“A man speaking sense to himself is no madder than a man speaking nonsense not to himself.” 

19 January, 2015

Yehoshua Gefen

- Tom Stoppard

“Secreting and Sensing the Same Molecule Allows Cells to Achieve Versatile Social Behaviors.”

• Aims– To build a mathematical model which explains the  versatility of the secrete-and-sense motif.

– To explain the recurrence of the secrete-and-sense self-signaling motif across species.“The advantages of using secrete-and-sense circuits have been unclear in many situations. For example, if a cell’s primary purpose is self-communication, then it is unclear why the cell secretes molecules instead of relying entirely on intracellular signaling.” (1)

Science 343 (2014), H. Youk, W. A. Lim 

Definitions• Synthetic biology: an interdisciplinary branch of biology, designing and constructing biological devices and systems for useful (?) purposes.

• System biology: an interdisciplinary field of study that focuses on complex interactions within biological systems using a holistic approach and engineering principles to biological and biomedical research.

• Quorum sensing: a system of stimulus and response correlated to population density.

Introduction: SECRETE AND SENSE

Engineered Secrete-and-Sense Circuit Motif

A synthetic system which does not explain the true

nature of its original model.

Flow Cytometer

Assay 1: Secretion Rate and Receptor Abundance

No proof was delivered for the localization of the α factor – receptor reaction on the extracellular side of the membrane.

Extrapolation?

Assay 2: Positive Feedback linking Sensing with Secretion

 

Some inconsistent data was delivered in the supp.

Assay 3: Positive Feedback with Signal Degradation

Periplasmic Space

Discussion: Mathematical Model (translation knowledge from synthetic to natural systems)

Their Conclusions

• Self-communication competes with neighbor communication because they both use the same molecule and receptor.

• The differences between local high concentration of alpha factor and global concentration of alpha factor determines the behavior of secrete-and-sense circuit motif.

• Population and individual behavior can be defined by models of reaction in unison, bimodal activation, and positive feedback versus signal degradation dynamics.

My Discussion Points

• The problem of translating a mathematical model or simulation from a synthetic approach to a biological one.

• A holistic approach should be accompanied by an attention to the specifics (e.g. localization of receptor signal, diffusion rate and distances, and the question of evolution).

• They did not explain why the chose these concentrations and these time frames.

Thank You!