Dynamics in Transcriptional Networks

9/18/2018

Outline

1. Central Dogma of Molecular Biology

2. Biological networks

3. Motifs in the E. coli transcriptional network

- 1-node transcriptional motifs

- Simple gene regulation

- Autoregulation

Optional Reading and References

  • An Introduction to Systems Biology: Design Principles of Biological Networks; Chapters 1-3
  • Savageau, Biochemical Systems Analysis. A study of function and design in molecular biology, Biochemistry and Molecular Biology Education, 1976
  • Thieffry et al., From specific gene regulation to genome networks: a global analysis of transcriptional regulation in Eschericia coli, BioEssays, 1998
  • Becskei and Serrano, Engineering stability in gene networks by autoregulation, Nature, 2000
  • Shen-Orr et al., Network motifs in the transcriptional regulation network of Escherichia coli, Nature Genetics, 2002
  • Rosenfeld et al., Negative autoregulation speeds up the response times of transcription networks, Journal of Molecular Biology, 2002
  • Lee Megeney, The yeast kinome displays scale free topology with functional hub clusters, BMC Bioinformatics, 2005
  • Berger et al., Compact, universal DNA microarrays to comprehensively determine transcription-factor binding site specificities, Nature Biotechnology, 2006
  • Miller et al., Sequencing the nuclear genome of the extinct wooly mammoth, Nature, 2008
  • Brückner et al., Yeast two-hybrid, a powerful tool for systems biology, International Journal of Molecular Sciences, 2009
  • Baryshnikova et al., Quantitative analysis of fitness and genetic interactions in yeast on a genome scale, Nature Methods, 2010
  • Reece-Hoyes et al., Enhanced yeast one-hybrid assays for high-throughput gene-centered regulatory network mapping, Nature Methods, 2011
  • Costanzo et al., A global genetic interaction network maps a wiring diagram of cellular function, Science, 2016

Slides

9/20/2018

Outline

1. Review (1-node motifs)

Simple gene regulation

Negative autoregulation (NAR)

Positive autoregulation (PAR)

2. Families of network motifs in E. coli

3-node Feed-forward loops

4+ node motifs

Optional Reading and References

  • An Introduction to Systems Biology: Design Principles of Biological Networks; Selections from Chapters 4-6
  • Mangan et al., The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks, Journal of Molecular Biology, 2003
  • Kalir et al., A coherent feed-forward loop with a SUM input function prolongs flagella expression in Escherichia coli, Molecular Systems Biology, 2005
  • Uri Alon, Network Motifs: theory and experimental approaches, Nature Reviews Genetics, 2007

Notes

Slides

9/25/2018

Outline

1. Review

Diversity & robustness

Network motifs and dynamics

2. Perception

Psychophysics

Cellular perception

3. Heterogeneity and dynamics in single cells

Nuclear localization of NFkB encodes transcriptional signals

Fold change detection

NFkB redux

(supplement) Dynamics in other signaling systems

Optional Reading and References

  • Milo et al. Network Motifs: Simple building blocks of complex networks, Science, 2002
  • Goentoro et al. The incoherent Feedforward Loop Can Provide Fold-Change Detection in Gene Regulation, Molecular Cell, 2009
  • Shoval et al. Fold-change detection and scalar symmetry of sensory input fields, PNAS, 2010
  • Purvis, et al. p53 Dynamics Control Cell Fate, Science, 2012
  • Purvis, and Lahav. Encoding and Decoding Cellular Information through Signaling Dynamics, Cell, 2013
  • Lee, et al. Fold change of nuclear NF-κB determines TNF-induced transcription in single cells, Molecular Cell, 2014
  • Ryu et al. Frequency modulation of ERK activation dynamics rewires cell fate, Molecular Systems Biology, 2015
  • Adler et al. Optimal regulatory circuit topologies for fold-change detection, Cell Systems, 2017

Notes

Slides