Scientists Battle Destructive Bollworm
Sydney Morning Herald (Australia) (08/09/06)

Researchers at Australia's Bio 21 Institute say they need $10 million to determine the genome sequence of the helicoverpa amigera moth. Also known as the cotton bollworm, the moth wreaks havoc on hundreds of crop plants worldwide. Screening the genome would enable scientists to pinpoint genes that lead to pesticide resistance, determine the bollworm's vulnerabilities, and possibly monitor the bollworm's movements. Bio 21 Institute has conducted research in India, reducing insecticide usage by 50 percent, increasing crop yields by 11 percent, and boosting profitability by 75 percent. "We had all the gumboot experience of fighting the bollworm in the field, but not the laboratory back-up we needed, the edge that biotechnology can give us," says Dr. Derek Russell of Bio 21 Institute.
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Diagnoses at the Click of a Mouse
USA Today (08/07/06) Manning, Anita

American medical workers have never seen a case of the bird flu, even though the virus has been around since 1997, so it would be difficult to make a quick diagnosis should someone in the United States contract the disease. However, a new technological tool could remedy that problem, allowing doctors and nurses to differentiate between 40 respiratory diseases and the H5N1 virus. VisualDX, the computer software program part of the Acute Pulmonary Infections program throughout the United States and 10 other countries, provides physicians with instant access to over 13,000 medical photos to help them diagnose over 700 diseases, drug reactions, and infections. Medical staffers key in the symptoms, lab results, and other data to generate side-by-side photos of chest X-rays and in-depth descriptions of bacterial pneumonia, the common flu, and other ailments. Medical specialists in Pennsylvania note that they are already using the system to narrow down diagnoses daily, and officials hope that the system will allow general practitioners to utilize the expertise of medical specialists to speed up diagnoses and contain pandemic-prone diseases before they spread throughout local communities. New York's Elmhurst Hospital Director of Emergency Medicine Stuart Kessler noted that the VisualDX system is on all the computers in the emergency medicine department and on laptops, and the software is backed up onto a hard drive in case Internet connections are lost during an emergency.
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Informatics Sifts Complex MI Data
Diagnostic Imaging (08/01/06) P. 6; Page, Douglas

Medical informatics is crucial to advances in molecular imaging, which involves the collection of data on the molecular level and the creation of images to view changes in gene expression. According to Dr. James Basilion of Case Western University's Center for Molecular Imaging, "The concept of molecular imaging is that we will move away from traditional radiology where differences in tissue density or anatomic changes are used to generate images, and move toward imaging based on biochemisty." Informatics applications will facilitate the identification of disease markers and enable researchers to search through vast amounts of data. Philips Medical Systems CEO Oran Muduroglu notes that "molecular informatics is key to applying sophisticated new diagnostic molecular imaging procedures that are tailored to specific high-risk patients."
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Mining Data for Better Drugs
Drug Discovery & Development (08/01/06) May, Mike

For drug development, data mining can help researchers uncover patterns among large databases of data or track the safety of drugs during the development process, but researchers are unsure that the tool can be used to speed up the development process. However, researchers indicate that data mining can weed out adverse toxicology findings that lead to early termination of drug tests, particularly if historical evidence backs up the adverse finding, and the tool could be used to quickly locate compound names in patents already filed. Most pharmaceutical firms are interested in data mining as a tool to uncover toxicity early-on in human trials or other stages of drug development, according to PerkinElmer Inc. Strategic Collaborations Scientist Scott Kuzdzal. Researchers will have to determine what method of data mining is best, whether structured or unstructured; structured data mining will allow for the quick search through numbers, while unstructured searches will mine data about intellectual property, including drug compounds. However, in some cases, Gene Network Sciences CEO Colin Hill states that researchers are also utilizing the tool to examine processes in an effort to "reverse engineer models from data to determine drug efficacy." However, for drug makers to have successful data mining procedures, firms will first have to "stitch together" their information silos in order to speed up the data mining process, rather than simply search individual silos one-by-one.
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NIST's Goal: Keep Digital Evidence Fresh
Government Computer News (07/31/06) Essex, David

