VATIS Update Biotechnology . Jan-Feb 2010

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Biotechnology Jan-Feb 2010

ISSN: 0971-5622

VATIS Update Biotechnology is published 4 times a year to keep the readers up to date of most of the relevant and latest technological developments and events in the field of Biotechnology. The Update is tailored to policy-makers, industries and technology transfer intermediaries.

Co-publisher: Biotech Consortium India Ltd
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European Union clears GM potato for cultivation

The European Commission has begun a new push to allow farmers in Europe to grow more biotech crops, clearing a genetically modified (GM) potato for cultivation in spite of persistent public opposition to the technology. In the first such step in more than a decade, the commission approved the Amflora potato produced by BASF, a German company, for cultivation inside the 27-country European Union. The potato is engineered to be unusually rich in a starch suitable for making glossy paper and other products, as well as for feeding animals.

The Commission first forwarded an application to grow the potato to governments in May 2004. When a number of countries raised objections, it sent the application to experts at the European Food Safety Authority. The experts approved the application for the potato in 2006 and 2007, and again in 2009. But because member governments were repeatedly unable to reach a qualified majority to approve the potato, the Commission used its power to approve the application.

Currently, the only other biotech crop grown in Europe is a type of corn produced by the United States-based Monsanto and approved in 1998. Along with the GM potato, the Commission also approved three more GM corn varieties developed by Monsanto for food and feed, but those are for import and processing rather than cultivation. For the biotech industry, the decisions handed down by Mr. John Dalli, who took office last month as the blocs Health Commissioner, could signal the emergence of GM products in Europe. Environmentalists, however, have reacted with fury to the decision, saying that Mr. Dalli had overstepped his mandate.

Mr. Dalli also said he would present a proposal this summer to give national governments more authority to decide whether to allow GM crops to be grown within their borders. That could make it easier for some states to go ahead with planting GM products even when other states disapprove of the technology.

China approves GM crops

China has completed its approval of a troika of key biotech crops fibre (Bt cotton), food (Bt rice) and feed (phytase maize). In the latter half of November 2009, Chinas Ministry of Agriculture (MOA) granted two biosafety certificates, and approved biotech Bt rice and biotech phytase maize. The two approvals have major implications for biotech crops in China, Asia and the world.

It is reported that MOA conducted a very careful due diligence study, prior to clearing these two critically important biotech crops for full commercialization in about 2-3 years, pending completion of the standard registration field trials that applies to all new conventional and biotech crops.

According to the International Service for the Acquisition of Agri-biotech Applications (ISAAA), China has successfully planted Bt cotton since 1997 and now, over 7 million small farmers in the country are already increasing their income by approximately US$220 per hectare (equivalent to US$1 billion nationally) due, on average, to 10 per cent increase in yield and 60 per cent reduction in insecticide application. Bt rice offers the potential to generate benefits of US$4 billion annually from an average yield increase of 8 per cent, and 80 per cent decrease in insecticides, equivalent to 17 kg per hectare on Chinas major staple food crop. China, after the United States, is the second largest grower of maize in the world (30 million hectares), used mainly for animal feed. Chinas swine herd, the biggest in the world, increased 100 fold from 5 million in 1968 to over 500 million today. Phytase maize will allow pigs to digest more phosphorus, resulting in faster growth/more efficient meat production.

ACMG against gene patenting and licensing

The American College of Medical Genetics (ACMG) of the United States has a long-standing position that genes are products of nature, and as such should not be patentable. ACMG has provided comments to the Secretarys Advisory Committee on Genetics Health and Society (SACGHS) about its views on an ongoing basis. The recent recommendations of the SACGHS recognize that gene patenting is creating problems both in access to genetic testing and in ensuring the quality of such testing. SACGHS has sought a middle ground that recognizes both the need to protect investments in therapeutic development as well as the need to provide wide access to high-quality genetic testing. It has also noted the lack of evidence that gene patents have contributed to the development of products for the diagnostic laboratory marketplace.

