying statistical analysis, interpreting results and presenting data.
  9. 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