Tuesday, 15 July 2008

Weekly BioNews 7 - 14 Jul 2008

- DNA sewing machine

July 10, 2008 07:33 PM

Japanese scientists have made a micro-sized sewing machine to sew long threads of DNA into shape. The work published in the Royal Society of Chemistry journal Lab on a Chip demonstrates a unique way to manipulate delicate DNA chains without breaking them.

Scientists can diagnose genetic disorders such as Down's syndrome by using gene markers, or "probes", which bind to only highly similar chains of DNA. Once bound, the probe's location can be easily detected by fluorescence, and this gives information about the gene problem.

Detecting these probes is often a slow and difficult process, however, as the chains become tightly coiled. The new method presented by Kyohei Terao from Kyoto University, and colleagues from The University of Tokyo, uses micron-sized hooks controlled by lasers to catch and straighten a DNA strand with excellent precision and care.

"When a DNA molecule is manipulated and straightened by microhooks and bobbins, the gene location can be determined easily with high-spatial resolution," says Terao.

The team used optical tweezers – tightly focused laser beams – to control the Z-shaped micro hook and pick up a single DNA "thread". The hook is barbed like an arrow, so the thread can't escape. When caught on the hook, the DNA can be accurately moved around by refocusing the lasers to new positions.

But just like thread in a sewing machine, a long DNA chain can be unwieldy – so the researchers built micro "bobbins" to wind the chain around. The lasers move one bobbin around another, winding the DNA thread onto a manageable spindle...

- Scientists Identify Genetic Basis For The Black Sheep Of The Family

ScienceDaily (July 11, 2008)

Coat color of wild and domestic animals is a critical trait that has significant biological and economic impact. Researchers have now identified the genetic basis for black coat color, and white, in a breed of domestic sheep.

In the wild, mammalian coat color is essential for camouflage and plays a role in social behavior. Coat color also strongly influences the animals we choose to breed both as livestock and as pets. Understanding the genetic determinants of coat color in livestock species such as sheep, specifically bred for their coat color, is critical for improving efficient selection of the desired trait.

Classical genetics has associated alternative forms, or alleles, of the agouti signaling protein gene (ASIP) with coat color variation in a number of mammals including mice, rats, dogs, cats, pigs, and sheep. However, most research has been focused on the mouse, with little understood about the genetic basis for coat color in economically important livestock species such as sheep.

The wild-type coat color of sheep is typically dark-bodied with a pale belly, however sheep raisers have strongly selected for a uniformly white coat domestic sheep. A problem for the sheep industry is a recessive black "non-agouti" allele of the ASIP gene carried by white sheep that cannot be distinguished within the flock, resulting in black coat color at a low, but persistent frequency. Determining the exact genetic differences at the ASIP locus could assist in efficient selection for white coat color.

Scientists at the CSIRO Queensland Bioscience Precinct in Australia have now taken this step and identified the molecular mechanisms underlying white and black coat color in domestic sheep. The researchers investigated the genetic architecture of the ASIP gene in several sheep breeds by sequencing the ASIP locus and measuring gene expression. "Surprisingly what we found was in fact that the genetic cause of domestic white and black sheep involves a novel tandem duplication affecting the ovine agouti gene and two other neighboring genes, AHCY and ITCH," explains Dr. Belinda Norris, lead author of the study....

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- New Mode Of Gene Regulation Discovered In Mammals

ScienceDaily (July 13, 2008)

Researchers at the University of California, Santa Cruz, have discovered a type of gene regulation never before observed in mammals -- a "ribozyme" that controls the activity of an important family of genes in several different species.

The findings, published July 9 in the journal Nature, describe a new and surprising role for the so-called hammerhead ribozyme, an unusual molecule previously associated with obscure virus-like plant pathogens called viroids. The UCSC researchers found the ribozyme embedded within certain genes in mice, rats, horses, platypuses, and several other mammals. The genes are involved in the immune response and bone metabolism.

"The unique thing about these ribozymes is that they control the expression of the genes they're embedded in," said Monika Martick, a UCSC postdoctoral researcher and first author of the Nature paper.

