New microarray chip improves drug safety, helps stop animal testing

Jonathan West a micro-engineer and his colleagues at the University of Dortmund in Germany, has  developed the new microarray chip which can test an estimated 30,000 chemicals  their toxicological risk.

Called a Network Formation Assay (NFA), the chip lets researchers test compounds faster and more reliably. A normal drug test takes up to 10 hours because each compound is tested 30 times at 10 different doses. With this new chip, it will take just a few hours at most.

This approach involves patterning neuronal cells within a hexagonal array to standardize the distance between neighbouring cellular nodes, and thereby standardize the length of the neurite interconnections. This feature coupled with defined assay coordinates provides a streamlined display for rapid and sensitive analysis

The invention includes a new protocol for the detection of the neurite outgrowth, which requires neither fixation nor staining of cells.

For details contact

http://www.provendis.info/?id=496&L=3

http://www.rsc.org/publishing/journals/LC/article.asp?Type=AdvArticle&Page=0&GA=on

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Surface plasmon resonance Imaging ushers in label free microarray analysis

Surface plasmon resonance (SPR) reflectivity measurements are surface-sensitive, spectroscopic methods that can be used to characterize the thickness and/or index of refraction of ultrathin organic and biopolymer films at gold, silver  surfaces.

The probes can be proteins, peptides, nucleic acids, sugars, membranes, or any other molecule. GWC Technologies is one such company that offers the services in this field

SPR imaging detects the presence of a biopolymer on a chemically modified gold surface by the change in the local index of refraction that occurs upon adsorption.

Research Papers are on , Uiversity of California, Irvine page   and also at

UC Davis Biophotonics center web page                  

CombiMatrix Molecular Diagnostics Launches Microarray Test for Detection of Autism Spectrum Disorder

CombiMatrix  has completed the clinical validation of the  BAC array CGH based clinical microarray tests. ATScan is designed to detect known genomic copy-number variations  associated with Autism Spectrum Disorder and this test is now available to physicians and consumers.

New Microarray technology replacing PCR and speed up HTS

Dr. Richard Gibbs, director of the Baylor College of Medicine Human Genome Sequencing Centre and his researchers along with the help of  NimbleGen Systems the  company recently acquired by Roche Applied Science has developed a new technique that combines gene chip technology with the latest generation of gene sequencing machines to allow fast and accurate sequencing of selected parts of the genome

 The technology, called “sequence capture,” enables fast and accurate enrichment of thousands of selected genomic regions, either contiguous or dispersed, such as segments of chromosomes or all genes or exons uses , The study had uses NimbleChip™ microarrays in preparation for a high-throughput 454 Sequencing™.

The study Direct Selection of Human Genomic Loci by Microarray Hybridization presented on October 10, 2007, at the J. Craig Venter Institute’s Genomes, Medicine, and the Environment (GME) conference, Roche NimbleGen and 454 Life Sciences, working with Dr. Richard , will create a whole-genome human exome (all exons) microarray, with the goal of resequencing the entire human exome faster and cheaper.

Till now researchers relied upon PCR for selection of specific genomic regions for resequencing

Limitations of PCR  meant the length of sequence it can amplify was small, is difficult to scale or multiplex for the enrichment of thousands of fragments, and has limited performance in the repetitive regions typical of complex genomes, such as human.

The sequence capture microarray technology bridges the gap between next-generation DNA sequencing technology and current sample preparation methods by providing an adaptable, massively parallel method for selective enrichment of genomic regions of interest.

The new process is simpler, more accurate and efficient than the multiplex PCR . In one experiment, more than 6,400 exons (the part of the genetic code that carries the instructions for making proteins), were analyzed. Using the old technology this would have taken at least six months.

Transposon insertion site profiling chip (TIP-chip)

Transposon insertion site profiling chip (TIP-chip) was invented by Researchers at the Johns Hopkins’ High Throughput Biology Center. Tip-chip can be used to help identify otherwise elusive disease-causing mutations in the 97 percent of the genome long believed to be “junk.”

TIP-chip (transposable element insertion point) can locate in the genome where so-called jumping genes have landed and disrupted normal gene function. This chip is described n the Proceedings of the National Academy of Sciences. the article titled Eukaryotic Transposable Elements and Genome Evolution Special Feature: Transposon insertion site profiling chip (TIP-chip

The most commonly used gene chips are glass slides that have arrayed on them neat grids of tiny dots containing small sequences of only hand-selected non-junk DNA. TIP-chips contains all DNA sequences. Because each chip can hold thousands of these dots – even a whole genome’s worth of information – scientists in the future may be able to rapidly and efficiently identify, by comparing a DNA sample from a patient with the DNA on the chip, exactly where mutations lie.

Jef Boeke, Ph.D., Sc.D, professor of molecular biology and genetics and director of the HiT (High Throughput Biology Center), who spearheaded both studies at the Institute of Basic Biomedical Sciences at Hopkins, and his team have focused particularly on transposable elements, segments of DNA that hop around from chromosome to chromosome.

These elements can, depending on where they land, wrongly turn on or off nearby genes, interrupt a gene by lodging in the middle of it, or cause chromosomes to break. Transposable elements long have been suspected of playing a role vital to disease-causing mutations in people. Boeke hopes that the TIP-chip eventually can be used to look for such mutations in people.

