Reading the Cellular Instruction Manual

January 17, 2014

Guest post By David Knox

It is much easier to use a machine if you can read the manual. But being a typical male I can understand the need to ignore the manual and just play with the knobs and buttons to see what they do.

Molecular biology experiments are doing just that. They isolate a single complex or molecule and play with it, changing its concentration or changing the structure of the molecule and measuring the differences that occur in the cell. By systematically ‘playing with’ each molecule’s knobs and buttons, we have explored how those individual molecules changes the behavior of the system.

DNA

Using this knowledge we try to change the behavior of the cells that are not behaving correctly by drugs that change the active concentrations of molecules or inhibit the cell from making the wrong molecules. We try turning the knobs in order to make the cell more normal. But often we are only looking a what is happening at one place in the cell. Every action within this complex system has many effects everywhere in the cell.

The instruction manual for a cell’s behavior is encoded into the DNA. The problem is that we still don’t know how to read it. We know that some of the molecules in the cells can bind with the DNA and change the behavior by producing more (or less) of a protein. The process of converting the DNA into proteins can be broken down into simple steps: DNA is copied into RNA by a process called transcription; the RNA is used as the working blueprint from which many proteins can be built by a process called translation.

DNA is transcribed into RNA which is translated into Proteins.

The statement above is the central doctrine of biology. The statement should be extended to be circular, because the creation of proteins has an effect on which DNA is transcribed. The cell is in a constant state of flux and the system responds to changes in the external environment or within the cell. The system has many feedback loops creating checks and balances to keep the production of proteins within acceptable ranges.

The DNA is very long manual with contingencies for many different functions, some only during development of the organism, some only activated when the cell needs to divide, and some are only activated when the cell needs to die. Within the entire genome (all the DNA), only a small portion represents the blueprints for producing proteins and these segments are called genes. Some of the other DNA is used to directly control the transcription of the genes, but much of the DNA’s purpose is still unknown.

Mountain View

The proteins that bind to the DNA, collectively called DNA binding factors, can actually read the sequence of DNA and bind in specific positions to control the transcription activity around that position. The DNA encodes the signals of where these molecules bind and molecular biologist have discovered many of the signals used by each individual factor. But, many of these signals are overlapping with in the DNA sequence, which forces the individual factors to compete for binding to the DNA. This competition permits the cellular environment to dictate different binding of proteins depending on the local environment’s concentration of proteins. For example, a low level of a protein in the cell does not activate the production of a gene, but once the concentration reaches a certain level that allows it to out-compete other factors and transcription is initiated. There could also be a feedback loop that causes the cell to stop production when the concentration increases to a level that causes the protein to out-compete in a region that blocks or inhibits transcription. Controlling the production of genes is known as Transcriptional Regulation.

We are only beginning to understand the complex balance of different mechanisms used in the cell to regulate the transcription. As we begin to understand the individual mechanisms down their behavior at individual nucleotides of DNA, we begin to see the small effects that changes in concentration of a factor can have on the system as a whole. It is this complex system of small and sometimes subtle shifts in factors bound to the DNA on which my research if focused. I am creating a model of these DNA buttons and knobs based on our current knowledge of each factors behavior in the attempt to understand some of the signal embedded into the DNA. And maybe someday soon we will begin to understand how to read the manual and begin learning what is written in our DNA.

This article is syndicated from the author’s own blog, Visualizing Biological Processes.

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