@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},
}

@misc{5556,
  abstract     = {MATLAB code and processed datasets available for reproducing the results in: 
Lukačišin, M.*, Landon, M.*, Jajoo, R*. (2016) Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast.
*equal contributions},
  author       = {Lukacisin, Martin and Landon, Matthieu and Jajoo, Rishi},
  keywords     = {transcription, pausing, backtracking, polymerase, RNA, NET-seq, nucleosome, basepairing},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{MATLAB analysis code for 'Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast'}},
  doi          = {10.15479/AT:ISTA:45},
  year         = {2016},
}

@article{6161,
  abstract     = {The tra-1 gene is a terminal regulator of somatic sex in Caenorhabditis elegans: high tra-1 activity elicits female development, low tra-1 activity elicits male development. To investigate the function and evolution of tra- 1, we examined the tra-1 gene from the closely related nematode C. briggsae. Ce-tra-1 and Cb-tra-1 are unusually divergent. Each gene generates two transcripts, but only one of these is present in both species. This common transcript encodes TRA-1A, which shows only 44% amino acid identity between the species, a figure much lower than that for previously compared genes. A Cb-tra-1 transgene rescues many tissues of tra-1(null) mutants of C. elegans but not the somatic gonad or germ line. This transgene also causes nongonadal feminization of XO animals, indicating incorrect sexual regulation. Alignment of Ce-TRA-1A and Cb-TRA-1A defined several conserved regions likely to be important for tra-1 function. The phenotype differences between Ce-tra- 1(null) mutants rescued by Cb-tra-1 transgenes and wild-type C. elegans indicate significant divergence of regulatory regions. These molecular and functional studies suggest that evolution of sex determination in nematodes is rapid and genetically complex.},
  author       = {de Bono, Mario and Hodgkin, J.},
  issn         = {00166731},
  journal      = {Genetics},
  keywords     = {amino acid sequence, article, caenorhabditis elegans, evolution, genetic variability, nonhuman, priority journal, sex determination, Amino Acid Sequence, Animals, Animals, Genetically Modified, Base Sequence, Caenorhabditis, Caenorhabditis elegans, Caenorhabditis elegans Proteins, DNA, Helminth, DNA-Binding Proteins, Evolution, Molecular, Female, Helminth Proteins, Membrane Proteins, Molecular Sequence Data, Mutagenesis, RNA, Messenger, Sequence Homology, Amino Acid, Sex Determination (Analysis), Transcription Factors, Transgenes, Turner Syndrome, Animalia, Caenorhabditis, Caenorhabditis briggsae, Caenorhabditis elegans, Nematoda},
  number       = {2},
  pages        = {587--595},
  publisher    = {Genetics Society of America},
  title        = {{Evolution of sex determination in Caenorhabditis: Unusually high divergence of tra-1 and its functional consequences}},
  volume       = {144},
  year         = {1996},
}