@article{6717,
  abstract     = {With the recent publication by Silpe and Bassler (2019), considering phage detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many as five examples of phage-associated intercellular communication (Table 1). Each potentially involves ecological inferences by phages as to concentrations of surrounding phage-infected or uninfected bacteria. While the utility of phage detection of bacterial QS molecules may at first glance appear to be straightforward, we suggest in this commentary that the underlying ecological explanation is unlikely to be simple.},
  author       = {Igler, Claudia and Abedon, Stephen T.},
  journal      = {Frontiers in Microbiology},
  publisher    = {Frontiers},
  title        = {{Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision}},
  doi          = {10.3389/fmicb.2019.01171},
  volume       = {10},
  year         = {2019},
}

@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},
}

@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{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},
}