Benutzerspezifische Werkzeuge


Benutzerspezifische Werkzeuge

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Dynamics of Thiol-based Redox Switches in Cellular Physiology

Proposal Template for 2nd Funding Period


In recent years it has become evident that reactive oxygen and nitrogen species, despite their traditional reputation as components of radical chains and harbingers of damage, act as physiologically essential messengers in signal transduction. The signaling properties of particular oxidants are primarily sensed and mediated by 'protein thiol switches', which are protein thiols that are specifically and reversibly modified by oxidation, thereby switching the protein between different conformational and functional states. In spite of the fundamental cell biological and medical importance of thiol switches we are only beginning to understand their principles of specificity, their mechanism of action, and their role in the spatio-temporal operation of signal transduction. Based on this new perception and recent pioneering technical developments, an interdisciplinary consortium of more than 30 scientists joined forces within the SPP1710 to synergistically address the following fundamental questions in the field of redox signaling and thiol-based redox regulation:


What are the molecular mechanisms underlying protein thiol switches, and how can we explain their specificity and efficiency?


Which redox signaling events and thiol switch changes do occur in the living organism and what are the species-specific differences?


What are the physiological roles of redox signals within the overall cellular signaling circuitry and decision making?


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Dynamic Thiol Switches


In order to adequately address these questions, novel interdisciplinary concepts and approaches will be combined with stringent technological advancement:


  • We plan to clarify the precise biochemistry of the events under study.
  • We plan to obtain high-resolution structural, functional, quantitative, and spatio-temporal information on in vivo redox events and their dynamics.
  • We plan to identify, monitor, and specifically manipulate individual thiol switches in vivo.


Within the SPP 1710, expertise, chosen experimental approaches, and technology is exchanged and made available in a highly synergistic way aiming to cross the borders between disciplines, between subcellular compartments, between thiol switch proteins of interest, and between model organisms – ranging from bacteria, protozoa, yeast and plants to mammals. The priority program comprises individual groups and projects approaching the joint interest in thiol switches from different angles.



Area 1: Projects characterizing newly identified thiol switches, which are to be studied in mechanistic, functional, and structural detail.


Area 2: Projects identifying as yet unknown thiol switches, which are predicted to exist in a particular functional context and are planned to be characterized.


Area 3: Projects developing and applying engineered thiol switches to monitor (patho)physiological redox signaling in vivo.


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Major Thiol Switches, Model Organisms and Compartments

    Based on the planned experiments and the synergistic exchange between the groups, we aim to establish standardized methods in redox research. In the medium to long term our goal will be to obtain a more complete picture of thiol switch proteins, mechanisms and regulation of thiol switching, thiol switch-dependent pathways, and their integration into signal transduction and metabolism.