Projekt

Cell decision-making is the process of cells changing their phenotype according to their intrinsic programming and in response to the micro-environmental cues. Currently, little is known about the principles dictating cell decision-making in multicellular systems. Regarding cells as Bayesian decision-makers under energetic constraints, this work proposes that organisms of all domains of life operate using a "Least microEnvironmental Uncertainty Principle (LEUP)" for their decision-making processes. This is translated into a free-energy principle, implying a statistical mechanics theory for cell decision-making. Here, three fundamental challenges will be addressed: a) the uncertainty/ stochasticity of subcellular regulatory cell decision-making mechanisms; b) lack of knowledge in the relative contribution of intrinsic and extrinsic cell decision-making factors to multicellular spatiotemporal dynamics; c) a unified theory for different types of cell decision-making. Such a statistical mechanics reduction allows for simplifying many parameters into a low-dimensional mathematical description and circumvent the uncertainty about the underlying mechanisms. Moreover, it allows integrating heterogeneous types of data as constraints of LEUP energy optimization. Using LEUP in close relation to experiments enables to determine model details for different general cell decision-making problems: (i) cell fate determination of hematopoietic stem cells, (ii) local interactions during T-cell differentiation, (iii) macrophage phenotypic plasticity and (iv) flagella assembly during bacterial cell division.

• Dr. Haralampos Hatzikirou

  Technische Universität Dresden
  Zentrum für Informationsdienste und Hochleistungs-
  rechnen (ZIH)
  Andreas-Pfitzmann-Bau
  Dresden
  

• Prof. Dr. Massimo Locati, MD

  Università degli Studi di Milano
  Department of Medical Biotechnology and
  Translational Medicine
  Milan
  Italien
  

• Prof. Dr. Marc Erhardt

  Humboldt-Universität Berlin
  Institut für Biologie
  Bakterienphysiologie
  Haus 22
  Berlin
  

• Prof. Benjamin Geiger, Ph.D.

  The Weizmann Institute of Science
  Faculty of Biology
  Department of Immunology
  Wolfson Building
  Rehovot
  Israel
  

• Dr. Ioannis Mitroulis, MD

  Technische Universität Dresden
  Medizinische Fakultät
  Institut für Klinische Chemie und
  Laboratoriumsmedizin
  Dresden