SACGHS has recommended, among other things, that the exemptions from liability for infringement of gene patents afforded to the practice of medicine be extended to gene patents used in diagnostic testing. According to ACMG President, Dr. Bruce Korf, The practice of gene patenting and exclusive licensing has created monopolies that stifle innovation and limit access, exactly the opposite effects that patents are supposed to promote. The SACGHS report is a step towards breaking up this logjam, he said.

Sequencing a Pacific island

Researchers from the University of Florida (UF), the United States, are collecting marine invertebrates on the French Polynesian island of Moorea as part of a massive effort to inventory the DNA sequence of every living species there. The genetic information collected by scientists from UFs Florida Museum of Natural History is part of a whole-system approach that will be used to study ecological processes in depth across the entire island. Mooreas coral reefs in particular are considered crucial indicators of how natural systems respond to climate change.

Nobody has ever sequenced a single place to this level, said Mr. Gustav Paulay, the projects team leader for marine invertebrates and curator of the Florida Museums marine malacology. And nobody has ever investigated coral reef biodiversity this thoroughly in one place. The threeyear Moorea Biocode Project is now in its second year. The Florida Museum scientists are one of seven teams collecting specimens on everything from terrestrial vertebrates to algae. Marine invertebrates make up about 50 per cent of the species on the island, which is about 60 km in circumference and 18 km from Tahiti.

The UF team collects specimens up to three times a day. The catch includes crabs, prawns, plankton, molluscs and worms. The larger specimens all specimens are classified into three sizes: macro (longer than 1 cm), meso (smaller but visible) and micro (less than 1 mm) are then grouped by appearance. The researchers select individual specimens from each grouping to photograph and take tissue samples. The samples are sent to an on-site DNA extractor for immediate preparation, and the DNA is shipped to the Smithsonian Institution for sequencing.

Mr. Paulays team is exploring methods of community DNA extraction. This approach involves running a simultaneous DNA analysis on all the organisms found in a sample, such as sand. Cluster patterns in the DNA sequences will help indicate individual species. Modern technology can sequence millions of genes at once, making the technique possible. DNA information from the project is being uploaded to a global sequencing effort known as the Barcode of Life, which hopes to collect a DNA sequence for every living thing on the planet.

New recombinant proteins feeder facility opened

In Australia, the federal and Victoria state Ministers for Innovation have opened a new Recombinant Proteins Feeder Facility, at Monash University in Melbourne. This A$11.2 million (US$10.2 million) facility will be accessible to Australian scientists who use recombinant proteins for drug discovery and pre-clinical research. The funding for the facility was shared by the Commonwealth Scientific and Industrial Research Organization (CSIRO), the National Collaborative Research Infrastructure Strategy (NCRIS), the Victorian government and Monash University. The centre is meant for the production of recombinant proteins under non- Good Manufacturing Practice (GMP) conditions for pre-clinical trials, with other facilities required for producing proteins under GMP conditions for clinical trials.

Kangaroo enzyme may help prevent skin cancer

A DNA repair enzyme found in kangaroos may help scientists develop a treatment to prevent skin cancer in humans. This repair enzyme does not prevent skin cancer in kangaroos, but does give their skin additional sun protection that humans lack. Some research teams had proposed a dream cream that contains a DNA repair enzyme, which could be applied on the skin after a day in the sun. We are now examining whether this would be feasible by looking at the chemistry behind the DNA repair system, said Ms. Linda Feketeova of Melbourne University (MU), Australia.

Ms. Feketeova and her fellow researchers have been studying the impact that the kangaroo enzyme has on sun-damaged human DNA. We were quite surprised that the DNAs repair process also resulted in a number of chemical byproducts, which have never been seen before, said MU researcher Ms. Uta Willie. Our plan is to study these products to understand if the DNA repair enzyme could be incorporated into a safe and effective method for skin cancer prevention, she added.

