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Re: sukycospito post# 9816

Saturday, 07/24/2004 3:36:12 PM

Saturday, July 24, 2004 3:36:12 PM

Post# of 64738
SUKY copied this for people here to read. Great find btw. Not only does this put him in very good circles, it gives clues of yet another possible direction of CYGX.

Tatonkano

Worm yields cloning and cancer clues
Date: Thursday, January 10 @ 07:14:58 CET
Topic: Cancer


BOSTON, Jan. 9 (UPI) --
The first multicellular organism whose genome was fully identified has yielded a biochemical clue with implications for cloning and cancer research. Researchers working at Harvard Medical School and University of Massachusetts Cancer Center identified a key molecule in a worm that helps control what kind of organ or tissue an embryonic cell will become.


Although the molecule, called CBP-1, occurs in the tiny worm Caenorhabditis elegans, it is almost identical to the molecule that performs a similar function in humans, called p300. Yang Shi, an associate professor of pathology at Harvard Medical School and one of the lead researchers, told United Press International Wednesday he believes the findings apply to human molecular genetics. The scientists discovered how the CBP-1 molecule interacts with DNA in genes. The DNA is normally tightly wrapped around complexes of proteins called histones. Under this tightly wrapped condition, there is little room for other proteins that come in to turn the genes on or off.
The researchers discovered the CPB-1 molecule loosens the tightly wrapped DNA in the region of genes that control the fate of a cell. The loosening process involves adding small molecules called acetyl groups, to the DNA.

Previous work by Shi and colleague Dominica Calvo showed that if a specific gene was turned on in the worm the cell became intestine, but if the cell was left turned off it developed into muscle. If the gene is to be left turned off, that is, if the loosening process the researchers discovered is to be stopped, then the acetyl groups must be removed so the DNA can remain tightly wrapped. The scientists also found there are other molecules that come in and remove the acetyl groups, leaving the DNA tightly wrapped and resulting in the gene staying turned off.

"It's the balance between these two activities -- acetylation and deacetylation -- that will determine whether a gene is going to be on or off, and whether the cell will develop one way or another... "To do cloning in higher organisms, you have to understand how tissues form," Shi said. The human equivalent of the CBP-1 appears to be mutated in some human cancers. Shi's group believes the cancers may form because the acetylation process, which enables developmental genes to be turned on, is disrupted. Shi believes this can disrupt the developmental pathways and causes cells to grow into a cancerous mass. Shi believes such a process might be interrupted by restoring the acetylation process or by preventing the deacetylation process from occurring at all. Shi thinks small molecules might be introduced that could modulate the deacetylation process.

Researchers have known that acetylation and de-acetylation can effect gene expression, but this is the first detailed explanation of the specific mechanism. Some approaches to chemical treatment of leukemia are in trials and attempt to stop the deacetylation process.

Michael West, president of Advanced Cell Technology in Worcester, Mass., and part of the team that first cloned a human embryo, told UPI: "This phenomenon of cloning demonstrates the scientific fact that any cell in the body can be taken back in this little time machine we call the egg cell. "What we haven't known in the past is how the machinery of that egg cell works, how the egg cell can reprogram a cell, take it back in time like a time machine to an embryonic state such that it can then become many of the cells and tissue in the body," West said. He said Shi's research "puts one more piece of the puzzle in place and teaches us how some of that machinery works. Much remains to be determined." West said the goal is to translate gains in the laboratory into viable treatments for diseases, such as Parkinson's disease, diabetes, stoke and heart disease and to facilitate organ transplantation.

Malcolm Skolnick, chief executive officer of the biotechnology company CytoGenix in Houston and a former professor of biophysics, said the research was significant. If cells are going to be produced that can be used for therapeutic purposes, then ways will need to be developed to halt cell development or reverse it, Skolnick told UPI. "What we'd like to be able to is take stem cells back further toward totipotency, and (Shi's research) looks like it would help in that effort greatly," he said.

Totipotent cells are capable of forming every type of body cell. Any totipotent cell is capable of developing into a human being. In the human embryo, all cells are totipotent up until approximately the 16-cell stage. "It would be very useful if we fully understood this process and could take a differentiated cell and make it evolve back to pleuripotecy or even totipotency," Skolnick said.

Pluripotent cells are stem cells that eventually can develop into any type of body tissue, but do not have the capacity to form a human being. Skolnick believes the research will help lead to the understanding of the mechanisms that might allow pluripotent cells to be returned to totipotency. He acknowledged there might be many other reactions involved but said this particular mechanism appeared to be a key one.

(Reported by Joe Grossman in Santa Cruz, Calif.)



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