Ruprecht Karls Universität Heidelberg

Seminar Biophysics of sensing, signaling and cell fate decisions

Content

Cells have remarkable abilities to respond to changes in their environment. This seminar focuses on signal reception and processing, including the consequences for cell fate decisions such as apoptosis and differentiation, from a mathematical and physical perspective. With the help of common biological model systems we will analyze qualitatively and quantitatively how cells sense and respond to their chemical, social and physical environment, discussing phenomena such as chemotaxis, quorum sensing control or mechano-sensing. We will elucidate the biophysical limitations of cellular information processing in each case and introduce key concepts that have enabled cells to successfully meet these challenges. With the help of generic biophysical models we will address: 1) how signals are sensed by allosteric receptors, 2) how information is processed by cellular signal transduction networks to extract biologically relevant information from such signals (bio-computing) and 3) how cells achieve specific and robust information transfer. We will apply these concepts to the different biological model systems using relevant data from the literature. The ultimate goal of the seminar is to provide students with the knowledge that should enable them to 1) make informed comparisons between different sensory systems, 2) to use biophysical insight for hypothesizing about common principles and system-specific “design solutions” that have evolved in nature and 3) to apply this knowledge for biotechnological applications in order to interfere with signaling or to rationally (re)engineer a sensory network (synthetic biology).

Required background

This seminar is targeted at advanced biology, biotechnology and physics students with an interest in interdisciplinary approaches. For the biology and biotechnology students, some mathematical knowledge on kinetic equations is helpful, but not required. For the physics students, some knowledge in statistical physics and biophysics is helpful, but not required. The seminar aims to build the foundation for fruitful and efficient interdisciplinary research of the participants. In order to take advantage from the expertise of the other field, students must learn how to effectively communicate with each other by developing a common terminology and appreciate the competencies of the other field.

Organization

This seminar is jointly organized by Ulrich Schwarz and Falko Ziebert (ITP and BioQuant) as well as Thomas Hoefer (DKFZ and BioQuant). We will meet for the first time on Monday April 15th 2019 at 4.15 pm to discuss the details of the course. Most likely we will run it as compact seminar with meetings in Dec and Jan. If you want to pre-register, send an email to Ulrich Schwarz (schwarz@thphys.uni-heidelberg.de).

Phenomena

  • Cell response to signaling molecules, including changes in gene expression
  • Chemotaxis of E coli
  • Chemotaxis of eukaryotic cells (Dictyostelium and neutrophils)
  • Mechanosensing and durotaxis of tissue cells
  • Apoptosis (programmed cell death)
  • Differentiation of different types of stem cells
  • etc

Concepts

  • Diffusion to capture
  • Positive feedback, bistability and ultrasensitivity
  • Network design
  • Physical limits of gradient sensing
  • Kinetic proofreading
  • etc

Literature

  • Alberts et al., Molecular Biology of the Cell (MBoC), Taylor and Francis 6th edition 2014
  • Rob Phillips, Jane Kondev, Julie Theriot, Hernan Garcia, Physical biology of the cell (PBoC), Garland Sciences 2nd edition 2012
  • Doug Lauffenburger and Jennifer Lindermann, Receptors: models for binding, trafficking, and signaling, Oxford University Press 1996
  • Howard Berg, Random walks in biology, Princeton University Press 1993
  • Robert Endres, Physical Principles in Sensing and Signaling: With An Introduction To Modeling In Biology, Oxford University Press 2013
  • William Bialek, Biophysics: Searching for Principles, Princeton University Press 2012
  • Uri Alon, An Introduction to Systems Biology: Design Principles of Biological Circuits, Chapman & Hall 2006