Information für die Wissenschaft Nr. 55 | 15. September 2016
Dynamics of Thiol-based Redox Switches in Cellular Physiology (SPP 1710)
The Senate of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) has established the Priority Programme “Dynamics of Thiol-based Redox Switches in Cellular Physiology” (SPP 1710). The programme is designed to run for six years. The present call invites proposals for the second three-year funding period.
Over the last years it has become evident that reactive oxygen and nitrogen species act as physiologically essential messengers in signal transduction. The signalling 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 operation and specificity, their spatio-temporal dynamics, and their role in overall signal transduction. Based on this perception and recent pioneering technical developments, particularly in redox imaging, redox proteomics and redox bioinformatics, we aim to synergistically address the following fundamental questions in the field of redox signalling and thiol-based redox regulation:
- What are the molecular mechanisms underlying protein thiol switches, and how can we explain the specificity and efficiency of reversible thiol switch oxidation and reduction?
- Which redox signalling events and thiol switch changes do occur in living organisms? Which redox switches are conserved and which are species-specific?
- What are the physiological roles of redox signals within the overall cellular signalling circuitry and decision making?
In order to adequately address these questions, novel interdisciplinary concepts and approaches shall be combined with stringent technological advancement:
- The precise biochemistry of the events under study shall be defined.
- High-resolution structural, functional, quantitative, and spatio-temporal information on in vivo redox events and their dynamics shall be obtained.
- Individual thiol switches shall be identified, monitored, and specifically manipulated in vivo.
- The physiological roles of thiol-switches shall be defined.
The Priority Programme aims to catalyse a decisive transition towards a true and thorough understanding of redox signalling cascades in the coming years. For this Priority Programme we propose an assembly of scientists uniquely positioned and selected for the task at hand, because of their conceptual and/or technical leadership. Within the programme, expertise and technology will be exchanged and made available in a highly synergistic way aiming to cross the borders between disciplines and to identify common principles of thiol switching across different model organisms – ranging from bacteria, protozoa, yeast and plants to mammals. A well-balanced analysis of model systems shall enable the programme to define and to examine general redox signalling concepts of thiol switching, and at the same time, the rapid exchange and translation of results will speed up our understanding of thiol switching in the different model systems.
It is anticipated that within the Priority Programme substantial progress will be made towards answering key questions on:
- how oxidant signals actually propagate within cells,
- how thiol switches are mechanistically operated, and
- how redox signalling typically intersects with other forms of signalling, e.g., protein phosphorylation or acetylation.
The group will be able to compare redox signalling processes in different subcellular compartments and organisms and place them in a phylogenetic/evolutionary framework. It is expected that the in-depth unravelling of functional thiol switches, from the biophysical level to whole-organism physiology, will reveal general principles that may become paradigmatic for the entire field and have great potential for biomedical or agronomical translation.
The projects of the Priority Programme may be categorised into three classes:
- Projects characterising newly identified thiol switches, which are to be studied in mechanistic, functional, and structural detail.
- Projects identifying as yet unknown thiol switches, which are predicted to exist in a particular functional context and are planned to be characterised.
- Projects developing and applying engineered thiol switches to monitor (patho)physiological redox signalling in vivo.
It is expected that the proposals provide clear visionary aims.
The following research questions should be excluded:
- General studies on oxidative or nitrosative stress in (patho)physiological contexts.
- Studies based on broad notions of “oxidative stress” or “ROS” that do not explicitly define or address chemistry, specificity, mechanism and in vivo relevance.
- Studies on free radical biology and chemistry which do not directly address thiol switches.
- Studies on redox-based intervention therapies which do not directly address thiol switches.
- Studies on irreversible thiol modifications.
Proposals for the second three-year funding period, to be written in English, must follow the guidelines in DFG forms 50.05en (Priority Programmes, Part B) and 54.01en (Project Proposals). The deadline for proposal submission is 15 January 2017. Proposals must be submitted via the DFG’s electronic submission system “elan”, selecting “SPP 1710”. A proposal template is available on the website of the Priority Programme.
If you are using the “elan” system for the first time, please note that you need to register yourself and your institutional addresses before being able to submit a proposal. If you are planning to move to a different institution (e.g. with a temporary position for principal investigators) you need to register with the address of the new institution. Please make sure that all applicants of your project start their registration at latest two weeks before the submission deadline as registration requests are taken care of manually by DFG staff.
The review will be held during a proposal colloquium scheduled to take place in Bonn from 3 April to 5 April, 2017.
The website of the Priority Programme with a proposal template can be found at:
Please submit proposals electronically through the DFG’s elan portal:
The DFG forms 50.05en and 54.01en can be downloaded at:
For scientific inquiries concerning the scope of the Priority Programme, please contact the programme’s coordinator:
- Prof. Dr. Katja Becker
Justus-Liebig-Universität Gießen, Interdisziplinäres Forschungszentrum, Arbeitsgruppe Biochemie und Molekularbiologie
phone +49 641 99-39121
Contact persons at the DFG:
For funding enquiries:
- Dr. Nikolai Raffler, phone +49 228 885-2441, firstname.lastname@example.org
For administrative enquiries: