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Researchers Discover Technology that Silences Genes

Tue, 19 Aug 2008 12:30:59 +0200

New York, NY (OBBeC) - A team of researchers led by Ming-Ming Zhou at Mount Sinai School of Medicine have developed a new gene silencing technology that they believe could be used to target genes that can lead to the development of certain diseases.

The findings, which will be published in the September issue of Nature Cell Biology, are available on the magazine's web site.

"By being able to silence certain genes, we may be able to suppress genes that can cause diseases such as HIV/AIDS, cancer, inflammation and diseases of the central and peripheral nervous systems. We now know we can focus on these genes and potentially change the ultimate course of many diseases that have a major impact on people's lives," says Dr. Zhou, Professor and Chairman of the Department of Structural and Chemical Biology at Mount Sinai School of Medicine.

In the study, Dr. Zhou, Dr Shiraz Mujtaba, Assistant Professor of Structural and Chemical Biology at Mount Sinai and their colleagues discovered that Paramecium bursaria chlorella virus uses a viral protein to modify host DNA packing chromatin and switch host transcription machinery for viral replication. Based on this finding, researchers were able to develop a new gene targeting technology that effectively suppresses transcriptional expression of targeted genes in human cells, including genes that are linked to the onset of a number of diseases.

New ADVIA CentraLink Informatics Product Released

Tue, 19 Aug 2008 12:12:46 +0200

Deerfield, Ill (OBBeC) - Siemens Healthcare has announced the launch of a new version of the ADVIA CentraLink informatics product that allows clinical laboratory customers to improve workflow, operational efficiency and management of patient data.

According to the company, this new (version 12) software will help to reduce overall costs in the laboratory and also improve the laboratory’s support of patient care in their facility. It connects multiple diagnostic instruments to a laboratory information system (LIS) in a stand-alone or automation configuration.  

“Informatics is one of the fastest moving fields in the clinical laboratory industry. It’s a powerful tool for impacting laboratory workflow and helping the laboratory increase quality while still reducing costs,” said Eric Olson, vice president, informatics and eBusiness, Siemens Healthcare Diagnostics. “The new ADVIA CentraLink software is an important step in advancing customers’ ability to automate processes that cost the most time and money. It provides seamless information technology (IT) integration and increases customers’ productivity and capacity to the highest level yet.”

Some of the new software features include:
Ability to connect up to 32 diagnostic instruments, including molecular, and also two ADVIA automation systems—all serviced and supported by one manufacturer—allowing customers to automate more processes than before, save time and reduce costs;

Remote connectivity to a single ADVIA CentraLink server enabling hospital networks with multiple laboratory locations to consolidate patient data into one system, and drive consistency through the network;

Increased database capacity benefiting high-volume laboratories.

New patient data management upgrades benefiting all sizes of laboratories: more delta checking functions, new quality control and autoverification capabilities, enhanced error logging, sample query improvements and enhanced communications with laboratory information systems (LIS).

ADVIA CentraLink supports all ADVIA chemistry, immunochemistry and hematology instruments, and also a molecular, urinalysis and third-party coagulation instrument. Siemens is currently investing in new ADVIA CentraLink versions that are compatible with instruments in the company’s recently expanded product portfolio.

Helicos BioSciences Receives Technology Innovation Award

Tue, 19 Aug 2008 11:53:51 +0200

Palo Alto, CA (OBBeC) - Frost & Sullivan, based on its recent analysis of the genome/transcriptome sequencing market, has presented Helicos BioSciences with the 2008 North American Frost & Sullivan Award for Technology Innovation of the Year.

According to the announcement from Frost & Sullivan, this Award is in recognition of Helicos' introduction of an advanced single-molecule sequencing platform that allows an entire genome to be cost-effectively sequenced in a very short amount of time.

Standard methods for sequencing genes require that the DNA be amplified many times – a time-consuming and expensive process. The first human genome was completed in 2003 after 3 years and a cost of 2.5 Billion Dollars. Last year, the first individual human genome was sequenced just a year ago for a cost of about $1 million.

Further to the announcement, the Helicos Genetic Analysis System enables extremely high-throughput genetic analysis by directly sequencing individual molecules of DNA. This allows an entire genome to be sequenced in about two weeks, for a cost of about $36,000.

"Single-molecule DNA sequencing has been a goal of the scientific community for over 40 years," says Frost & Sullivan Research Analyst Dr. Kathryn Austin. "Helicos' proprietary True Single Molecule Sequencing (tSMS) technology, enables the simultaneous sequencing of large numbers of strands of single DNA or RNA molecules."

The tSMS technology – developed from the work of Dr. Stephen Quake at Stanford University – uses a proprietary form of "sequencing-by-synthesis", in which labelled DNA bases are sequentially added to the nucleic acid templates captured on a "flow cell". Each base addition is detected by the HeliScope Single Molecule Sequencer, which is at the heart of the system. This way the entire sequence of bound strands can be elucidated.

The tSMS technology enables the direct analysis of individual DNA molecules, without requiring a large number of copies of those molecules. The system does not require elaborate sample processing or amplification techniques, dramatically lowering the cost of individual genomic and genetic analyses. The simple sample preparation process can easily be scaled and replicated to meet the requirements of large, complex experiments, overcoming the workflow bottlenecks encountered by methods such as PCR or cloning.

"As an enabling technology for genomics research, Helicos' technology platform will allow researchers to accelerate their understanding of important but extremely complex diseases such as cancer and heart disease," notes Austin. "The Helicos Genetic Analysis System will have extensive applications in basic and pharmaceutical R&D, from diagnostics to prognostic indicators to more effective therapies, increasing the potential for personalized medicine and more accurate molecular diagnostics. One especially promising capability is rapid sequencing of the "transcriptome", allowing quantitative analysis of gene expression through mRNA levels."

The company is planning future generations of chemistry that will ultimately allow customers to access the full power of the HeliScope Sequencer and enable human genome analysis at or below $1,000.

For these achievements, Frost & Sullivan has present Helicos BioSciences with the 2008 Award for Technology Innovation of the Year.

Each year, Frost & Sullivan presents this Award to the company that has carried out new research, which has resulted in innovation(s) that have or are expected to bring significant contributions to the industry in terms of adoption, change, and competitive posture. The Award recognizes the quality and depth of a company's research and development program as well as the vision and risk-taking that enabled it to undertake such an endeavour.

Ingenuity Systems Introduces Analysis Services

Mon, 18 Aug 2008 13:16:09 +0200

Redwood City, CA (OBBeC) - Ingenuity Systems, a provider of information solutions for life science researchers, has announced the launch of Ingenuity Analysis Services, custom-tailored professional scientific services for scientists working with 'omics data related to compound profiling, target identification, and mechanism of action studies.

According to the company, the new services are designed to meet the needs of research teams that require a rapid turnaround for a project, or who do not have the required resources internally.

"Ingenuity Analysis Services provides relevant and actionable analysis results quickly," said Sean Scott, SVP Commercial Operations, Ingenuity Systems. "We are seeing an analysis outsourcing trend in the pharmaceutical and biotech industry because maintaining a fully trained and current analysis skill set in-house is not always the most efficient and effective way to get fast and high quality analysis results. Many of these organizations have reached out to us for analysis services because of their long partnership with IPA and their trust in the quality of knowledge and analysis results that Ingenuity delivers."

Microbial Analysis Shows the Power of Metagenomic Approaches

Mon, 18 Aug 2008 12:30:59 +0200

Walnut Creek, CA (OBBeC) - In a paper which appeared in Nature Biotechnology August 17, a collaboration headed by researchers at the University of Washington and the U.S. Department of Energy Joint Genome Institute (DOE JGI) describes a novel approach for extracting single genomes and discerning specific microbial capabilities from mixed community ("metagenomic") sequence data.

Using an enrichment technique applied to microbial community samples, the research team explored the sediments in Lake Washington, bordering Seattle, WA and characterized biochemical pathways associated with nitrogen cycling and methane utilization, important for understanding methane generation and consumption by microbes. Methane is both a greenhouse gas and a potential energy source.

"Even if you have lots of sequence, for complex communities it still doesn't tell you which organism is responsible for which function," said the paper's senior author Ludmila Chistoserdova, a microbiologist at the University of Washington. "This publication presents an approach, via simplification and targeted metagenomic sequencing, of how you can go after the function in the environment."

Chistoserdova and colleagues study microbes that oxidize single-carbon compounds such as methane, methanol and methylated amines, which are compounds contributing to the greenhouse effect and are part of the global carbon cycle.

"To utilize these single-carbon compounds, organisms employ very specialized metabolism," said Chistoserdova. "We suspect that in the environment, there are novel versions of this metabolism, and possibly completely novel pathways."

Most of the microbes that oxidize single-carbon compounds are unculturable and therefore unknown, as are the vast majority of microbes on Earth. To find species of interest, the researchers sequenced microbial communities from Lake Washington sediment samples, Chistoserdova said, because lake sediment is known to be a site of high methane consumption. However, these sediment samples contained over 5,000 species of microbes performing a complex, interconnected array of biochemical tasks.

To enrich the samples for the microbes of interest, the researchers adapted a technique called stable isotope probing. This is the first time the technique has been used on a microbial community, Chistoserdova said. The researchers used five different single-carbon compounds labelled with a heavy isotope of carbon, and fed each compound to a separate sediment sample. The microbes that could consume the compound incorporated the labeled carbon into their DNA, Chistoserdova said, while organisms that couldn't use the compound did not incorporate the label. The labelled DNA was then separated out and sequenced. In this way, microbial "subsamples" were produced that were highly enriched for organisms that could metabolize methane, methanol, methylated amines, formaldehyde and formate.

The functionally enriched samples contained far fewer microbes than the total sample, Chistoserdova said. The sample that was fed methylated amines was simple enough that the group was able to extract the entire genome of a novel microbe, Methylotenera mobilis, that normally comprises less than half a percent of the community, but appears to be a first responder to methylated amines in the environment. The researchers were able to construct much of M. mobilis' biochemistry, and predict that it is also involved in nitrogen cycling, demonstrating the utility of metagenomic analysis.

The DOE JGI performed the sequencing and assembly of these complex metagenomic data sets. The complexity of the community's sequence samples created new challenges for genome assembly. "It is very important for metagenomic assemblies to rely on high-quality reads," said Alla Lapidus, microbial geneticist at the DOE JGI and co-author on the paper. If some of the sequence is of low quality, she said, it can lead to errors in assembly and gene annotation.

Because of the need for higher quality control, Lapidus said, the DOE JGI developed a new quality control approach that involves a computer tool called LUCY to trim out low-quality sequence in combination with the Paracel Genome Assembler, which appeared to be more appropriate for metagenomic assemblies. This approach was pioneered on the Lake Washington project, Lapidus said, and due to its superior results it is now the standard metagenomic assembly method at the DOE JGI.

"The DOE JGI's unique Integrated Microbial Genomics with Microbiome Samples (IMG/M) data management system was used for detailed annotation, and was instrumental for efficient comparative analysis and metabolic reconstruction of the samples," Lapidus said.

Michael Galperin, a microbial geneticist at the National Centre for Biotechnology Information at the National Institutes of Health, who was not involved in the study, said in an email that the paper describes "an interesting novel approach" and the results "constitute a significant advance in the emerging discipline of metagenomics."

"I think other people can use the same approach in different environments, as long as they have an enrichment technique," Chistoserdova said. "For us this work is just the beginning, because now we will be using this metagenomic sequence as a scaffold for downstream experiments in our lake."

Researchers Develop Customized Immunotherapy to Fight HIV/AIDS

Mon, 18 Aug 2008 12:01:18 +0200

Montreal, Quebec (OBBeC) - A team of researchers led by Dr. Jean-Pierre Routy from the Research Institute of the McGill University Health Centre (MUHC), in collaboration with Dr. Rafick Sékaly from the Université de Montréal, have described how the problem of high genetic variability of the HIV virus can be overcome when creating an AIDS vaccine by designing a personalized immunotherapy for HIV-infected patients.

The team’s findings were presented on August 5 at the XVII International AIDS Conference in Mexico City.

“Our approach is unique in the world: no one else has yet developed customized immunotherapy using the virus from individual patients,” said Dr. Routy. “This experimental technique remains long and costly for the moment, but we’re hoping it will hold the promise of a completely innovative and widely available treatment in the future.”

This immunotherapy is based on the properties of dendritic cells, whose role is to present specific proteins from infectious organisms at their surface, thereby alerting the rest of the immune system. In collaboration with Argos Therapeutics, the researchers designed a study in which the dendritic cells of nine study patients were multiplied in vitro and then treated with the RNA (ribonucleic acid) from the virus that had infected each patient. A virus sample was taken before the administration of any antiretroviral treatment.

The surfaces of these manipulated dendritic cells present an increased number of HIV proteins, which allows them to stimulate the cytotoxic response of a certain type of immune cell called CD8+ lymphocytes. After receiving multiple subcutaneous injections of these dendritic cells, eight of the nine patients involved experienced a significant increase in CD8+ lymphocyte activity.

“At this stage, we have shown that the technique doesn’t cause side effects or an undesirable auto-immune response,” said Dr. Routy. “Health Canada has approved a multicentre clinical trial across the country that will let us further assess the technique's effectiveness at controlling HIV reproduction. We’re hoping that the FDA in the United States will also give us the go-ahead soon so that our pharmaceutical partner, Argos Therapeutics, can begin testing in the United States.”

While more research needs to be done, this new target may lead to an innovative therapeutic approach to fight the AIDS pandemic.

Scientists Develop New Nanotechnology Technique

Fri, 15 Aug 2008 08:50:07 +0200

Wiltshire, UK (OBBeC) - A report from Biotechnology and Biological Sciences research Council (BBSRC) has described how a team led by a BBSRC fellow has made a significant step toward overcoming this major challenge faced by nanotechnology scientists.

In a paper published on 13 August in ChemBioChem, the team from the University of Liverpool, The School of Pharmacy (University of London) and the University of Leeds, described a technique they developed to examine tiny protein molecules called peptides on the surface of a gold nanoparticle. This, according to the team, is the first time scientists have been able to build a detailed picture of self-assembled peptides on a nanoparticle and it offers the promise of new ways to design and manufacture novel materials on the tiniest scale - one of the key aims of nanoscience.

Engineering new materials through assembly of complex, but tiny, components is difficult for scientists. However, nature has become adept at engineering nanoscale building blocks, e.g. proteins and RNA. These are able to form dynamic and efficient nanomachines such as the cell's protein assembly machine (the ribosome) and minute motors used for swimming by bacteria.

The BBSRC-funded team, led by Dr Raphaël Lévy, has borrowed from nature, developing a way of constructing complex nanoscale building blocks through initiating self-assembly of peptides on the surface of a metal nanoparticle. Whilst this approach can provide a massive number and diversity of new materials relatively easily, the challenge is to be able to examine the structure of the material.

Using a chemistry-based approach and computer modelling, Dr Lévy has been able to measure the distance between the peptides where they sit assembled on the gold nanoparticle. The technique exploits the ability to distinguish between two types of connection or 'cross-link' - one that joins different parts of the same molecule (intramolecular), and another that joins together two separate molecules (intermolecular). As two peptides get closer together there is a transition between the two different types of connection. Computer simulations allow the scientists to measure the distance at which this transition occurs, and therefore to apply it as a sort of molecular ruler.

Information obtained through this combination of chemistry and computer molecular dynamics shows that the interactions between peptides leads to a nanoparticle that is relatively organized, but not uniform. This is the first time it has been possible to measure distances between peptides on a nanoparticle and the first time computer simulations have been used to model a single layer of self-assembled peptides.

Dr Lévy said: "As nanotechnology scientists we face a challenge similar to the one faced by structural biologists half a century ago: determining the structure with atomic scale precision of a whole range of nanoscale materials. By using a combination of chemistry and computer simulation we have been able to demonstrate a method by which we can start to see what is going on at the nanoscale.

"If we can understand how peptides self-assemble at the surface of a nanoparticle, we can open up a route towards the design and synthesis of nanoparticles that have complex surfaces. These particles could find applications in the biomedical sciences, for example to deliver drugs to a particular target in the body, or to design sensitive diagnostic tests. In the longer term, these particles could also find applications in new generations of electronic components."

Professor Nigel Brown, BBSRC Director of Science and Technology, said: "Bionanotechnology holds great promise for the future. We may be able to create stronger, lighter and more durable materials, or new medical applications. Basic science and techniques for working at the nanoscale are providing the understanding that will permit future such applications of bionanotechnology."

Mechanism that Controls the Development of Autoimmunity Found

Fri, 15 Aug 2008 08:26:18 +0200

Bethesda, MD (OBBeC) - According to a report from the National Institutes of Health (NIH), scientists at the institute have found a mechanism in the immune systems of mice that can lead to the development of autoimmune disease when turned off.

The findings shed light on the processes that lead to the development of autoimmunity and could also have implications for the development of drugs to increase the immune response in diseases such as cancer and HIV.

The study paper appears online today in the journal Nature.

The scientists from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institute of Allergy and Infectious Diseases (NIAID), both part of the NIH, studied immune system T cells – specifically the helper T cell, an immune system component that helps other cells fight infection. They focused on the protein furin, an enzyme that plays an important role in the functioning of T cells.

Scientists have been limited in their ability to study the protein furin, because other enzymes can perform some of the same functions. Also, furin is essential to life, so scientists have been unable to create a mouse without furin that lives past the embryo stage of development. Since the NIH scientists were unable to see what a mouse without furin would look like, they collaborated with Belgium scientists to create a mouse without furin only in T cells. What they discovered was that mice without furin in these cells developed systemic autoimmune disease. This means that the immune systems of the mice attacked their own cells and tissues throughout their bodies.

"We already know that furin seems to have roles in a variety of human diseases, such as cancer, cystic fibrosis and infectious diseases," says lead author Dr Marko Pesu, in the NIAMS' Molecular Immunology and Inflammation Branch. "These findings show that having no furin in certain immune system cells can increase the immune response and lead to autoimmune disease in mice."

The researchers found that deleting furin in helper T cells affected the functioning of two types of T cells, regulatory and effector T cells. The former cells, also called Tregs, promote immune tolerance to the body's own cells and tissues. Upon further examination, the researchers found that mice lacking furin in Tregs had lower levels of a specific protein, TGF-ß1, which is produced by these cells and is important for their ability to preserve immune tolerance. However, the researchers noted that effector T cells also produce TGF-ß1. They found that furin is also needed for TGF-ß1 production by effector T cells and that the absence of furin in effectors makes these cells more aggressive in causing autoimmune disease and tissue damage.

"Inhibiting furin has been thought to reduce growth of malignant cells or to block infections by preventing essential activation of a pathogen," says study author and NIAMS' Scientific Director Dr John J. O'Shea, chief of the NIAMS' Molecular Immunology and Inflammation Branch. "However, these results suggest that the development of drug interventions could have an unexpected side effect of increasing the risk of developing autoimmune disease."

Scientists Identify Reservoir of Mitochondrial DNA Mutations in Humans

Thu, 14 Aug 2008 12:30:43 +0200

Blacksburg, VA (OBBeC) - Researchers at the University of Newcastle, England, and the Virginia Bioinformatics Institute at Virginia Tech in the United States have revealed a large reservoir of mitochondrial DNA mutations present in the general population.

Clinical analysis of blood samples from almost 3,000 infants born in north Cumbria, England, showed that at least 1 in 200 individuals in the general public harbour mitochondrial DNA mutations that may lead to disease.

The findings, which highlight the need to develop new approaches to prevent the transmission of mitochondrial diseases, were published in The American Journal of Human Genetics.

Mitochondria, the “engines” present in each cell that produce adenosine triphosphate, are passed from mother to offspring. Mutations in mitochondrial DNA inherited from the mother may cause mitochondrial diseases that include muscle weakness, diabetes, stroke, heart failure, or epilepsy.

In almost all mitochondrial diseases caused by mutant mitochondrial DNA, the patient’s cells will contain a mixture of mutant and normal mitochondrial DNA. The proportion of mutant mitochondrial DNA in most cases determines the severity of disease.  Previous estimates from epidemiological studies suggested that mitochondrial diseases affect as many as one person in 5,000.

However, the incidence of new mitochondrial mutations and the prevalence of those carrying these mutations were never fully established due to limitations in the methods used. Most of the earlier estimates of the frequency of mitochondrial DNA mutations in the general population, for example, have depended on identification of clinically affected patients and subsequent retracing of inheritance on the maternal side of the family.

This approach fails to detect the gradual accumulation of mutations in some members of the population, including those individuals who harbour mitochondrial DNA mutations but who otherwise do not show the symptoms of disease.  

Dr. David Samuels, Assistant Professor at the Virginia Bioinformatics Institute and an author on this study, commented: “We know from many clinical studies of patients and their families that our cells can tolerate a rather large amount of mutant mitochondrial DNA with no significant loss of function. From that observation we have suspected that there may be a large number of people in the general population who carry pathogenic mitochondrial DNA mutations, but who are not obviously ill with a mitochondrial disease. This study gives us, for the first time, a measurement of the number of these carriers of pathogenic mitochondrial DNA mutations in the general population. One in every 200 individuals is a lot of people – around 1.5 million people in the United States alone. ”  

The scientists looked at 10 mitochondrial DNA mutations (arising from single nucleotide replacements) often found in patients with mitochondrial disease. By taking advantage of a high-throughput genotyping system that uses mass spectrometry measurements, the researchers were able to detect mutated mitochondrial DNA at high sensitivity. In each positive case, DNA cloning and sequencing were used to confirm the findings. By looking at differences in tissue samples from mother and child, the researchers were also able to estimate the rate at which new DNA mutations had arisen in the population. The incidence of new mutations was close to 100 for every 100, 000 live births.  

Dr. Samuels commented: “These new clinical measurements have given direct evidence for the widespread incidence of pathogenic mitochondrial DNA mutations in the human population. These findings emphasize the pressing need to develop effective ways to interrupt the transmission of these mutations to the next generation.”   

BCC Research Reports on DNA Sequencing Market

Thu, 14 Aug 2008 12:11:06 +0200

Wellesley, MA (OBBeC) - According to a new technical market research report from BCC Research titled “DNA Sequencing: Emerging technologies and Applications,” the global market for DNA sequencing technology was worth $794.0 million in 2007 and an estimated $862.5 million in 2008. This should increase to $1.7 billion by 2013, a compound annual growth rate (CAGR) of 14.7%.  

The market is broken down into the segments of research/drug discovery and development, commercial applications and emerging applications.

Research/drug discovery and development has the largest share of the market, generating $600.4 million in 2007. This is expected to increase to $640.6 million in 2008 and over $1.0 billion in 2013, for a CAGR of 9.7%.   

Commercial applications have the next largest share of the market, worth $193.6 million in 2007 and an estimated $218.8 million in 2008. This should increase at a CAGR of 14.3% to reach $426.1 million in 2013.   

Emerging applications have the smallest but fastest growing share of the market. This sector is expected to generate $3.1 million by the end of 2008 and $272.5 million in 2013, for a CAGR of 144.8%.   DNA sequencing allows us to catalogue the variations within the human genome sequence that make us phenotypically different, and that cause resistance and susceptibility to disease.

The rapidly evolving sequencing technologies provide unprecedented analytical tools that allow us to identify this sequence variation, in humans as well as in other species.   Technology and market forces are working a fundamental shift in the DNA sequencing industry away from stagnant/declining growth towards high growth.

This growth inflection signals the arrival of DNA sequencing as a premier genetic analysis tool: useful for existing applications such as de novo whole genome sequencing and entirely new applications like epigenetic tag sequencing.