Researchers at the National Institute of Standards and Technology (NIST) are developing new standards for computer forensics, including a library of software programs and tools for testing the reliability of forensics applications. NIST has maintained the National Software Reference Library since 2001. The library now contains CDs for 7,120 software applications. The institute creates a metadata index by running algorithms against the programs to produce digital fingerprints, or hashes. The hashes and metadata index together create the Computer Forensic Reference Data Set (RDS). If during a trial the RDS comes under questioning, NIST could reproduce the hashes to prove its legitimacy. NIST reported in March that it had almost 11 million hashes for three times that many files. The institute is also developing a technique for hashing network files to meet the challenges of the growing evidence that is stored on servers. Another project involves hashes that run on operating blocks, which could prove faster and more precise than black-and-white file hashes. In its Computer Forensics Tool Testing project, NIST is developing standards and methodologies for forensics testing tools, including imaging and hard-drive write protection. Unlike its other work, NIST's computer forensics programs are less driven by industry demands than by what courts will accept as evidence.
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Systems Biology's Clinical Future
Chemical & Engineering News (07/31/06) Vol. 84, No. 31, P. 17; Arnaud, Celia Henry

A number of companies and researchers are working to foster systems biology's evolution from its current status as a research tool to a future in which it is used in clinical applications, with the ultimate goal being "personalized medicine" customized for each individual patient's systems. This would be a move away from the traditional reductionist approach of biological research, although Institute for Systems Biology President Leroy E. Hood says systems biology should not simply be defined by its difference from the traditional approach. Systems biology will be ideally suited to treat diseases that are systems problems themselves, such as "obesity, diabetes, many heart diseases, and hypertension," says Case Western Reserve University School of Medicine's Joseph H. Nadeau. The Massachusetts-based firm Genstruct is aggregating data from various sources to produce cause-and-effect disease models involving all genes, proteins, and metabolites in human cells, dealing "with the complexity of biology at the level of complexity" instead of simplifying things, says CEO Keith O. Elliston. Meanwhile, California-based Entelos is using differential equation-based mathematical modeling to create "virtual patients," which are disease models aimed at helping identify patients best suited for specific drugs and find biomarkers for pinpointing them. Although Entelos is focused on pharmaceutical applications, the virtual-patient concept could be adapted for use in developing personalized medicine--a development journey that will begin with using systems biology to stratify patient populations by their responses to drugs. Two companies working on this problem are Merrimack Pharmaceuticals, which is planning individual patient screening in cancer trials of its protein drugs, and Avalon Pharmaceuticals, which is using RNA-based gene expression technology to identify patients' responses ahead of time. Experts say that moving forward with clinical applications of systems biology will demand analytical technologies that are much more sensitive yet still affordable.
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The Origins and the Future of Microfluidics
Nature (07/27/06) Vol. 442, No. 7101, P. 368; Whitesides, George

Microfluidics, or the manipulation of fluids in channels just tens of micrometers in size, is emerging as a distinct field that could influence fields ranging from IT to optics to chemical synthesis to biological analysis. As the field develops, there are several problems that will need to be addressed using imagination and ingenuity. These include issues of intellectual property, as well as the "first-user premium" under which the first commercial user of a technology assumes a disproportionate amount of cost and risk for its development. In addition, some high-value applications of microfluidics, such as developing home-testing assays or developing new kinds of bioassays for monitoring responses to therapy, will require innovations in biomedicine and microfluidics at the same time. The pharmaceutical industry will need new tools for guiding the development of new drugs, and there are some obvious analytical applications of microfluidics in this realm--such as for monitoring and optimizing the production of protein drugs--as well as more complicated ones such as assays based on primary human cells that could predict clinical trial performance. Some interesting and important potential applications for microfluidics are applications in biomedicine and related areas that require small sample amounts, low cost, and routine operation by untrained staff. Theoretically, the field could make for very high volumes of appropriate analyses, but there is a chicken-or-egg problem: the volumes will be large only if the analysis cost is low and the state of development of the assay is high, but the cost will be low only if the volumes are large. Further development of manufacturing technology is also a key element of the commercial development of microfluidics, so that microfluidic devices can be practically manufactured.
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Automated Protein Purification Methods Combine High-Throughput With High Yield
Medical Imaging Week (07/15/06)

Researchers from the Pacific Northwest National Laboratory and Argonne National Laboratory have devised a pair of "workflows for automated purification of recombinant proteins based on expression of bacterial genes in E. coli," according to their report in Protein Expression and Purification. Chiann-Tso Lin and collaborators describe the first workflow as "a filtration separation protocol in which proteins of interest are expressed in a large volume, 800 mL of E. coli cultures, then isolated by filtration purification using Ni-NTA-Agarose (Qiagen)." The other workflow was "a smaller scale magnetic separation method in which proteins of interest are expressed in a small volume, 25 mL, of E. coli cultures then isolated using a 96-well purification system with MagneHis Ni Agarose (Promega)." According to the researchers, "Both workflows provided comparable advantage yields of proteins, about 8 mcg of purified protein per optical density unit of bacterial culture measured at 600 nm." The researchers' report also discusses the workflows' advantages and limitations as well as optimization strategies.
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Self-Assembling Protein Arrays on DNA Chips Have Been Developed
World Disease Weekly (07/11/06) P. 1079

Researchers Maarten Jongsma and Ralph H.G.M. Litjens at Plant Research International have created self-assembling protein arrays on DNA chips. They accomplished this by auto-labeling fusion proteins with just one DNA address. In a study published in Proteomics, they note that they used "a unique method to attach a single DNA address to proteins in one step during the purification from the E. coli lysate by fusion to human O-6-aklylguanine-DNA-alkyltransferase (SNAP-tag) and the Avitag. Use of the conjugates in converting a DNA chip into a protein chip by self assembly is demonstrated."
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Tiny Technology Becomes a Big Topic
American Medical News (07/10/06) Vol. 29, No. 46, P. 44; Elliott, Victoria Stagg

Having already established itself in several industries, the nanotechnology revolution is making its way into healthcare and is expected to grow exponentially in the few years ahead. Half a dozen medical journals on the topic have been formed, doctors have put together the American Academy of Nanomedicine, the American Medical Association recently had an educational session on the topic, and the National Institutes of Health has funded the creation of nanomedicine institutes at several universities. Generally speaking, nanomedicine is defined by most as using nano-sized particles to target therapeutics and diagnostics at the molecular level. "We're going to intervene on the scale that disease really works as opposed to trying to beat an ant with a baseball bat, which is what we do now," said David Baskin, MD, of Houston's Methodist Hospital Neurological Institute. Two products that have already arisen from nanomedicine research are a burn dressing with silver nanocrystals, from Nucryst Pharmaceuticals, and abraxene, a recently approved drug that delivers the chemotherapy treatment paclitaxel on the back of albumin nanoparticles. Researchers are working on a number of other devices and pharmaceuticals making use of nanotechnology, some of which are entirely new and others of which aim to make existing drugs more effective. In addition, there will be diagnostic applications of nanomedicine in addition to the therapeutic applications; examples include a handheld point-of-care test that uses gold nanoparticles combined with DNA to find markers for neurodegenerative problems, cardiovascular disease, or cancer. Some hospitals are already testing the Biobarcode Ultra-sensitive Protein Detection Technology, to be marketed by Nanosphere, whose co-founder Chad Mirkin believes the test could also be used to detect Alzheimer'smarkers at levels in the blood lower than current assays can detect.
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Protein Initiative Spurs Innovation
Genomics & Proteomics (07/06) Canavan. Neil

The beginnings of the Protein Structure Initiative (PSI) led to the discovery that protein production and crystallization were the major sticking points for those in the field. However, researchers working with these two problems have developed some startling innovations, including the green fluorescent protein (GFP) fusion gel filtration and the chaperone-assisted crystallization. GFP attaches to the C-terminus of peptides, as long as they are right-side-out, and then those fusions are expressed, which helps researchers analyze gel filtration runs according to structural genomics principles. The chaperone-assisted crystallization employs F'ab, a hybridoma-produced fragment of an anticopy11, but researchers indicate that the throughput is not as high as researchers would prefer and the process is time-consuming. Through "evolution in a test tube," proteins will display complimentary determining regions of F'ab fragments on their outer surfaces, with 1010 variants in a single library. However, in order to conduct research on multiple targets through this process, researchers have to reduce the genetic code library, and this is accomplished through observations of the binding process. Protein structure determination can also be discovered via nuclear magnetic resonance, though it is sensitive to protein flexibility and the dynamics of individual proteins' functions. Researchers indicate that this process is also rather slow and time-consuming, but it could be improved through the addition of cryogenic probes and computer methods to turn resonance assignments into 3D structures.
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Automation, Parallelism, and Robotics for Proteomics
Proteomics (06/19/06) Alterovitz, Gil ; Liu, Jonathan ; Chow, Jijun

The evolution of sequencing-automation technology played a key role in the speed at which the human genome project was accomplished. Just as this technology streamlined the previously burdensome process of sequencing, advances in robotics and automation are having a big impact on proteomics. Proteomics' effort to understand and categorize the structure, function, and interaction of proteins makes it a good fit for automation, which tends to seek out economies of scale. Not only are various technologies and methods being used to facilitate automation of proteomics itself, but there are also important efforts aiming at connecting proteomics-based information with other research areas.
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