@inproceedings{7147, abstract = {The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets. In this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest. The behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions.}, author = {Guet, Calin C and Henzinger, Thomas A and Igler, Claudia and Petrov, Tatjana and Sezgin, Ali}, booktitle = {17th International Conference on Computational Methods in Systems Biology}, isbn = {9783030313036}, issn = {1611-3349}, location = {Trieste, Italy}, pages = {155--187}, publisher = {Springer Nature}, title = {{Transient memory in gene regulation}}, doi = {10.1007/978-3-030-31304-3_9}, volume = {11773}, year = {2019}, } @article{138, abstract = {Autoregulation is the direct modulation of gene expression by the product of the corresponding gene. Autoregulation of bacterial gene expression has been mostly studied at the transcriptional level, when a protein acts as the cognate transcriptional repressor. A recent study investigating dynamics of the bacterial toxin–antitoxin MazEF system has shown how autoregulation at both the transcriptional and post-transcriptional levels affects the heterogeneity of Escherichia coli populations. Toxin–antitoxin systems hold a crucial but still elusive part in bacterial response to stress. This perspective highlights how these modules can also serve as a great model system for investigating basic concepts in gene regulation. However, as the genomic background and environmental conditions substantially influence toxin activation, it is important to study (auto)regulation of toxin–antitoxin systems in well-defined setups as well as in conditions that resemble the environmental niche.}, author = {Nikolic, Nela}, journal = {Current Genetics}, number = {1}, pages = {133--138}, publisher = {Springer}, title = {{Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system}}, doi = {10.1007/s00294-018-0879-8}, volume = {65}, year = {2019}, } @article{196, abstract = {The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. }, author = {Lang, Moritz and Shkolnikov, Mikhail}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {8}, pages = {2821--2830}, publisher = {National Academy of Sciences}, title = {{Harmonic dynamics of the Abelian sandpile}}, doi = {10.1073/pnas.1812015116}, volume = {116}, year = {2019}, } @misc{7016, abstract = {Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature.}, author = {Tomanek, Isabella}, keywords = {Escherichia coli, gene amplification, galactose, DOG, experimental evolution, Illumina sequence data, FACS data, microfluidics data}, publisher = {Institute of Science and Technology Austria}, title = {{Data for the paper "Gene amplification as a form of population-level gene expression regulation"}}, doi = {10.15479/AT:ISTA:7016}, year = {2019}, } @phdthesis{6371, abstract = {Decades of studies have revealed the mechanisms of gene regulation in molecular detail. We make use of such well-described regulatory systems to explore how the molecular mechanisms of protein-protein and protein-DNA interactions shape the dynamics and evolution of gene regulation. i) We uncover how the biophysics of protein-DNA binding determines the potential of regulatory networks to evolve and adapt, which can be captured using a simple mathematical model. ii) The evolution of regulatory connections can lead to a significant amount of crosstalk between binding proteins. We explore the effect of crosstalk on gene expression from a target promoter, which seems to be modulated through binding competition at non-specific DNA sites. iii) We investigate how the very same biophysical characteristics as in i) can generate significant fitness costs for cells through global crosstalk, meaning non-specific DNA binding across the genomic background. iv) Binding competition between proteins at a target promoter is a prevailing regulatory feature due to the prevalence of co-regulation at bacterial promoters. However, the dynamics of these systems are not always straightforward to determine even if the molecular mechanisms of regulation are known. A detailed model of the biophysical interactions reveals that interference between the regulatory proteins can constitute a new, generic form of system memory that records the history of the input signals at the promoter. We demonstrate how the biophysics of protein-DNA binding can be harnessed to investigate the principles that shape and ultimately limit cellular gene regulation. These results provide a basis for studies of higher-level functionality, which arises from the underlying regulation. }, author = {Igler, Claudia}, issn = {2663-337X}, keywords = {gene regulation, biophysics, transcription factor binding, bacteria}, pages = {152}, publisher = {Institute of Science and Technology Austria}, title = {{On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation}}, doi = {10.15479/AT:ISTA:6371}, year = {2019}, } @article{305, abstract = {The hanging-drop network (HDN) is a technology platform based on a completely open microfluidic network at the bottom of an inverted, surface-patterned substrate. The platform is predominantly used for the formation, culturing, and interaction of self-assembled spherical microtissues (spheroids) under precisely controlled flow conditions. Here, we describe design, fabrication, and operation of microfluidic hanging-drop networks.}, author = {Misun, Patrick and Birchler, Axel and Lang, Moritz and Hierlemann, Andreas and Frey, Olivier}, journal = {Methods in Molecular Biology}, pages = {183 -- 202}, publisher = {Springer}, title = {{Fabrication and operation of microfluidic hanging drop networks}}, doi = {10.1007/978-1-4939-7792-5_15}, volume = {1771}, year = {2018}, } @article{723, abstract = {Escaping local optima is one of the major obstacles to function optimisation. Using the metaphor of a fitness landscape, local optima correspond to hills separated by fitness valleys that have to be overcome. We define a class of fitness valleys of tunable difficulty by considering their length, representing the Hamming path between the two optima and their depth, the drop in fitness. For this function class we present a runtime comparison between stochastic search algorithms using different search strategies. The (1+1) EA is a simple and well-studied evolutionary algorithm that has to jump across the valley to a point of higher fitness because it does not accept worsening moves (elitism). In contrast, the Metropolis algorithm and the Strong Selection Weak Mutation (SSWM) algorithm, a famous process in population genetics, are both able to cross the fitness valley by accepting worsening moves. We show that the runtime of the (1+1) EA depends critically on the length of the valley while the runtimes of the non-elitist algorithms depend crucially on the depth of the valley. Moreover, we show that both SSWM and Metropolis can also efficiently optimise a rugged function consisting of consecutive valleys.}, author = {Oliveto, Pietro and Paixao, Tiago and Pérez Heredia, Jorge and Sudholt, Dirk and Trubenova, Barbora}, journal = {Algorithmica}, number = {5}, pages = {1604 -- 1633}, publisher = {Springer}, title = {{How to escape local optima in black box optimisation when non elitism outperforms elitism}}, doi = {10.1007/s00453-017-0369-2}, volume = {80}, year = {2018}, } @article{503, abstract = {Buffers are essential for diluting bacterial cultures for flow cytometry analysis in order to study bacterial physiology and gene expression parameters based on fluorescence signals. Using a variety of constitutively expressed fluorescent proteins in Escherichia coli K-12 strain MG1655, we found strong artifactual changes in fluorescence levels after dilution into the commonly used flow cytometry buffer phosphate-buffered saline (PBS) and two other buffer solutions, Tris-HCl and M9 salts. These changes appeared very rapidly after dilution, and were linked to increased membrane permeability and loss in cell viability. We observed buffer-related effects in several different E. coli strains, K-12, C and W, but not E. coli B, which can be partially explained by differences in lipopolysaccharide (LPS) and outer membrane composition. Supplementing the buffers with divalent cations responsible for outer membrane stability, Mg2+ and Ca2+, preserved fluorescence signals, membrane integrity and viability of E. coli. Thus, stabilizing the bacterial outer membrane is essential for precise and unbiased measurements of fluorescence parameters using flow cytometry.}, author = {Tomasek, Kathrin and Bergmiller, Tobias and Guet, Calin C}, journal = {Journal of Biotechnology}, pages = {40 -- 52}, publisher = {Elsevier}, title = {{Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains}}, doi = {10.1016/j.jbiotec.2018.01.008}, volume = {268}, year = {2018}, } @article{82, abstract = {In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIRin these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”.}, author = {Chaudhry, Waqas and Pleska, Maros and Shah, Nilang and Weiss, Howard and Mccall, Ingrid and Meyer, Justin and Gupta, Animesh and Guet, Calin C and Levin, Bruce}, journal = {PLoS Biology}, number = {8}, publisher = {Public Library of Science}, title = {{Leaky resistance and the conditions for the existence of lytic bacteriophage}}, doi = {10.1371/journal.pbio.2005971}, volume = {16}, year = {2018}, } @misc{9810, author = {Chaudhry, Waqas and Pleska, Maros and Shah, Nilang and Weiss, Howard and Mccall, Ingrid and Meyer, Justin and Gupta, Animesh and Guet, Calin C and Levin, Bruce}, publisher = {Public Library of Science}, title = {{Numerical data used in figures}}, doi = {10.1371/journal.pbio.2005971.s008}, year = {2018}, } @article{457, abstract = {Temperate bacteriophages integrate in bacterial genomes as prophages and represent an important source of genetic variation for bacterial evolution, frequently transmitting fitness-augmenting genes such as toxins responsible for virulence of major pathogens. However, only a fraction of bacteriophage infections are lysogenic and lead to prophage acquisition, whereas the majority are lytic and kill the infected bacteria. Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity to bacteriophages are expected to act as a double-edged sword and increase the odds of survival at the cost of depriving bacteria of potentially beneficial prophages. We show that although restriction-modification systems as mechanisms of innate immunity prevent both lytic and lysogenic infections indiscriminately in individual bacteria, they increase the number of prophage-acquiring individuals at the population level. We find that this counterintuitive result is a consequence of phage-host population dynamics, in which restriction-modification systems delay infection onset until bacteria reach densities at which the probability of lysogeny increases. These results underscore the importance of population-level dynamics as a key factor modulating costs and benefits of immunity to temperate bacteriophages}, author = {Pleska, Maros and Lang, Moritz and Refardt, Dominik and Levin, Bruce and Guet, Calin C}, journal = {Nature Ecology and Evolution}, number = {2}, pages = {359 -- 366}, publisher = {Springer Nature}, title = {{Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity}}, doi = {10.1038/s41559-017-0424-z}, volume = {2}, year = {2018}, } @article{5984, abstract = {G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs.}, author = {Morri, Maurizio and Sanchez-Romero, Inmaculada and Tichy, Alexandra-Madelaine and Kainrath, Stephanie and Gerrard, Elliot J. and Hirschfeld, Priscila and Schwarz, Jan and Janovjak, Harald L}, issn = {2041-1723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Optical functionalization of human class A orphan G-protein-coupled receptors}}, doi = {10.1038/s41467-018-04342-1}, volume = {9}, year = {2018}, } @article{19, abstract = {Bacteria regulate genes to survive antibiotic stress, but regulation can be far from perfect. When regulation is not optimal, mutations that change gene expression can contribute to antibiotic resistance. It is not systematically understood to what extent natural gene regulation is or is not optimal for distinct antibiotics, and how changes in expression of specific genes quantitatively affect antibiotic resistance. Here we discover a simple quantitative relation between fitness, gene expression, and antibiotic potency, which rationalizes our observation that a multitude of genes and even innate antibiotic defense mechanisms have expression that is critically nonoptimal under antibiotic treatment. First, we developed a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression and knockout libraries, finding that resistance to a range of 31 antibiotics could result from changing expression of a large and functionally diverse set of genes, in a primarily but not exclusively drug-specific manner. Second, by synthetically controlling the expression of single-drug and multidrug resistance genes, we observed that their fitness-expression functions changed dramatically under antibiotic treatment in accordance with a log-sensitivity relation. Thus, because many genes are nonoptimally expressed under antibiotic treatment, many regulatory mutations can contribute to resistance by altering expression and by activating latent defenses.}, author = {Palmer, Adam and Chait, Remy P and Kishony, Roy}, issn = {0737-4038}, journal = {Molecular Biology and Evolution}, number = {11}, pages = {2669 -- 2684}, publisher = {Oxford University Press}, title = {{Nonoptimal gene expression creates latent potential for antibiotic resistance}}, doi = {10.1093/molbev/msy163}, volume = {35}, year = {2018}, } @article{438, abstract = {The MazF toxin sequence-specifically cleaves single-stranded RNA upon various stressful conditions, and it is activated as a part of the mazEF toxin–antitoxin module in Escherichia coli. Although autoregulation of mazEF expression through the MazE antitoxin-dependent transcriptional repression has been biochemically characterized, less is known about post-transcriptional autoregulation, as well as how both of these autoregulatory features affect growth of single cells during conditions that promote MazF production. Here, we demonstrate post-transcriptional autoregulation of mazF expression dynamics by MazF cleaving its own transcript. Single-cell analyses of bacterial populations during ectopic MazF production indicated that two-level autoregulation of mazEF expression influences cell-to-cell growth rate heterogeneity. The increase in growth rate heterogeneity is governed by the MazE antitoxin, and tuned by the MazF-dependent mazF mRNA cleavage. Also, both autoregulatory features grant rapid exit from the stress caused by mazF overexpression. Time-lapse microscopy revealed that MazF-mediated cleavage of mazF mRNA leads to increased temporal variability in length of individual cells during ectopic mazF overexpression, as explained by a stochastic model indicating that mazEF mRNA cleavage underlies temporal fluctuations in MazF levels during stress.