STEM CELL RESEARCH

Contributions from Roger Kornberg

(Roger and Arthur Kornberg. Both Nobel prize winners)

Stem cells are derived from proliferating embryos. The cells are pluripotent and are becoming a new wave front of study in medicine, genetics and many other fields of the biological sciences. Cells with the ability to become any tissue or express any gene or trait that one may desire to activate in a stem cell are quite useful in understanding how and why certain cells become a certain tissue. Understanding how the genes, DNA to RNA to protein, that make the specific proteins for each class of cells until recently wasn’t clear. Roger Kornberg’s work in and around the method of transcription in prokaryotes and foremost eukaryotic cells has earned him the 2006 Nobel prize in chemistry.

He has successfully given the scientific community the structure and molecular function of eukaryotic RNA polymerase2 transcription enzyme. Compared to the prokaryotic system, eukaryotes have an array of transcription factors that regulate and activate this remarkable enzyme according to the gene and or transcript desired by the cell itself, which is completely controlled by chemical signals through self stimulation or external stimulus activating the transcription pathway of the desired gene. Remembering that the goal of transcription is to make a protein product from the RNA that is synthesized from DNA we can begin to start utilizing this new understanding of the process that cells have for making DNA into RNA into protein studies can move deeper into the realm of the stem cell. 

 In the past we have been able to successfully integrate DNA into cells, mammalian and bacterial, to produce the desired, normal or mutated, gene product in order to look at expression and the affects of the gene product produced. We have overlooked the details of that simple process because we understood the central dogma of biochemistry. Now that technology is available to isolate, purify and make interactive 3D models of the proteins, a new force has began to emerge, stem cells, and the need for further insight is needed. Stem cell study has given us the ability to generate cloned sheep, mice carrying various human and or genes of interest, vegetables that have a longer shelf life, rice that is more nutritious and ideas into solving medical questions only years ago we ever knew existed. Understanding of how to control the genes that are either wanted or unwanted in a study is essential in the quest for knowledge. In 1999, Tudor et al., presented a look at a co-activator of RNAP, Srb7 in embryonic mouse cells. Conclusions brought value to this protein in that disruption of the gene in stem cells flirts with vitality and cell development. They also concluded that murine Srb7 associates exclusively with high molecular weight RNA polymerase proteins and are present in almost every tissue that has essential roles in gene expression in the body. Taking normal and induced mutated Srb7 genes from human and mouse cDNA libraries they looked at the regulation of Srb7 transcription in these cells to look at viability and essential function of these cells in growing mouse embryos. Studies like these, even though before Kornberg’s work were finished, show the necessity to understand the function and mechanisms of the transcription process.

 In 2003 Zhou et al. comments about how the linking of two broad fields the “control of gene expression” and “stem cell biology” have started integrating. Addressing the mechanisms on activation and regulation of transcription and insight into the needed incorporation of developmental and therapeutic applications. Further insight into understanding our own bodies has lead to research dealing with the product of transcription, RNA. Viral infections have been infecting humans… well, since the invention of the human. Recent studies have shown that lower organisms implement a type of viral DNA interfering RNA, i RNA, as a defense mechanism. The single stranded RNA binds to the viral DNA in a sense interfering with the transcription of the incorporated viral DNA. Erica Check writes about this new found study in [Erica Check “Gene regulation: RNA to the rescue?” Nature 425, 10-12 (4 September 2003).] The up and coming goal is to try this  iRNA method in mammalian models that have been infected by viral DNA. Researchers believe that these i RNA’s may have the ability to cure any genetic problem and viruses like HIV are first on the list for study.

Just like the first time an early human looked in a pond and “saw” his own image and pondered, we too have yet to see and understand our selves as a molecular machine. Working out the colossal molecular structure and function of the seemingly simple process of transcription gives us another small step for man and one hopeful giant leap for mankind.