Wednesday, April 28, 2010

Epigenetics: New or Just A Logical Understanding of Dynamic Systems

In a recent paper at the ASBMB conferences the authors state:

The new field of “epigenetics” is rapidly revealing how people, plants and animals do start with a certain genetic code at conception. But, the choice of which genes are “expressed,” or activated, is strongly affected by environmental influences. The expression of genes can change quite rapidly over time, they can be influenced by external factors, those changes can be passed along to offspring, and they can literally hold the key to life and death.

According to Rod Dashwood, a professor of environmental and molecular toxicology at the Linus Pauling Institute at Oregon State University, epigenetics is a unifying theory in which many health problems, ranging from cancer to cardiovascular disease and neurological disorders, can all be caused at least in part by altered “histone modifications,” and their effects on the reading of DNA in cells.

“We believe that many diseases which have aberrant gene expression at their root can be linked to how DNA is packaged, and the actions of enzymes such as histone deacetylases, or HDACs,” Dashwood said. “As recently as 10 years ago we knew almost nothing about HDAC dysregulation in cancer or other diseases, but it’s now one of the most promising areas of health-related research.”

Epigenetics is merely the extension of our understanding of genes. The understanding has progressed as follows:

1. Watson and Crick: DNA yields RNA yields Proteins. This prevailed for almost 20 years. It was a one way path that led to the ultimate protein yields result paradigm.

2. Reverse Transcriptase: This was the first step in understanding that we can have some feedback in the system.

3. Micro RNAs and the emergence of "noise" on the system.

4. Pathways: The understanding that there were complex pathways and that some of the resultant proteins could feed back and influence transcription.

5. Random hits on genes that changed base pairs or even split off sections. A good example is the Philadelphia chromosome in CML.

Now we must look at genes as a complex noisy multidimensional random process system. Genes are turned on and off by the results of other genes as well as the result of what receptors on the cell surface see in the environment. At the same time genes are changing if they get "hit" by exogenous factors such as radiation. Also as cells reproduce from generation to generation that process itself is subject to errors.

The result is that the cell is a random dynamic process of the form:

dx(t)/dt = f(x,t) + g(t) + w(t)

where f is the epigenetic factor, g some extracellular effects and w just noise, real uncertainty or just stuff we do not know.

What we observe is:

y(t) = h(x,t) + u(t)

where the ys may be the genes, RNA, proteins, all driven by what is the total underlying structure and u is again noise or uncertainty. This is epigenetics.

Our ability to do two things will be essential. First we must be able to determine this functions, namely observe and identify the system. Second we must learn how to control it. That leads to cures. Looking at the world in an epigenetic system manner is essential. That I see is often a challenge for scientists who are often still trying to understand the basic science.