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Structural analysis: Publication in ACS Sensors
In order to understand metabolic processes, it is important to be able to detect critical individual elements and metabolites in living organisms. Researchers from Heinrich Heine University Düsseldorf (HHU) have now developed a new computational method for designing biosensors for such analysis. They now describe the novel iron sensor “IronSenseR”, which has been realised in this way, in the scientific journal ACS Sensors.
Iron is an essential trace element in biological cells. The concentration of the element and its so-called redox state – it can exist either in a doubly ionised state as iron (II) (Fe2+) or a triply ionised state as iron (III) (Fe3+) – play a key role in metabolic processes such as cellular respiration and in microbial stress responses.
Dr Athanasios Papadopoulos, lead author of the studies, which have now been published in ACS Sensors: “The ability to observe labile iron in vivo in real time and at a high level of specificity has been extremely limited to date. Our new ‘IronSenseR’ biosensor now makes it possible to conduct such experiments and research the distribution and function of iron in living cells.”
A research team from the Center for Structural Studies (CSS) at HHU has developed a novel, computer-based method called “CoBiSe” to design and produce genetically encoded fluorescence-based biosensors in a rapid and simple approach. The authors now describe the highly selective biosensor “IronSenseR” for iron (II) designed using the method. The biosensor was successfully inserted into various bacterial systems – including Escherichia coli, Pseudomonas putida and Corynebacterium glutamicum – in order to observe changes in the intracellular iron pool. The application studies were realised in collaboration with the research groups led by Professor Dr Julia Frunzke, Professor Dr Thomas Drepper and Professor Dr Michael Bott, together with the Center for Advanced Imaging (CAi).
“This represents significant progress in the development of biosensors, a process known as biosensor design,” emphasises corresponding author Professor Dr Sander Smits. “It enables us to improve our understanding of the dynamics of iron in living cells.”
Dr Christoph G. W. Gertzen, the second corresponding author, adds: “The biosensor enables precise iron metabolism measurements, which in turn enable further research into iron-related medical conditions, among other things. This successful development offers hope that ‘CoBiSe’ can also be used for the rapid production of genetically encoded biosensors for other metabolites and metal ions, and beyond that, also other tailored proteins such as enzymes.”
New method for biosensor development: “CoBiSe – Computational Biosensor Design”
CoBiSe is a computational, structure-based approach. It can be used for the targeted identification of sites on binding proteins – which bind selectively to interesting biological structures – in which biosensor cassettes can subsequently be embedded. These cassettes ultimately carry the fluorescent molecules, which can for example be made visible under the microscope, revealing the location of the biological structures being sought. It is important that these biosensor cassettes do not impact the function of the binding proteins. Smits: “In comparison with conventional methods, which involve complex and time-consuming experiments, CoBiSe significantly reduces the workload and time required to develop functional biosensors, ensuring they can be used in practice more quickly.”
The iron biosensor IronSenseR developed in this way detects iron (II) with a high level of sensitivity without binding to iron (III) or other metal ions.
Integration into the Collaborative Research Centre MibiNet
The project was established within the framework of the Collaborative Research Centre CRC 1535 MibiNet based at HHU, which conducts research into microbial networks. Metabolite-based communication channels between microbes are of great importance here. The biosensors developed in the central project (Z01) – realised by CSS in collaboration with CAi – are an outstanding and non-invasive molecular tool for tracking dynamic changes in important metabolites in living cells.
Athanasios Papadopoulos, Manuel T. Anlauf, Jens Reiners, Seung-Hyun Paik, Aileen Krüger, Benita Lückel, Michael Bott, Thomas Drepper, Julia Frunzke, Holger Gohlke, Stefanie Weidtkamp-Peters, Sander H. J. Smits, Christoph G. W. Gertzen; A Novel Biosensor for Ferrous Iron Developed via CoBiSe: A Computational Method for Rapid Biosensor Design; ACS Sensors (2026)
DOI: 10.1021/acssensors.5c02481
https://www.sfb1535.hhu.de/en/
Schematic diagram of the CoBiSe approach for the structure-based identification of suitable insertio ...
Copyright: HHU/Athanasios Papadopoulos
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