Super European Commissioner for biotech

Mr. John Dalli from Malta will be given almost all the important competencies in the area of biotechnology in the next European Commission. Mr. Manuel Barroso, the re-elected Commission President has concentrated a huge array of major responsibilities with Mr. Dalli, who is taking over the liability for the European Medicines Agency (EMEA) and a cosmetics unit from the Directorate- General (DG) for Enterprise & Industry.

The current Maltese Minister for Social Policy will take over all responsibilities for agri-biotechnology together with those related to the European Food Safety Authority (EFSA) from the DG Environment. Further, Mr. Dalli will control the European Unions Plant Variety Office, the European Centre for Disease Control (ECDC), and will take over the competencies for consumer protection, along with those for the Executive Agency for Health and Consumers (EAHC). Mr. Dalli is thought to be a strong supporter of biotechnology, although his country is yet to have a spot on the biotech map. The new Commissioner for Health and Consumer Policy has told the media that the ideal investment for his country should target biotech, pharma or electronics.
Source: www.eurobiotech


Millipore fully acquires joint venture in India

Millipore Corp., the United States, has acquired the remaining 60 per cent ownership of its joint venture in India, Millipore India Pvt. Ltd. The transaction will accelerate strategic growth initiatives in Indias thriving life science market. The revenues of the joint venture a manufacturing, sales and service organization are split evenly between Millipores Bioprocess and Bioscience divisions. The new subsidiary will enable Millipore to invest in initiatives that will drive growth and expand its leadership in the life-science market of India, a critical part of the companys strategy to increase its growth by expanding its presence in Brazil, Russia, India, China and Singapore.

By establishing direct operations in the country, we will be able to more effectively execute our strategy and leverage our unique capabilities to accelerate growth and support our growing customer base in this dynamic market, said Mr. Martin Madaus, Millipore Chairman & CEO.

AstraZeneca strikes deal with Targacept over antidepressant

AstraZeneca, the Anglo-Swedish pharmaceutical group headquartered in the United Kingdom, has announced its biggest deal of the year with a plan to tap into the global market for antidepressants, estimated to be worth more than US$20 billion. The company is teaming up with biotech company Targacept, the United States, which is developing an antidepressant drug that works on the brain in a different way to selective serotonin reuptake inhibitors (SSRIs). Under the terms of the transaction, AstraZeneca will pay Targacept US$200 million, and a further US$1 billion if the medicine gets regulatory clearance and meets certain sales targets. The drug will undergo final clinical trials in 2010 and is expected to be filed with the United States Food and Drug Administration, in 2012.

The licensing agreement means that AstraZeneca will contribute to further development costs and market the drug worldwide, provided it gets regulatory clearance. The deal is significant because the new product could offer a new alternative to two-thirds of patients whose depression fails to respond to SSRIs.

Although there are other options on the market, AstraZeneca is hoping the new product, currently called TC-5214, could prove to be the next blockbuster antidepressant, generating hundreds of millions of dollars for the companys top line. Last September, AstraZeneca announced a similarly designed agreement with Nektar Therapeutics, another United States firm, that involves paying US$125 million upfront for a medicine designed to treat the side-effects of painkillers such as morphine.

Sonic Healthcare continues expansion in the United States

Sonic Healthcare, an international medical diagnostics firm based in Australia, has continued its acquisition spree by taking over East Side Clinical Laboratory in the United States for an undisclosed sum. This is the third laboratory that Sonic acquires in the past four months, and it is expected to purchase more labs in the United States and Germany. East Side, established in 1949, has developed in to a leading provider of clinical and laboratory services in the state of Rhode Island. According to Sonic, Ease Sides annual revenues are over US$30 million.

