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    SPP 2389: Verständnis und Steuerung der zellulären Spezialisierung in leitfähigen multizellulären Strukturen
    Conductive biofilms are produced by organisms that flourish in nature using insoluble electron acceptors, such as ferric or manganese oxides, as terminal electron acceptors of their respiratory chain. This conductivity allows cells that are not in direct contact with the electron acceptor to transfer respiratory electrons to neighbouring. The redox potential gradient then guides the electron flow through the matrix towards the point of highest redox potential, which is typically the mineral. Cells within these materials undergo specialization potentially due to: (I) thickness and cell density of the biofilm leading to cell-cell signalling as well as mass transfer limitation of the electron donor from the bulk phase, (II) respiratory electron transfer operating with different kinetics due to increasing resistance with electron transport length, (III) gradients forming, as in the case of pH, leading to growth with different kinetics and (IV) shear force leading to biofilm compression but also necessitating the formation of a stronger extracellular matrix. Currently, it's not understood how these factors influence the development of different regulatory routines that drive cellular specialization. Nevertheless, at a more phenomenological level, we observe these routines as cells construct different conductive structures based on their proximity to the terminal electron acceptor. We also observe that some layers in these conductive biofilms are primarily composed of non-living cells, yet these layers still function as conductive structures. Our goal is to decipher the triggers and regulatory mechanisms within individual cells that lead to the formation of these stable, dynamic conductive biofilm structures. A fundamental understanding of these processes will significantly impact how we perceive these structures in ecosystems, where they can have critically important functions. To reach our goal we will use multiparallel microfluidic bioelectrochemical experiments conducted with reporter strains and will use FACS coupled to transcriptomic analyses to understand regulatory routines. Moreover, we will aim to understand how these conductive biofilms interact conductively with other cells enabling new physiological features.
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    SPP 2494: Streptomyces bioFilms - Biosynthesis, composition and their potential as productive systems in tubular Bioreactors
    Streptomyces are considered as ‘biofactories’ of secondary metabolites and are therefore extensively used in industrial biotechnology for the production of compounds with important biological activities in medicine, food industry and agronomy. These bacteria are prominent members of the soil microbiome with a fascinating developmental biology involving a complex transition from filaments to spores. In industrial bioprocesses they are mostly cultivated in large scale stirred-tank bioreactors as planktonic cells. However, because of their filamentous nature, maintaining optimal cultivation conditions for high productivity is often challenging due to the formation of cell clumps. In their natural habitat soil, Streptomyces exist in biofilms, but little is known about the formation, composition and regulation of biofilms in this genus. Moreover, the experience with Streptomyces biofilms for production of antibiotics in bioreactors is also extremely limited. In this interdisciplinary proposal, the synergetic combination of a molecular microbiologist and an expert in bioprocess engineering provides a unique possibility to study the mechanisms of biofilm formation in Streptomyces and additionally get important insights about robustness, responsiveness and productivity of these biofilms in bioreactors especially in response to bioprocess gradients of different kind. As Streptomyces physiology is diverse, to advance our knowledge about biofilm formation and composition, we will study different Streptomyces models (S. venezuelae, S. griseus and S. coelicolor) for antibiotics production and build on our preliminary data showing that in S. venezuelae c-di-GMP induces extracellular matrix (ECM) formation through a novel matrix synthase complex. We will isolate the extracellular matrix and analyze its composition and biophysical properties and investigate how antibiotic titers are affected by the ECM. We plan to achieve a breakthrough in Streptomyces application as cell factories and will establish two millilitre scale 3D-printed tubular flow bioreactor setups for productive Streptomyces biofilms to analyse how different bioprocess gradients in vertical and horizontal direction affect biofilm robustness, productivity and physiology on population and single cell level. For that purpose, we will analyse key performance parameters but also apply fluorescent reporter strain, whose fluorescence will be monitored via fluorescence microscopy and omics analysis. Altogether, our combined complementary expertise and strong preliminary data represent a powerful and unique baseline for understanding and application of Streptomyces biofilms for production of antibiotics with the aim to increase productivity of industrially important drugs for human benefits.
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    Verifikation im Bereich des Biowaffenübereinkommens neu denken (Teilvorhaben: Interdisziplinäre Beiträge zu einem Verifikationsmechanismus im Biowaffenübereinkommen - Bioinformatik und Sozialwissenschaften)
    VERIBIO setzt sich mit den Herausforderungen für einen möglichen ex ante Verifikationsmechanismus des Biowaffenübereinkommens im industriellen Bereich auseinander. Biowaffen-relevante Aktivitäten staatlicher und privater Akteure sollen frühestmöglich erkannt werden. VERIBIO bearbeitet das Problem interdisziplinär mit dem Ziel ein proof of concept für ein compliance bezogenes Monitoring industrieller Biosyntheseverfahren zu erstellen. Es soll erforscht werden, ob Daten aus dem Produktionsprozess automatisiert ausgelesen und dahingehend analysiert werden können, dass festgestellt werden könnte, wenn in der Anlage illegitime Produkte in einem fermentationsbasierten Syntheseprozess erzeugt werden
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