A ribozyme, or "RNA enzyme," is an RNA molecule that can catalyze a chemical reaction. RNA is better known for its ability to encode genetic information, while most biological reactions are carried out by enzymes made of protein. Scientists are discovering, however, that RNA is a remarkably versatile type of molecule.

"RNA can function in the biology of organisms in more ways than we tend to give it credit for," said coauthor Lucas Horan, a graduate student in molecular, cell, and developmental biology at UCSC.

When a gene is activated or "expressed," its DNA sequence on the chromosome is transcribed into an RNA molecule called a messenger RNA. The messenger RNA sequence is then translated into the amino acid sequence of a protein molecule, and the protein then carries out the gene's function in the cell.

In the genes studied by Martick and Horan, the messenger RNA contains sequences that assemble to form an active hammerhead ribozyme. The hammerhead ribozyme is a self-cleaving molecule that essentially cuts itself in two. This self-cleaving action in the messenger RNAs effectively turns off the genes by preventing protein translation. Presumably, another mechanism exists to turn on the genes by stopping the self-cleaving action of the ribozyme...

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- Toothpick: New Molecular Tag IDs Bone And Tooth Minerals

ScienceDaily (July 15, 2008)

Enlisting an army of plant viruses to their cause, materials researchers at the National Institute of Standards and Technology (NIST) have identified a small biomolecule that binds specifically to one of the key crystal structures of the body--the calcium compound that is the basic building block of teeth and bone. With refinements, the researchers say, the new molecule can be a highly discriminating probe for a wide range of diagnostic and therapeutic applications related to bones and teeth.

Although they have somewhat different mechanical properties, the major structural component of both teeth and bones is a crystalline compound of calcium phosphate called hydroxyapatite. Subtle variations in the way the crystal forms account for the differences. Identifying and monitoring the formation of this particular crystal is of paramount importance to biomedical researchers working on a variety of problems including the remineralization of teeth to repair decay damage, the integration of prosthetic joints and tissue-engineered bone materials for joint and bone replacement, and cell-based therapies to regrow bone tissue.

To date, however, there is no specific, practical method to spot the formation of hydroxyapatite in living systems or tissue samples. Materials scientists can identify the crystal structure with high reliability by the pattern it makes scattering X rays, but it's a complex procedure, requires fairly pure samples and certainly can't be used on living systems. There are some widely used chemical assays--the von Kossa assay, for example--but these also are destructive tests, and more importantly they really test simply for the presence of the elements calcium or phosphorus. They can't distinguish, for example, between deposits of amorphous calcium phosphate--a precursor--and the hydroxyapatite crystal....

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- Ebola protein discovery

Date: 10/07/2008

Described in the July 10, 2008 issue of the journal Nature, the research reveals the shape of the Ebola virus spike protein, which is necessary for viral entry into human cells, bound to an immune system antibody acting to neutralise the virus. The structure provides a major step forward in understanding how the deadly virus works, and may be useful in the development of potential Ebola virus vaccines, or treatments for those infected."Much about Ebola virus is still a mystery," says Erica Ollmann Saphire, the Scripps Research scientist who led the five-year effort. "However, this structure now reveals how this critical piece of the virus is assembled and, importantly, identifies vulnerable sites that we can exploit."

There is currently no cure for Ebola hemorrhagic fever. The virus is spread when people come into contact with the bodily fluids of someone who is already infected. Most ultimately die from a combination of dehydration, massive bleeding, and shock. The best treatment consists of administering fluids and taking protective measures to ensure containment, like isolating the patient and washing sheets with bleach.

The breakthrough described in the Nature article, though, provides hope that one day modern medicine will have more to offer.

The structure of the antibody together with the viral glycoprotein helps reveal the mechanisms by which the molecules assemble on the viral surface and helps explain how the pathogen evades and exploits the human immune system. The structure also provides a guide for the design of drugs and vaccines to block this protein, potentially preventing disease and death.

The new research was made possible by an antibody isolated by Dennis Burton, a Scripps Research professor and one of the study's coauthors. The antibody-shown bound to the Ebola virus spike protein in the current research-was derived from bone marrow of one of the few survivors of the 1995 Ebola outbreak in Kikwit, a city in the southwestern part of the Democratic Republic of Congo. The Kikwit outbreak was particularly deadly, with a higher than 90 percent mortality rate for those infected.

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