}, author = {Nikolic, Nela and Bergmiller, Tobias and Vandervelde, Alexandra and Albanese, Tanino and Gelens, Lendert and Moll, Isabella}, journal = {Nucleic Acids Research}, number = {6}, pages = {2918--2931}, publisher = {Oxford University Press}, title = {{Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations}}, doi = {10.1093/nar/gky079}, volume = {46}, year = {2018}, } @misc{5569, abstract = {Nela Nikolic, Tobias Bergmiller, Alexandra Vandervelde, Tanino G. Albanese, Lendert Gelens, and Isabella Moll (2018) “Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations” Nucleic Acids Research, doi: 10.15479/AT:ISTA:74; microscopy experiments by Tobias Bergmiller; image and data analysis by Nela Nikolic.}, author = {Bergmiller, Tobias and Nikolic, Nela}, keywords = {microscopy, microfluidics}, publisher = {Institute of Science and Technology Austria}, title = {{Time-lapse microscopy data}}, doi = {10.15479/AT:ISTA:74}, year = {2018}, } @article{161, abstract = {Which properties of metabolic networks can be derived solely from stoichiometry? Predictive results have been obtained by flux balance analysis (FBA), by postulating that cells set metabolic fluxes to maximize growth rate. Here we consider a generalization of FBA to single-cell level using maximum entropy modeling, which we extend and test experimentally. Specifically, we define for Escherichia coli metabolism a flux distribution that yields the experimental growth rate: the model, containing FBA as a limit, provides a better match to measured fluxes and it makes a wide range of predictions: on flux variability, regulation, and correlations; on the relative importance of stoichiometry vs. optimization; on scaling relations for growth rate distributions. We validate the latter here with single-cell data at different sub-inhibitory antibiotic concentrations. The model quantifies growth optimization as emerging from the interplay of competitive dynamics in the population and regulation of metabolism at the level of single cells.}, author = {De Martino, Daniele and Mc, Andersson Anna and Bergmiller, Tobias and Guet, Calin C and Tkacik, Gasper}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Statistical mechanics for metabolic networks during steady state growth}}, doi = {10.1038/s41467-018-05417-9}, volume = {9}, year = {2018}, } @phdthesis{26, abstract = {Expression of genes is a fundamental molecular phenotype that is subject to evolution by different types of mutations. Both the rate and the effect of mutations may depend on the DNA sequence context of a particular gene or a particular promoter sequence. In this thesis I investigate the nature of this dependence using simple genetic systems in Escherichia coli. With these systems I explore the evolution of constitutive gene expression from random starting sequences at different loci on the chromosome and at different locations in sequence space. First, I dissect chromosomal neighborhood effects that underlie locus-dependent differences in the potential of a gene under selection to become more highly expressed. Next, I find that the effects of point mutations in promoter sequences are dependent on sequence context, and that an existing energy matrix model performs poorly in predicting relative expression of unrelated sequences. Finally, I show that a substantial fraction of random sequences contain functional promoters and I present an extended thermodynamic model that predicts promoter strength in full sequence space. Taken together, these results provide new insights and guides on how to integrate information on sequence context to improve our qualitative and quantitative understanding of bacterial gene expression, with implications for rapid evolution of drug resistance, de novo evolution of genes, and horizontal gene transfer.}, author = {Steinrück, Magdalena}, issn = {2663-337X}, pages = {109}, publisher = {Institute of Science and Technology Austria}, title = {{The influence of sequence context on the evolution of bacterial gene expression}}, doi = {10.15479/AT:ISTA:th1059}, year = {2018}, } @article{67, abstract = {Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution.}, author = {Igler, Claudia and Lagator, Mato and Tkacik, Gasper and Bollback, Jonathan P and Guet, Calin C}, journal = {Nature Ecology and Evolution}, number = {10}, pages = {1633 -- 1643}, publisher = {Nature Publishing Group}, title = {{Evolutionary potential of transcription factors for gene regulatory rewiring}}, doi = {10.1038/s41559-018-0651-y}, volume = {2}, year = {2018}, } @misc{5585, abstract = {Mean repression values and standard error of the mean are given for all operator mutant libraries.}, author = {Igler, Claudia and Lagator, Mato and Tkacik, Gasper and Bollback, Jonathan P and Guet, Calin C}, publisher = {Institute of Science and Technology Austria}, title = {{Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring}}, doi = {10.15479/AT:ISTA:108}, year = {2018}, } @article{538, abstract = {Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren. Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität während der Embryonalentwicklung. }, author = {Kainrath, Stephanie and Stadler, Manuela and Gschaider-Reichhart, Eva and Distel, Martin and Janovjak, Harald L}, journal = {Angewandte Chemie}, number = {16}, pages = {4679 -- 4682}, publisher = {Wiley}, title = {{Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen}}, doi = {10.1002/ange.201611998}, volume = {129}, year = {2017}, }