View Full Version : Multiple Cellular Codes
07-12-2007, 05:47 PM
Turns out we are not only governed by the DNA code, but two other codes as well.
The 3 codes:
The ribosomal code
The Histone code
And of course the DNA code
Multiple Cellular Codes (http://www.weekinscience.com/node/70)
28-12-2007, 07:12 PM
New plant study reveals a 'deeply hidden' layer of the transcriptome: (http://www.eurekalert.org/pub_releases/2007-12/si-nps122107.php)
Since the common notion is that the exosome plays a central role in bulk RNA turnover, the researchers say, they expected to find the levels of all transcripts increasing when they inactivated the exosome complex. “But not everything is going up, instead the exosome mechanism seems to be very tightly regulated,” says Ecker. “We didn’t see regions that are known to be silenced to go up, instead we found a very specific group of transcripts that are regulated in this way.”
Among them are regular protein-coding RNAs, RNA processing intermediates and hundreds of non-coding RNAs, the vast majority of which hadn’t been described before. “These strange transcripts are associated with small RNA-producing loci as well as with repetitive sequence elements,” says Gregory. “They are under very tight regulation by the exosome, but we still don’t know exactly what this means.”
“It is likely that these RNAs that are usually ‘deeply hidden’ become important for genome function or stability under some circumstances”, adds co-first author Julia Chekanova, an assistant at the University of Missouri-Kansas City. “We need to do more work to figure out what these circumstances are.”
23-04-2008, 07:33 PM
1) Mechanism Of Epigenetic Inheritance Clarified (http://www.sciencedaily.com/releases/2008/04/080422151826.htm)
Slowly unraveling the mysteries of phenotypic plasticity and how the same genome can give rise to different phenotypes.
2) Insight into the importance of epigenetic factors in evolution will help understand what caused this:
Lizards Undergo Rapid Evolution After Introduction To A New Home. (http://www.sciencedaily.com/releases/2008/04/080422151826.htm)
Unanswered questions of these lizards.
How much is due to random mutation and natural selection?
How much was gene expression affected by random mutation, and how much was gene expression altered by epigenetic factors?
How big a role does the histone code play during evolution?
3) Front-loading sight, smell and hearing?
Sea Urchins' Genetics Add To Knowledge Of Cancer, Alzheimer's And Infertility (http://www.sciencedaily.com/videos/2007/0304-sea_urchins_reveal_medical_mysteries.htm)
Another fascinating fact is sea urchins don't have eyes, ears or a nose, but they have the genes humans have for vision, hearing and smelling.
24-04-2008, 10:43 PM
Newly Created Microbe Produces Cellulose And Sugars For Biofuels (http://www.sciencedaily.com/releases/2008/04/080423115917.htm)
Cyanobacteria were purposefully/intentionally modified to produce a relatively pure, gel-like form of cellulose that can be broken down easily into glucose and in turn can be used economically.
But, would a greater understanding of the biotic reality allow engineers to design a deeper purpose into the cyanobacteria? Could latent genes and genetic networks have been incorporated into the genome of the bacteria that are only activated by certain epigenetic factors in the future, thereby bypassing the the noise of stochastic processes and making use of natural selection?
E.g. Add a subset of genes to cyanobacteria that allows the cells to produce energy from various sources (E.g. H2S, various fatty acids, long chain alcohols, even radiation if possible) that are only specifically activated during UV-light deprivation, resulting either in cell senescence (thereby preventing cell death) or alternate pathways of energy production. In this way making use of natural selection to unfold future organisms capable of producing economical resources based on epigenetic factors alone and not random stochastic reactions.
Engineering foresight into an organism capable of making use of natural selection and epigenetic factors.
Engineering, understanding, agency, design...
05-05-2008, 06:11 PM
Those simple bacteria.
How Some Bacteria Survive Antibiotics (http://www.sciencedaily.com/releases/2008/04/080430154945.htm)
Describes the molecular mechanism of inducible antibiotic expression. Some bacteria have learned how to sense the presence of antibiotics in the ribosomal tunnel, and in response, switch on genes that make them resistant to the drug.
Epigenetic factors are increasingly coming to the forefront to describe a lot of evolutionary phenomena.
11-01-2010, 08:02 PM
Scientists Take a Step Towards Uncovering the Histone Code (http://www.sciencedaily.com/releases/2009/12/091220143925.htm)
ScienceDaily (Dec. 21, 2009) — Researchers at Emory University School of Medicine have determined the structures of two enzymes that customize histones, the spool-like proteins around which DNA coils inside the cell.
