Ruprecht Karls Universität Heidelberg


Noise in biochemical networks

This seminar is offered to master students in physics and related disciplines who are interested in recent advances in quantitative biology, in particular the application of stochastic dynamics to biological systems. The seminar is jointly run by Thorsten Erdmann and Ulrich Schwarz and takes place Wednesday from 11.15 to 12.45 in one of the seminar rooms in the Bioquant building. The first meeting was on October 12. Each contribution should be in English, with up to 45 minutes of presentation and 15 minutes of discussion. To get six credit points for the master studies (MVSem), an additional written report is required.

During the last decade, stochastic fluctuations (in short, noise) have emerged as a central element of the way biological systems function. Noise is not only unavoidable in molecular systems, it can also be exploited by cells to increase systems performance, for example in gene expression, signaling, development, differentiation and evolution. Recent advances in single cell analysis are complemented by new theoretical models and together reveal a new dimension of biological systems. In this seminar, we will discuss recent advances in our quantitative understanding of how noise shapes cellular decision making.

The seminar will start with an introduction into the fundamental role of biochemical networks in cells as control systems for various decision making processes. We will discuss some of the best studied model systems for biochemical networks. Next we turn to the long known observation of large cell-to-cell variability and how this recently has been measured in large quantitative detail for single cells (both bacteria and eukaryotes). Because only 1-2 copies of a gene exist in a given cell, gene expression is the noisest element in cells and we discuss the quantitative details. We then go up in scale, to genetic switches and larger networks and organisms. Finally we discuss the physiological role of noise in general, and competing mechanisms for heterogeneity.

The following subjects are suggested for presentations.

Biochemical networks

  • Motifs in biological networks (Tyson, Arkin)
  • Lac operon (Vilar and Leibler)
  • Lambda switch
  • Bacterial chemotaxis (Barkai, Alon, Leibler)
  • Oscillations in biological systems

Cell-to-cell variability

  • Non-genetic variability (Spudich and Koshland)
  • Single-cell analysis (Elowitz, Oudenaarden)

Noise in gene expression

  • Stochastic mechanisms in gene expression (translation, transcription, bursts, cascades, copy numbers)
  • Extrinsic versus intrinsic noise (Elowitz, Swain, Siggia, Hilfinger, Paulsson)
  • Genetic switches (lambda switch and toggle switches; Arkin, Warren and ten Wolde)
  • Noise propagation and regulation in genetic networks (Oudenaarden)

Noise in larger networks

  • Bacterial chemotaxis (Kollmann)
  • Circadian rhythms (Barkai, Kollmann)
  • Noise in morphogen gradients (ten Wolde, Howard)

State switching and differentiation

  • Antibiotic persisters (Balaban, Kusell)
  • Stem cells and cancer (Simons)
  • Apoptosis (Sorger)
  • Sporulation in B. subtilis (Bischofs)

Cost and benefits of noise

  • Physiological role of noise (Arkin, Oudenaarden, Elowitz)

Competing mechanisms for heterogeneity

  • micro-environmental niches (Snijder, Pelkmans)
  • genetic heterogeneity

PDFs

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