The new TIP-chip contains evenly sized fragments of the yeast genome arrayed in dots left to right in the same order as they appear on the chromosome. Boeke’s team used the one-celled yeast genome as starting material because, unlike the human genome, which contains hundreds of thousands of transposable elements of which perhaps a few hundred are actively moving around, the yeast genome contains only a few dozen copies.

Like a word-find puzzle, where words are hidden in a jumbled grid of letters, the TIP-chip highlights exactly where along the DNA sequence these elements have landed. By chopping up the DNA, amplifying the DNA next to the transposable elements and then applying these amplified copies to the TIP chip, the researchers were able to map more than 94 percent of the transposable elements to their exact chromosome locations.

double-tiled DNA chip 

Standard chips contain one layer of DNA dots that read from left to right, like the across section of a crossword puzzle. Boeke’s new double-capacity chips hold two layers of dots, a bottom layer that reads across and a top layer that reads down, again using the crossword analogy. So if their experiment lights up a horizontal row of dots, the researchers learn that the data maps to the region of the genome contained in the bottom layer; likewise, if the experiment highlights a vertical row, the data correspond to the top layer.

Says Boeke, “It’s so easy to differentiate the top and bottom layers. Next we’re going to try adding another layer reading diagonally” to triple the amount of genomic information packed onto the tiny chips.

Authors of the TIP-chip and double-tiled DNA chip papers are Sarah Wheelan, a new faculty member in the Department of Oncology, Lisa Scheifele, Francisco Martinez-Murillo, Rafael Irizarry and Boeke, all of Hopkins.

IS Microarray facing the DOOM….Invading microarray turf……….

ChIP-sequencing (ChIPSeq) – a combination of chromatin immunoprecipitation and next-generation, or parallel, sequencing. The feat was performed “with a speed and precision that goes beyond what has been achieved with previous technologies,” comments University of Washington geneticist Stanley Fields, in an accompanying essay in Science.

hIP is a well-established lab technique to identify those specific sites where proteins latch onto the DNA. Cells are treated with a chemical to fossilize the links between DNA and protein, the chromatin is then isolated, the DNA broken up, and the attached proteins immunoprecipitated. Finally, the DNA stuck to the protein can be released and analyzed. Until now, the most high-throughput application of this technique involved using microarrays containing thousands of gene spots able to identify binding sites for transcription factors and the like.

Next-Generation Sequencing Invades Microarray Turf By Kevin Davies June 14, 2007 | Two new papers unveil a new dimension to commercial next-generation sequencing applications – one that could potentiallypose a threat to more-established microarray technologies. Using theGenome Analyzer from Illumina/Solexa, two groups working independentlyhave been able to map the locations across the genome where a specific
DNA-binding protein latches onto the DNA.

ChIPSeq is a cost-effective alternative to microarray methods, with a significant upside. “Other ultrahigh-throughput sequencing platforms, such as the one from 454 LifeSciences, could also be used to assay ChIP products, but whatever sequencing platform is used, our results indicate that read numbercapacity and input ChIP DNA size are key parameters,” Johnson et al. writes.ChIPSeq might be an order of magnitude cheaper than microarray alternatives, with the eight flow cell lanes in theGenome Analyzer offering excellent design flexibility. Fewer materialsare required, and the method can be applied to any organism – it is not restricted to available gene arrays.

Changing ChIPs
The advantages of ChIPSeq over ChIP-chip include the ability to interrogate the entire genome rather than just the genesrepresented on a microarray. (For example, Johnson et al. point out thata similar experiment using Affymetrix-style microarrays would requireroughly 1 billion features per array.) There is also the benefit of
sidestepping known hybridization complications with microarrayplatforms. “Perhaps most usefully,” writes Fields, “ChIPSeq canimmediately be applied to any of those [available] genomes, rather thanonly those for which microarrays are available.”

its not so much of junk DNA- University of Oxford Scientists discoveres Cancer cure with it

 Junk DNA is not junk after all

Recently, scientists at the University of Oxford have discovered that ‘junk’ genetic material can switch off cancer tumours, preventing them from growing.

By using RNA to switch off a gene involved in controlling cell division, Oxford University scientists may have found a role for RNA in developing new cancer therapies. RNA is the mirror image of DNA, and is used to pass on instructions to the cell to build the proteins that run every body function.

The Human Genome Project found that human DNA carries approximately 34,000 genes that produce proteins. The remaining majority of the genome constituted what was considered to be junk DNA as it had no obvious function. However, this is set to change.

‘‘There has been a quiet revolution taking place in biology in past few years,’’ said Dr Alexandre Akoulitchev, a Senior Research Fellow at Oxford. ‘‘Scientists have begun to see ‘junk’ DNA as having an important function. The variety of RNA types produced from this so called ‘junk’ is staggering and the functional implications are huge.”

Akoulitchev studied the RNA that regulates a gene called DHFR. This gene produces an enzyme that controls the production of molecules called tetrahydrofolate and thymine that cells need to divide rapidly.

“Switching off the DHFR gene could help prevent ordinary cells from developing into cancerous tumour cells, by slowing down their replication. In fact, one of the first anti-cancer drugs, Methotrexate, acts by binding and inhibiting the enzyme produced by this gene. Targeting the gene itself would cut the enzyme out of the picture altogether. Understanding how we can use RNA to switch off or inhibit DHFR and other genes may have important therapeutic implications for developing new anti-cancer treatments.”

This research was funded by The Wellcome Trust and the Medical Research Council.

Original paper: Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript was published in Nature on 22nd January 2006.

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