Genome BC collaborates with Chile and Norway to sequence salmon genome

The economically important and environmentally sensitive Atlantic salmon species will have its genome fully sequenced by an international collaboration involving researchers, funding agencies and industry from Canada, Chile and Norway. Genome BC, Canada, is partnering with the Chiles Economic Development Agency, InnovaChile, Norwegian Research Council and Norwegian Fishery and Aquaculture Industry Research Fund to form the International Cooperation to Sequence the Atlantic Salmon Genome. The Cooperation will invest approximately US$6 million in phase one of the project to produce a genome sequence that identifies and maps all of the genes in the Atlantic salmon genome and can act as a guide/ reference sequence for the genomes of other salmonids (e.g. Pacific salmon, rainbow trout and more distantly related fish such as smelt and pike).

The sequenced genome will be an important public resource that may lead to better management of wild fish stocks, breeding selection for commercially important traits, and elements of food quality, security and traceability. In addition, the fully annotated salmon genome will provide important clues about the impact of cultured fish escapees on wild populations, conservation of fish populations at risk, strategies for combating pathogens, and allow for more accurate assessments of the sustainability of aquatic environments.

Viron patents organ transplant and arthritis drug candidates

Viron Therapeutics Inc., a Canadian biotechnology company pioneering the development of virally derived protein therapeutics, has been granted United States patents related to three of its drug candidates. These patents join a portfolio of more than 80 previously granted patents for Virons multiple therapeutic candidates. Virons unique drug discovery platform identifies proteins expressed by non-human viruses that have evolved over millions of years of evolutionary selection to evade their hosts immune system, endowing them with powerful immuno-modulatory and antiinflammatory properties.

The new patents cover three therapeutic candidates VT-111, VT-346 and VT-384. One patent pertains to the treatment of chronic transplant rejection by administering VT-111 in combination with an immunosuppressant, such as cyclosporine. Virons second therapeutic candidate, VT- 346, is a powerful inhibitor of TNF-a. In head to head testing, VT-346 has proven itself to be as much as 100 times more potent than some currently marketed therapeutics. The patent covers the use of VT-346 in treating immuno-modulatory disorders characterized by inflammation, such as rheumatoid arthritis, transplant rejection, asthma and inflammatory bowel disease. VT-384, a protein derived from the Yatapoxvirus that targets IL-18, a cytokine expressed at sites of chronic inflammation. This cytokine has been implicated in many autoimmune diseases and a variety of cancers.

Celgene buys Gloucester Pharma

In the United States, the international biotechnology company Celgene Corp. is buying privately held Gloucester Pharmaceuticals Inc. for US$640 million, getting access to key cancer drugs. The deal includes US$340 million in cash and US$300 million in future regulatory milestone payments.

Gloucester develops drugs for blood cancers with limited treatment options. Its drug Istodax was recently approved by the Food and Drug Administration for cutaneous T-cell lymphoma treatment. Gloucester is seeking other approvals, and European regulators are reviewing Istodax. The company is testing drugs for cutaneous T-cell lymphoma and peripheral T-cell lymphoma. It is also developing combinations of drugs for solid tumors and for multiple myeloma.

Celgenes drugs include: Revlimid, used against multiple myeloma, non-Hodgkins lymphoma and chronic lymphocytic leukemia; and Vidaza, which is approved for treatment of the bone marrow disease myelodysplastic syndrome and acute myeloid leukaemia.

Sword Diagnostics patents immunodetection technology

Sword Diagnostics Inc., the United States, has secured United States patent on Method and Apparatus for Detection of Biological Organisms using Raman Scattering, which covers the core technology that focuses on improved sensitivity.

Sword markets its technology for biomarker measurement for drug discovery and academic life science researchers, and will partner to develop clinical diagnostics assays. The technical solution is an immunoassay detection system that employs Raman spectroscopy and a proprietary chemistry. It extends the sensitivity over current detection technologies and is easily incorporated into assays that use a peroxidase-based detection system.


