Examples of New Thinking in Biology
(Image of central dogma of biology and provided by User:Dhorspool [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons)
Two recent articles caught my eye because they reveal and reflect interesting possibilities arising from new scientific thinking about how to attack diseases. I’m not suggesting these thoughts will succeed as planned – who knows. But it does seem worth noting that new thinking is ongoing and may take society to places and products never before envisioned.
The first article refers to new thinking about trying to stop urinary tract infections by using a new non-antibiotic compound instead of antibiotics. UTIs may seem mundane but they can be a significant problem for some older persons, and indeed were part of the aging and Alzheimer’s disease process that ultimately killed my mother. According to a summary article from ScienceDaily:
"The scientists describe the development of anti-adhesion molecules that specifically interfere with the attachment of bacteria to human bladder cells. The most potent of the substances, an indolinylphenyl mannoside, prevented a UTI from developing in mice (stand-ins for humans in this kind of experiment) for more than eight hours. In the in vivo treatment study, a very low dose of 25 µg per mouse reduced the amount of bacteria in the bladder of the animals by almost 10,000 times, which is comparable to the standard antibiotic treatment with ciprofloxacin."
The second and more broadly profound article describes using epigenetics to "flip a switch" to activate previously silenced genes in fungus. Sounds boring, right? Maybe not so much when one reads on and learns about the valuable results obtained from fungi (think penicillin) and thinks about the potential power of epigenetic engineering and the broad swaths of the genome that hold secrets and mysteries not yet unraveled. Some text from the ScienceDaily summary is pasted below:
"Researchers at Oregon State University have discovered that one gene in a common fungus acts as a master regulator, and deleting it has opened access to a wealth of new compounds that have never before been studied — with the potential to identify new antibiotics.
The finding was announced today in the journal PLOS Genetics, in research supported by the National Institutes of Health and the American Cancer Society.
Scientists succeeded in flipping a genetic switch that had silenced more than 2,000 genes in this fungus, the cereal pathogen Fusarium graminearum. Until now this had kept it from producing novel compounds that may have useful properties, particularly for use in medicine but also perhaps in agriculture, industry, or biofuel production.
"About a third of the genome of many fungi has always been silent in the laboratory," said Michael Freitag, an associate professor of biochemistry and biophysics in the OSU College of Science. "Many fungi have antibacterial properties. It was no accident that penicillin was discovered from a fungus, and the genes for these compounds are usually in the silent regions of genomes.
"What we haven’t been able to do is turn on more of the genome of these fungi, see the full range of compounds that could be produced by expression of their genes," he said. "Our finding should open the door to the study of dozens of new compounds, and we’ll probably see some biochemistry we’ve never seen before."
The gene that was deleted in this case regulates the methylation of histones, the proteins around which DNA is wound, Freitag said. Creating a mutant without this gene allowed new expression, or overexpression of about 25 percent of the genome of this fungus, and the formation of many "secondary metabolites," the researchers found.
The gene that was deleted, kmt6, encodes a master regulator that affects the expression of hundreds of genetic pathways, researchers say. It’s been conserved through millions of years, in life forms as diverse as plants, fungi, fruit flies and humans.
The discovery of new antibiotics is of increasing importance, researchers say, as bacteria, parasites and fungi are becoming increasingly resistant to older drugs.
"Our studies will open the door to future precise ‘epigenetic engineering’ of gene clusters that generate bioactive compounds, e.g. putative mycotoxins, antibiotics and industrial feedstocks," the researchers wrote in the conclusion of their report."