Information für die Wissenschaft Nr. 45 | 24. Juni 2015
Priority Programme “Iron-Sulfur for Life: Cooperative Function of Iron-Sulfur Centers in Assembly, Biosynthesis, Catalysis and Disease” (SPP 1927)
The Senate of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) has decided to establish a Priority Programme, entitled “Iron-Sulfur for Life: Cooperative Function of Iron-Sulfur Centers in Assembly, Biosynthesis, Catalysis and Disease”. The programme will commence in 2016 and is designed to run for six years. Applications are now invited for the first three-year funding period.
Iron-sulfur (FeS) centers are essential protein cofactors in all forms of life. In particular, FeS centers function as enzyme cofactors in catalysis and electron transfer. Moreover, they are indispensable for the biosynthesis of complex metal centers such as the iron-molybdenum cofactor (FeMoco) of nitrogenase, the molybdenum cofactor of various molybdoenzymes as well as the active sites of [FeFe]- and [Fe]-hydrogenases. In spite of recent fundamental breakthroughs in metalloenzyme research, it has become evident that studies on single enzymes need to be transformed into the broader context of a living cell where biosynthesis, function, and assembly/disassembly of these fascinating metal cofactors are coupled in a dynamic fashion. Various biosynthetic pathways were found to be tightly interconnected through complex crosstalk mechanisms that crucially depend on the bio-availability of the metal ions iron, molybdenum, tungsten, nickel, copper, and zinc. These metals are essential constituents for nitrogenase, hydrogenase and selected molybdo-/tungstoenzymes. Novel methodological developments shall allow for a detailed investigation of the biosynthesis and catalytic function of FeS-dependent enzymes in a cellular context, thus, opening up a new era in metalloenzyme studies. Moreover, cellular studies are a prerequisite for obtaining a comprehensive view on the involvement of metalloenzymes in metal-related human diseases. Further, the programme aims at the development of future cellular systems for bioenergy production, fertilisation and bio-applications. In order to adequately address these questions, novel, interdisciplinary concepts and approaches shall be combined with novel technological advancements.
Understanding the crosstalk of metal ions on a cellular basis requires multidisciplinary and cooperative approaches that span the entire range from cell and molecular biology, biochemistry, inorganic chemistry, spectroscopy, and structural biology to theory. In the Priority Programme it is planned to study novel enzyme mechanisms, innovative model complexes, and to define the mechanistic basis of the metal center biogenesis pathways in the (patho-)physiological context of living organisms.
The following fundamental areas will be addressed:
- assembly of complex FeS proteins as a starting point for versatile functionality
- biosynthesis and crosstalk of complex metal cofactors by FeS proteins
- catalysis and functions of complex FeS proteins for bio-applications
- disease-relevant, mechanistic roles of FeS proteins in cellular metal homeostasis
It is anticipated that in the four areas within the Priority Programme innovative studies will be supported towards answering key questions on:
- the crosstalk of metals in the assembly and biosynthesis of protein active site metal centers with a focus on the biosynthesis of generic FeS clusters, the molybdenum/tungsten cofactor, the iron-molybdenum cofactor, [NiFe], [FeFe] and [Fe] centers of hydrogenase and nitrogenase-like centers
- novel reactions of binuclear metal clusters in nitrogenase-like enzymes, hydrogenases and molybdoenzymes, the characterisation of “novel” FeS centers in proteins, in addition to “dual-function” activities of proteins in the biosynthesis of metal-cofactors with a role at the cellular level
- assembly and cofactor insertion of hydrogenases and complex FeS-containing enzymes with a focus on bio-applications
- studies on metal homeostasis and trafficking with a focus on the relevance of FeS clusters for cell survival and disease
- novel spectroscopic developments to study FeS-related proteins at a cellular level
It is expected that successful applications will propose visionary work on FeS center biogenesis, crosstalk and catalytic function, both in classic model systems and in disease-relevant systems. Further suitable applications encompass the study of complex FeS cluster-containing proteins (hydrogenase, nitrogenase, molybdoenzymes) including potential biotechnological applications. Collaborative studies across the four areas are crucial for integration into the Priority Programme.
The following research questions are excluded:
- studies on well-established metal centers involved in photosynthesis, respiratory chains or oxygenases, e.g., heme-containing enzymes
- studies on FeS-containing enzymes where the clusters have solely a structural role
- studies on medical iron-related diseases that solely study iron transport and do not directly address the biosynthesis of metal clusters or the activity of metal-cofactor containing enzymes
- studies on isolated, mono-functional FeS-containing enzymes that do not contain methodological developments to study more complex processes at a cellular level
- FeS-cluster-independent enzyme-systems containing metals other than Mo, W, Ni, Cu, Zn
Proposals for the first three-year funding period must be submitted in English no later than 30 September 2015 (deadline) via DFG’s electronic submission system “elan” selecting “SPP 1927”. Please follow the guidelines for project submission according to forms 50.05en and 54.01en. Please obey the rules for publication lists (form 1.91en). If you are using the “elan” system for the first time, please note that you need to register yourself and your institutional address before being able to submit a proposal. Also, if you are planning to move to a different institution you need to register the new institutional address beforehand. Please make sure that all applicants of your project (in case there is more than one) start their registration at the latest two weeks before the submission deadline. The registration requests are handled manually by DFG staff.
You are further asked to send a PDF file of the application as well as an additional PDF file of the summary of the main application to the coordinator of the Priority Programme.
The review will be held during a proposal colloquium scheduled to take place in Potsdam from 9 to 11 March 2016.
The DFG’s electronic portal “elan” can be found at:
Proposal instructions and guidelines can be found at:
For scientific enquiries please contact the coordinator of the Priority Programme:
- Prof. Dr. Silke Leimkühler,
Institut für Biochemie und Biologie,
phone +49 331 977-5603,
Link auf E-Mailsleim@uni-potsdam.de
For administrative enquiries please contact: