University of Wisconsin-Madison

June 19, 2006

E. Coli Research Identifies Two New Keys To Regulation Of Bacterial Gene Expression

The cellular process of transcription, in which the enzyme RNA polymerase constructs chains of RNA from information contained in DNA, depends upon previously underappreciated sections of both the DNA promoter region and RNA polymerase, according to work done with the bacterium E. coli and published today (June 16) in the journal Cell by a team of bacteriologists from the University of Wisconsin-Madison.

This fundamental research about a key step in RNA synthesis has important implications for the study of gene expression in other organisms, and adds to the wealth of knowledge about E. coli contributed by scientists from the UW-Madison.

"The kinds of processes that we study in E. coli happen in a wide variety of bacteria of medical, environmental and agricultural importance," notes Rick Gourse, a professor of bacteriology who published the Cell paper along with a team from his lab. "This knowledge can ultimately be put to use in systems that aren't so amenable to investigation, such as bacteria that cause cholera, produce anthrax toxin or lead to ulcers and stomach cancer."

Scientists use model organisms because they are relatively easy to work with and because there is a vast amount of previous knowledge about them. They can then test whether their findings in model organisms hold true in other species, says Gourse, who studies a strain of E. coli that while harmless, is closely related to disease-causing varieties like E. coli 0157:H7.

"Basic research in E. coli is very important," says Gourse. "Much of what we know about gene expression both in bacteria and in higher life forms comes from work performed originally on this model organism." The strain that Gourse works with is one of the most well-studied species in biology and has important ties to the UW-Madison. In his most recent study, Gourse investigated the interaction between RNA polymerase and promoters from the E. coli chromosome. RNA polymerase reads the information in DNA and transcribes it into chains of RNA, which are later translated into proteins. Promoter regions are specific sequences within the DNA chain that tell RNA polymerase when and where to begin transcription, and how much product to make from specific genes.

Gourse's group found that there is a specific region within DNA promoters that makes contact with a highly conserved but previously underappreciated segment of the sigma subunit of RNA polymerase. While the contact with sigma is very strong at promoters for most genes, it is particularly weak at promoters that make ribosomal RNA, which means that other factors like nutritional and environmental signals ultimately regulate the expression of those genes.

"In this case, regulation is achieved not because the promoter makes a special contact, but because it can't establish contact at all," says Gourse. "This is an example of how sometimes less is more, and a probably very ancient example of one of the methods that arose through evolution to regulate gene expression."

Ribosomal RNA makes up the bulk of ribosomes, the molecular machines that make proteins and are present in huge numbers in all cells. Since so much of the cell's energy is used to make ribosomes, control of ribosomal RNA transcription is particularly crucial to a cell's well-being.

"This work is basic to the growth of all bacteria," says Gourse. "By understanding transcription and control of ribosome synthesis in E. coli, we can understand more about these processes in bacterial species that we need to control, like those that cause disease or make toxins. E. coli is also the workhorse of the biotechnology industry. Understanding E. coli gene expression in detail allows us to harness these cells for producing products of biotechnological importance, like pharmaceuticals."

Source: http://www.sciencedaily.com/releases/2006/06/060618223905.htm

As is quite common, the report concludes with a vague promise of great "breakthrough medicines" to come in the near future (if the researchers continue to get their funding, of course). And yet the researchers make the explicit point that nutritional and environmental factors appear to be paramount, and certainly not the "genetic code" by itself. Another point is how a "model" is created from what is observed in one species of bacteria, and from that all kinds of assumptions are made, which of course all too often find their way into textbooks, appearing as "absolute fact" to many students (and teachers as well). It's worth mentioning that with "HIV/AIDS," a model was generated from clinical observations, and not from cellular-level or molecular-level ones. Then, shared "markers" that were thought to be consistent with this model were sought, and some were found, though only in some patients. Attempts at determining underlying mechanisms were undertaken, and all have failed, though the technology is available to do so - thus it is basically one big pile of assumptions and models. And yet even models that were demonstrated to be incorrect are still being touted as "what happens" when a person is "HIV infected." Before the clinical observations, there was speculation about various phenomena that came to be deemed an "infection" by a "retrovirus," but nothing beyond this hazy, presumptuous sheen of technical "knowledge." At a loss for a truly scientific explanation, the "bug hunters," who were in charge of things, decided to force the square pegs into round holes.

If you'd like to get a sense of how little evidence there is of "HIV," go to this link, which discusses what a recent attempt at "isolation" actually revealed:

http://theperthgroup.com/REJECTED/StructureLetterPG.pdf

They (the Perth Group) are responding to a particular study. One media report of it contains the following:

QUOTE: [Professor Stephen Fuller said] "You say can you show me the structure of the HIV virus and the question is which one.

"HIV is very variable. It varied in diameter by a factor of three."

The way the research team, from the Wellcome Trust Centre for Human Genetics at Oxford University, dealt with this was by taking multiple images at different tilts.

Working with colleagues in Heidelberg and Munich, they took about 100 images of 70 individual HIV viruses and then looked at similarities.

Despite the variability, the team found some consistent features... This included the finding that the core of virus - which is cone-shaped - spans the width of the viral membrane. But there are spikes on the outside which bind to human immune cells, called T cells, and allow the virus to invade them. UNQUOTE.

Exactly how this can pass as "isolation" is beyond comprehension, though one has to give some credit to Fuller, who is reporting his findings accurately (though he assumes that "HIV" must be there, somewhere). Another thing that makes no sense is that there is no explanation about how the "virus" "invades" cells. A virus needs to be activated before it does anything, remaining inert until the proper signals are received, and thus this statement about binding and invading is at the very least incomplete. Of course, even if we decided to accept this assumption (with no evidence to support it), there should still be ample evidence of "HIV" killing off these cells, and no such evidence exists to date. The cells sometimes, but not always, tend to decrease in those said to be afflicted with "AIDS" over time, and so it is assumed that "HIV" is the cause of this (though again, not all "AIDS deaths" are due to this loss of cells anway).

Source of this report: http://newsvote.bbc.co.uk/mpapps/pagetools/print/news.bbc.co.uk/2/hi/health/4642940.stm