Monday, 2 June 2014

Brian David Strahl a licensed chromatin biologist


Dr. Brian David Strahl a licensed chromatin biologist at the University of North Carolina. Together with his group, they have been in the forefront of discovering how small how small chemical additions or molecular “tags” on histone proteins balance the accessibility of DNA and the genetic information it contains. Histones are central point to the organization of our DNA in cells.  These proteins come in different types or isoforms such as H3, H4, H2A and H2B, and they link with themselves as a means to package our DNA within the small nuclei of cells. Two copies each of each histone type come together to create what is called an octamer, which wraps about 147 base pairs of DNA around it.  This structure (histones + DNA) makes up the basic building block of chromatin which is called the nucleosome. The strings of nucleosomes develop the chromatin fiber and they systematize into higher-order structures that are poorly determined but allow large genomes(e.g., ~3.4 billion base pairs making up the human genome) to fit in the confines of a 2-10 micron nucleus.  This extraordinary level of compaction is further interfered by the actions of a 5th histone type known as linker histone H1.

 
Brian Strahl


With all his compaction, the number question is how our genome is made accessible at the right place and time for all of the essential processes that happens with DNA (such as gene expression, DNA repair and replicating the genome).  As it turns out, histones, and the nucleosomes they form, are the major administrators of chromatin compaction and decompaction. Just about every process needs protein machineries that bind it.  Each of these machineries is highly tuned to collaborate with, and control, the histones that wrap DNA. 

Brian Strahl professor

 

Huge mechanisms by which histones are controlled to alter the accessibility of DNA are the chemical modifications or molecular “tags” that are placed on them. Many enzymes have been classified over the last few decades that add (i.e., write) or eliminate (i.e., erase) these histone modifications. The chemical tags serve as signals or messages to inform chromatin how to act whether to have open or close, and/or express a gene or not. The question of how these chemical tags work have been at the core of many researches and studies. Some shows that the histone modifications either act in a physically manner to change nucleosome solidity or nucleosome-nucleosome interactions, or by recruiting “effector” proteins that then carry out the biological function. A huge number of histone modifications have been examined, which happen on each histone type. Moreover, many effect proteins making use specialized domains have been found to read these histone marks. While much has been known in the area of histone function, a great deal more work is needed to figure out how histone modifications impact chromatin structure and function.  This very critical as recent and past studies is discovering that many human mutations that are linked with diseases such as cancer happen in the histones themselves or the protein machineries that are ramified in histone/DNA regulation.  In his lad, he determine how the protein machineries that handle histones are employed to chromatin, how histone modifications become protected and safe, and then how these modifications are read or interpreted to advance chromatin function.