The structures provide insight into how DNA's packaging is just as important and intricate as the information in the DNA itself, and how these enzymes are part of a system of inspectors making sure the packaging is in order.
The results are published online this week in the journal Nature Structural and Molecular Biology.
A team of scientists led by Xiaodong Cheng, PhD, professor of biochemistry at Emory and a Georgia Research Alliance eminent scholar, used X-rays to probe the architecture of two enzymes, PHF8 and KIAA1718. The enzymes are known as histone demethylases because they remove methyl groups (chemical modifications of a protein) from histones.
Mutations in the gene encoding one of the enzymes, PHF8, cause a type of inherited mental retardation. Understanding how PHF8 works may help doctors better understand or even prevent mental retardation.
Many biologists believe the modifications on histones are a code, analogous to the genetic code. Depending on the histones' structure, access to DNA in the nucleus can be restricted or relatively free. The idea is: the modifications tell enzymes that act on DNA valuable information about getting to the DNA itself.
"This work represents a step toward uncovering the molecular basis for how demethylases handle multiple signals on histones," says Paula Flicker, PhD, who oversees cell signaling grants at the National Institutes of Health's National Institute of General Medical Sciences. "Knowledge of how these complex signals help govern patterns of gene activity will bring us closer to understanding how cells determine their identity during development."
To understand histone demethylases' role in the cell, Cheng says, think of the cell as a library with thousands of books in it.
"To find a particular book in a library, you need some signs telling you how the stacks are organized," he says. "Similarly, the machinery that reads DNA needs some guidance to get to the right place."
Histones have a core that the DNA wraps around and flexible tails extending beyond the core. The cells' enzymes attach a variety of bells and whistles -- methyl groups are just one -- to the histone tails to remind the cell how to handle the associated DNA.
Methyl groups mean different things depending on where they are on the histone. In addition, the modifications vary from cell to cell. In the brain, for example, the modifications on a particular gene might signal "this gene should be read frequently," and in muscle, a different set of modifications will say "keep quiet."
"What these enzymes do is make sure all the signs are consistent with each other," Cheng says. "If a sign is out of place, they remove it."
PHF8 and KIAA1718 are each made up of two attached modules. One module (called PHD) grabs a histone tail with a methyl group on it, while the other module (Jumonji) removes a methyl group from somewhere else on the tail.
Scientists previously knew the structures of the methyl-binding and methyl-removing modules in isolation. What is new is seeing how the modules are connected and how one part regulates the other, Cheng says.
The research was supported by the National Institutes of Health and the Georgia Research Alliance.
And another code: The epigenetic code.
For those interested in targeting the code for the treatment of....ageing, cancer, viral infections etc.
Defining an epigenetic code (http://www.nature.com/ncb/journal/v9/n1/full/ncb0107-2.html)
The “Epigenetic Code Replication Machinery”, ECREM: A Promising Drugable Target of the Epigenetic Cell Memory (http://www.ingentaconnect.com/content/ben/cmc/2007/00000014/00000025/art00001?crawler=true)
Unraveling the epigenetic code of cancer for therapy (http://www.cell.com/trends/genetics/abstract/S0168-9525%2807%2900243-0)
18-03-2010, 08:16 AM
Multiple codes with multiple programs:
How Cells Protect Themselves from Cancer (http://www.sciencedaily.com/releases/2010/03/100316101653.htm)
ScienceDaily (Mar. 18, 2010) — Cells have two different protection programs to safeguard them from getting out of control under stress and from dividing without stopping and developing cancer. Until now, researchers assumed that these protective systems were prompted separately from each other. Now for the first time, using an animal model for lymphoma, cancer researchers of the Max Delbrück Center (MDC) Berlin-Buch and the Charité -- University Hospital Berlin in Germany have shown that these two protection programs work together through an interaction with normal immune cells to prevent tumors.
Cascade which activates cell protection programs. (Credit: Graphic by Clemens Schmitt)
The findings of Dr. Maurice Reimann and his colleagues in the research group led by Professor Clemens Schmitt may be of fundamental importance in the fight against cancer. The research appears in the journal Cancer Cell.
Researchers have known for some time that -- paradoxically -- oncogenes themselves can activate these cell protection programs in an early developmental stage of the disease. This may explain why some tumors take decades to develop until the outbreak of the disease. The Myc oncogene triggers apoptosis (programmed cell death), inducing damaged cells to commit suicide in order to protect the organism as a whole. By means of chemotherapy, physicians activate this protection program to treat cancer.
The second protection program -- not as well understood as apoptosis -- is senescence (biological aging). This program is triggered by another oncogene, the ras gene. Senescence stops the cell cycle, and the cell can no longer divide. But in contrast to apoptosis the cell continues to live and is still metabolically active. Professor Schmitt, physician at Charité University Hospital and research group leader at the MDC, was able to show on an animal model for lymphoma that senescence can block the development of early-stage malignant tumors.
Myc oncogene triggers cascade to activate both protection programs
Now, for the first time, Dr. Reimann, Dr. Soyoung Lee, Dr. Christoph Loddenkemper, Dr. Jan R. Dörr, Dr. Vedrana Tabor and Professor Schmitt have provided evidence that the Myc oncogene plays a key role in the activation of both protection programs -- without the presence of the ras oncogene. "What is remarkable about this finding is that an oncogene can first trigger apoptosis and interact with the tumor stroma -- the tissue that surrounds the tumor which also contains healthy cells -- and with the immune system and then is able to switch on signals which lead to tumor senescence," Professor Schmitt said, summarizing how the interaction works.
According to the researchers' findings, the cascade occurs as follows: First the Myc oncogene triggers apoptosis in the lymphoma cells. The dying, apoptotic cells attract macrophages of the immune system, which devour and dispose of the dead lymphoma cells. The thus activated macrophages in turn secrete messenger molecules (cytokines), including the cytokine TGF-beta. It can block the growth of cancer cells in the early stage of a tumor disease. The MDC and Charité researchers discovered that the cytokines in the tumor cells that had escaped apoptosis switch on the senescence program and suppress the cancer cells.
"Our findings promise to have fundamental significance for elucidating the pathogenesis not only of lymphoma cancers, but of cancer in general. Our results indicate that senescence triggered by the immune system's messenger molecules may be a further important active principle, apart from apoptosis induced by chemotherapy."
At present the researchers in Professor Schmitt's group are focusing intensively on chemotherapy-mediated senescence. "If by inducing senescence we could obtain a sustained suppression of the cancer cells we can no longer destroy, this would mean exciting new possibilities for therapy," Professor Schmitt said.
Myc and RAS programs :whistle::p
20-08-2012, 06:21 PM
Another code cracked:
Molecular Code Cracked: Code Determines Recognition of RNA Molecules (http://www.sciencedaily.com/releases/2012/08/120820093759.htm)
ScienceDaily (Aug. 18, 2012) — Scientists have cracked a molecular code that may open the way to destroying or correcting defective gene products, such as those that cause genetic disorders in humans.
A molecular model of a PPR protein recognizing a specific RNA molecule. The identity of specific amino acid residues in the protein (colored sticks) determines the sequence of the RNA molecule it can bind. (Credit: Image courtesy of University of Western Australia)
The code determines the recognition of RNA molecules by a super-family of RNA-binding proteins called pentatricopeptide repeat (PPR) proteins.
When a gene is switched on, it is copied into RNA. This RNA is then used to make proteins that are required by the organism for all of its vital functions. If a gene is defective, its RNA copy and the proteins made from this will also be defective. This forms the basis of many terrible genetic disorders in humans.
RNA-binding PPR proteins could revolutionize the way we treat disease. Their secret is their versatility -- they can find and bind a specific RNA molecule, and have the capacity to correct it if it is defective, or destroy it if it is detrimental. They can also help ramp up production of proteins required for growth and development.
The new paper in PLoS Genetics describes for the first time how PPR proteins recognize their RNA targets via an easy-to-understand code. This mechanism mimics the simplicity and predictability of the pairing between DNA strands described by Watson and Crick 60 years ago, but at a protein/RNA interface.
This exceptional breakthrough comes from an international, interdisciplinary research team including UWA researchers Professor Ian Small and Aaron Yap from the ARC Centre for Excellence in Plant Energy Biology and Professor Charlie Bond and Yee Seng Chong from UWA's School of Chemistry and Biochemistry, along with Professor Alice Barkan's team at the University of Oregon. This research was publicly funded by the ARC and the WA State Government in Australia and the NSF in the USA.
"Many PPR proteins are vitally important, but we don't know what they do. Now we've cracked the code, we can find out," said ARC Plant Energy Biology Director Ian Small.
"What's more, we can now design our own synthetic proteins to target any RNA sequence we choose -- this should allow us to control the expression of genes in new ways that just weren't available before. The potential is really exciting."
"This discovery was made in plants but is applicable across many species as PPR proteins are found in humans and animals too," says Professor Bond.
21-08-2012, 09:49 PM
I've seen this episode of Star Trek. This leads to the Eugenics Wars, right? :p :D