Stem cell population dynamics in non-homeostatic tissues

• Applicant: Dr. Philip Greulich
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics ; Bioinformatics and Theoretical Biology ; Biophysics
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 229203819

The project aims at quantifying the role and dynamics of stem cell populations in tumour onset/progression and developing tissue. This will be approached by linking methods of theoretical physics to experiments, which are performed by collaborating biologists.Stem cells are able to reproduce by renewing, and to differentiate into specialised cell types (cell fate). Therefore, they play an essential role in tissue maintenance, biological development, and, potentially, in tumour growth. While tissue maintenance is a stationary (homeostatic) process, development and tumour onset are non-stationary (non-homeostatic) processes which are characterised by predominant growth. Whereas a closed theory of cell fate decisions exists for stem cell populations in homeostatic tissues, it is still outstanding for non-homeostatic ones.The planned project involves the elaboration of a stochastic theory for stem cell fate decisions and the resulting cell population dynamics in non-homeostatic situations. The key for unravelling the rules of cell fate decisions is to identify their 'fingerprint' in the robust spatio-temporal (scaling) properties of stem cell population distributions. The project seeks to determine the universal scaling features of the considered stochastic models by methods of theoretical physics, and to compare (e.g. by using Bayesian inference) with the available experimental cell lineage data from certain non-homeostatic tissues (e.g. intestinal tumours, developing intestinal tissue). In this process, the model structure is steadily adapted to the data, and, by finally matching the stochastic (microscopic) theory to the measured stem cell population data, we seek to find the underlying laws of cell fate decisions. In particular, the project approach is suited to address the question whether only a small population of stem cells drives tumour growth (cancer stem cell hypothesis) and how they are distributed. This information may help to improve the accuracy of anti-cancer treatments and diagnostics.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Benjamin Simons