Microbes genetically modified to make biofuels

In the United States, some ambitious scientists and entrepreneurs are using genetic engineering to produce fuel straight out of tiny plants and microbes. In one of its labs, Joule Biotechnologies is testing the process called direct solar liquid energy. The converters used in the process are tabletop-sized rectangular, plastic frames; each with dozens of clear, skinny tubes running their length. Each tube is filled with a greenish liquid, the greenish colour coming from the tiny, genetically modified organisms. The bubbles produced in the liquid are carbon dioxide (CO2).

One engineered organism makes ethanol, while another makes diesel fuel. Exposed to sunlight and soaking up CO2 from a power plant, the converters would send a constant stream of fuel-laden water to a separation facility. An acre of the solar converters could produce many times what biofuel crops do. There is no intermediary like algae that has to be grown or cellulose to be processed, and the process does not require fresh water. The process cost-effectively converts sunlight and CO2 to liquid fuels.

Biochemistry Professor Larry Wackett leads a team at the University of Minnesota that is taking a different approach to direct solar fuels. According to Prof. Wackett, no matter how much you modify an organism, you can only teach it so many tricks. If you try to engineer that organism to do many additional things, it puts stress on it and it is often very difficult to highly engineer that to do all of the things that you want. Prof. Wackett is working on a bacterial buddy system.

He takes, for example, a photosynthetic organism such as a genetically modified cyanobacteria, called Shewanella, which is good at churning out the building blocks of hydrocarbon fuels and links it up with another organism that will take the energy (carbon) from the photosynthetic organism and convert that into a hydrocarbon. The Minnesota lab has spun out a company, BioCee, which has proved at the bench-scale that the technology really works.

Carbon nanotubes for highspeed genetic sequencing

Mr. Stuart Lindsay, Director of the Centre for Single Molecule Biophysics at the Biodesign Institute of Arizona State University, the United States, along with his colleagues, has demonstrated the potential of a method in which a single-stranded ribbon of DNA is threaded through a carbon nanotube, producing voltage spikes that provide information about the passage of DNA bases as they pass through the tube a process known as translocation. The method speeds up the otherwise slow process of DNA sequencing. The new approach involves the use of nanopores orifices of molecular diameter that connect two fluid reservoirs. A constant voltage can be applied between two electrodes located at either end of the nanopore, inducing an ionic current to flow through the length of the nanopores enclosed channel. At this scale, the passage of even a single molecule through the pore generates a detectable change in the flow of ionic current, which is electronically amplified and measured.

In the current study, single-walled carbon nanotubes, 1-2 nm in diameter, were used for the conducting channels. A current induced through the nanotube draws segments of single-stranded DNA (oligomeres), comprising either 60 or 120 nucleotides, into the opening of the nanotube and translocates them from the anode side of the nanotube to the output cathode side, due to the negative charge carried by the DNA molecule. The velocity of DNA translocation is dependent on both the nucleotide structure and molecular weight of the DNA sample. Among the successfully formed nanotubes, a sharp spike in electrical activity is detected during the process of DNA translocation. Reversing the electrode bias causes the current spikes to disappear, and restores the original bias that causes the spikes to reappear.

Mr. Lindsay stresses that the transient current pulses, each containing roughly 10 7 charges, represent an enormous amplification of the translocated charge. Quantitative polymerase chain reaction was utilized to verify that the particular carbon nanotubes displaying these anomalously sharp current spikes around 20 per cent of the total sample, were indeed those through which DNA translocation had occurred.

Observation of current-voltage curves registered at varying ionic concentrations showed that ion movement through some of the tubes is very unusual, though understanding the exact mechanism by which DNA translocation gives rise to current spikes will require further modelling. Critical to successful rapid sequencing through nanopores is the precise control of DNA translocation. The hope is that genetic reading can be significantly accelerated, while still allowing enough time for DNA bases to be identified by electrical current traces. If the process can be perfected, Mr. