Bioengineers Devise ‘Dimmer Swith’ To Regulate Gene Expression In Mammal Cells

Three Boston University biomedical engineers have created a genetic dimmer switch that can be used to turn on, shut off, or partially activate a gene’s function. Professor James Collins, Professor Charles Cantor and doctoral candidate Tara Deans invented the switch, which can be tuned to produce large or small quantities of protein, or none at all

This switch helps advance the field of synthetic biology, which rests on the premise that complex biological systems can be built by arranging components or standard parts, as an electrician would to build an electric light switch. Much work in the field to date uses bacteria or yeast, but the Boston University team used more complex mammalian cells, from hamsters and mice. The switch has several new design features that extend possible applications into areas from basic research to gene therapy.

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Scientists find key to stem cell immortality

One of the medical marvels of stem cells is that they continue to divide and renew themselves when other cells would quit. But what is it that gives stem cells this kind of immortality. Researchers now report in the June 16, 2005 issue of the journal Nature that microRNAs — tiny snippets of genetic material that have now been linked to growth regulation in normal cells as well as cancer growth in abnormal cells — appear to shut off the “stop signals” or brakes that would normally tell cells to stop dividing.

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Virus Uses Tiny RNA To Evade The Immune System

In the latest version of the hide-and-seek game between pathogens and the hosts they infect, researchers have found that a virus appears to cloak itself with a recently discovered gene silencing device to evade detection and destruction by immune cells.

The report by Howard Hughes Medical Institute (HHMI) researchers in an article published in the June 2, 2005, issue of Nature may be the first to show how a virus uses the gene silencing machinery for its own infectious purposes.

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Mechanism of microRNAs deciphered

Over 30% of our genes are under the control of small molecules called microRNAs. They prevent specific genes from being turned into protein and regulate many crucial processes like cell division and development, but how they do so has remained unclear. Now researchers from the European Molecular Biology Laboratory (EMBL) have developed a new method that uncovered the mode of action of microRNAs in a test tube. The study, which is published in the current online issue of Nature, reveals that microRNAs block the initiation of translation, the earliest step in the process that turns genetic information stored on messenger RNAs into proteins.
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Carbon Nanotubes versus HIV

Researchers at Stanford University have added one more trick to carbon nanotubes’ repertoire of accomplishments: a way to fight the human immunodeficiency virus (HIV). Chemistry professor Hongjie Dai and his colleagues have used carbon nanotubes to transport RNA into human white blood cells that defend the body from disease, making the cells less susceptible to HIV attack.

In a paper now online in the journal Angewandte Chemie, Dai and his colleagues describe attaching RNA to carbon nanotubes, which enter T cells and deliver the RNA. When the researchers placed T cells in a solution of the carbon nanotube-RNA complex, receptor proteins on the cell surfaces went down by 80 percent. Carbon nanotubes are known to enter many different types of human cells, although researchers don’t understand exactly how they do it. Some experts suspect that because of their long, thin shape, nanotubes enter cells much as a needle passes through skin.

Read rest of the story on Technology Review site

Regulating the nuclear architecture of the cell

An organelle called the nucleolus resides deep within the cell nucleus and performs one of the cell’s most critical functions: it manufactures ribosomes, the molecular machines that convert the genetic information carried by messenger RNA into proteins that do the work of life.

Gary Karpen and Jamy Peng, researchers in the Life Sciences Division of the Department of Energy’s Lawrence Berkeley National Laboratory, have now discovered two pathways that regulate the organization of the nucleolus and other features of nuclear architecture, maintaining genome stability in the fruit fly Drosophila melanogaster.
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Reprogramming Biology

Visionary futurist Ray Kurzweil, whose remarkable ideas on technological progress have been an inspiration for Biosingularity blogs, have a wonderful concise article on biological advances in recent issue of Scientific American

As a scientist working on biological systems I fully agree and whole heartedly support Kurzweil's observations that: " Biology is now in the early stages of an historic transition to an information science, while also gaining the tools to reprogram the ancient information systems of life ….. We are now beginning to understand biology as a set of information processes, and we're developing realistic models and simulations of how the processes involved in disease and aging progress. Moreover, we are developing the tools to reprogram them."

In the article Kurzweil predicts that tinkering with our genetic programs will extend human lifespan beyond the current limits. He also reiterates that biological systems are also subject to the "law of accelerating returns", which had tremendous impact on information technologies. Indeed, the cost of sequencing and synthesizing gene base pairs have decreased more than 10,000 fold over the last 15 years, and this exponential progress is currently accelerating as predicted by Kurzweil in his recent book. 

Read rest of the article at Scientific American web site.
 

Single microRNA causes cancer in transgenic mouse

Scientists in the Ohio State University Comprehensive Cancer Center say that just one, single, malfunctioning microRNA is sufficient to cause cancer in mice. The discovery offers new insight into the development of some forms of leukemia and lymphoma and at the same time underscores the powerful role that these tiny snippets of non-coding RNA play in cell signaling pathways active in carcinogenesis.

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Tiny RNA molecules fine-tune the brain’s synapses

Non-coding regions of the genome – those that don’t code for proteins – are now known to include important elements that regulate gene activity. Among those elements are microRNAs, tiny, recently discovered RNA molecules that suppress gene expression. Increasing evidence indicates a role for microRNAs in the developing nervous system, and researchers from Children’s Hospital Boston now demonstrate that one microRNA affects the development of synapses – the points of communication between brain cells that underlie learning and memory.

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A method is developed to silence genes in specific tissues using RNAi

Researchers at The University of Texas M. D. Anderson Cancer Center say they have jumped a significant hurdle in the use of RNA interference (RNAi), believed by many to be the ultimate tool to both decode the function of individual genes in the human genome and to treat disease.

Reporting in the journal Genes and Development, investigators have developed a simple way to use the RNAi approach to silence a selected gene in a specific tissue in a mouse to determine the function of that targeted gene.

This is another major breakthrough related to RNA interferene that was the topic of my prior post.
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What is RNA interference?

This is first in series of mini-commentaries that I hope will provide background and context to the importance some of the major discoveries that I have posted.

This week’s feature is RNA interference (RNAi). There is a great mini-tutorial about RNAi at PBS Nova site. The the wiki on RNAi is also useful for providing simple background.

RNAi is arguably the most important molecular biology discovery of the last decade and was declared breakthrough of the year by Science magazine in 2002. This technology has the potential to transform medicine but providing us the tool to regulate expression of genes. RNAi mediated treatments may also become the next big thing in biotech.

I recently reported about the structure of the key RNAi component, Dicer protein. This story revealed new insight into the intricate mechanism of RNAi. Several other discoveries posted here also involved RNAi.

The structure of a protein called Dicer reveals new insight into gene silencing

A team of scientists has peeled back some of the mystery of how cells are able to turn off genes selectively to control critical events of development. The new insights arise from the first clear molecular images of the structure of Dicer, an enzyme that enables cells to dissect genetic material precisely.

The findings provides scientists with new information about a mechanism that enables cells to silence genes, a process that governs key developmental events ranging from brain development to stem cell differentiation.

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Long-term memory controlled by molecular pathway at synapses

Harvard University biologists have identified a molecular pathway active in neurons that interacts with RNA to regulate the formation of long-term memory in fruit flies. The same pathway is also found at mammalian synapses, and could eventually present a target for new therapeutics to treat human memory loss.

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Sickle cell disease corrected in human models using stem cell-based gene therapy

In a study to be published in the January 2006 issue of Nature Biotechnology, researchers led by a team of scientists at Memorial Sloan-Kettering Cancer Center have devised a novel strategy that uses stem cell-based gene therapy and RNA interference to genetically reverse sickle cell disease (SCD) in human cells. This research is the first to demonstrate a way to genetically correct this debilitating blood disease using RNA interference technology.
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Scientists Discover a Gene That Regulates Lifespan

Genes that control the timing of organ formation during development also control timing of aging and death, and provide evidence of a biological timing mechanism for aging, Yale researchers report in the journal Science.

“Although there is a large variation in lifespan from species to species, there are genetic aspects to the processes of development and aging,” said Frank Slack, associate professor of Molecular, Cellular and Developmental Biology and senior author of the paper. “We used the simple, but genetically well-studied, C. elegans worm and found genes that are directly involved in determination of lifespan. Humans have genes that are nearly identical.”

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Researchers hone in on differentiation of heart stem cells

A team of scientists from the Gladstone Institute of Cardiovascular Disease (GICD) has identified a key factor in heart development that could help advance gene therapy for treating cardiac disorders.

The findings could help cardiac stem cell researchers one day develop strategies for gene and cell- mediated cardiac therapies.

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New Study Expands Understanding Of The Role Of RNA Editing In Gene Control

For many years, scientists thought gene activity was relatively straightforward: Genes were transcribed into messenger RNA, which was processed and translated into the proteins of the body. Certainly, there were many factors governing the transcription process, but gene control happened at the level of the DNA

In the past few years, however, evidence for a more nuanced understanding of the total genetic system has steadily accumulated. Researchers at The Wistar Institute and elsewhere have been teasing out the details of a process called RNA editing, in which messenger RNA sequence is altered after transcription by editing enzymes, so that a single gene can produce a number of related but distinct variant proteins. Most recently, scientists have discovered an extensive family of small molecules called microRNAs, or miRNAs, that appear to target and inactivate particular messenger RNAs. This targeted gene silencing is now seen as one of the body’s primary strategies for regulating its genome.
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Regeneration Gene Possibly Found

Researchers at the University of Utah have discovered that when a gene called smedwi-2 is silenced in the adult stem cells of planarians, the quarter-inch long worm is unable to carry out a biological process that has mystified scientists for centuries: regeneration.

Elimination of smedwi-2 not only leads to an inability to mount a regenerative response after amputation, but also to the eventual demise of unamputated animals along a reproducible series of events, that is, regression of the head tip, curling of the body and tissue disintegration. These defects are very similar to what is observed after the planarian stem cells are destroyed by lethal doses of irradiation. The key difference, however, is that the irradiation-like defects observed in animals devoid of smedwi-2 occur even though the stem cells are still present in the organism.
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