METABOLIC OSCILLATIONS: Cellular decision-making

For this post as part of the “Metabolic oscillations” series, Josi Buerger introduces us to the publications that inspired the creation of this ITN network. The series will focus on the underlying concepts, explain the four main publications stretching from 2010 to 2016, and lay out how the Fellows’ efforts will push this work forward into 2017.

Regulation is at the heart of the cell

Within the cell, genes and proteins are regulated. There are two reasons for this: firstly, a cell can respond to its environment by changing or regulating its internal state. Secondly, it is much more cost-effective if this change happens by modulating existing structures instead of tearing everything down and creating it from scratch. Consider how much less effort it is to dim the lights in the evening as opposed to dismantling the electrical circuits and then reconstruct them in the morning…

The ability to regulate internal states is the basic concept of the first publication featured as part of our “Metabolic oscillations” series, Bacterial adaptation through distributed sensing of metabolic fluxes.  In today’s post we’ll discuss the basic concept of cells responding to their environment and use a textbook example: carbon source utilization. Or, in more laymen’s terms: cells have food preferences.

Cells have food preferences.

Weird, isn’t it? But Escherichia coli’s sweet tooth is one of the cornerstone experiments in the field of microbiology dating back to 1957 (Cohen & Monod). Also there is a link between preferring one type of food and changing cellular metabolism to suit the preference. For example, E. coli loves glucose (a type of sugar). When glucose passes through the outer membrane of the cell, it activates a number of other processes which all help the cell to preferentially eat the glucose.

carbon-ut-jpg

You can see this in the image on the right: the blue line indicates E. coli cell growth in an environment where both glucose and acetate is available. The total amount of glucose is indicated by the dotted line, which decreases as the cells consume it to grow. Once all the glucose is consumed, the cells are forced to switch to acetate, indicated by the drawn-through line (Image modified from Kotte et al., 2010).

How to sense acetate?

So far, so good.  Yet as always in biology, the picture becomes more complicated as soon as you zoom in on the details.

For glucose, there is an elegant link between transport and regulation. But even though cellular behaviour to acetate is well-documented, it is unknown how cells detect acetate. Generally, there are two main detection systems: membrane-based sensing as with glucose, or transcription-factor based sensing where the molecule is recognised by a specific sensing modules. Neither system has been found for acetate, despite decades of interest.

Here’s the cool bit about Bacterial adaptation through distributed sensing of metabolic fluxes.  The researchers show that the preference of glucose to acetate can be explained by elements of the cell that we already know about. There isn’t some undiscovered acetate sensing system, but rather the elements of the cell can behave in more ways than we thought!

The details? Well, you will just have to wait for our next post…..

 

References

Kotte, Oliver, Judith B. Zaugg, and Matthias Heinemann. “Bacterial adaptation through distributed sensing of metabolic fluxes.” Molecular systems biology 6.1 (2010): 355.

 

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SERIES INTRODUCTION: The ups and downs of metabolism

New year, new series on the metaRNA blog!

For the upcoming posts on “Metabolic oscillations”, Josi Buerger introduces us to the publications that inspired the creation of this ITN network. The series will focus on the underlying concepts, explain the four main publications stretching from 2010 to 2016, and lay out how the Fellows’ efforts will push this work forward into 2017.

 

Life isn’t static. It can’t be – in biological systems, stagnation means death.

Even though cells are rules by homeostasis, this continuous fine-tuning of cellular processes is anything but static.

Homeostasis: Self-regulation to maintain internal equilibrium.

For example, the human body strives to maintain 37 °C as its internal temperature via heat-loss (sweating) or heat retention (goose-bumps).

But remember, the cell itself cannot think or make decision like our human minds. Individual cells don’t have a brain that acts as the central decision maker. Some argue that cellular fate is encoded in its DNA and this should be seen as a “brain” of sorts. However, the cell must still be able to respond to external events or internal catastrophes above and beyond the determination of the DNA code.

So how is this possible? What kind of situation requires immediate and total cellular responses? And what does this response look like?
introduction

The following four papers have been chosen as the features of our new series to answer these questions:

  1. Bacterial adaptation through distributed sensing of metabolic fluxes
  2. Functioning of a metabolic flux sensor in Escherichia coli
  3. Phenotypic bistability in Escherichia coli’s central carbon metabolism
  4. Autonomous metabolic oscillations robustly gate the early and late cell cycle

Join in as we explore cellular decision-making!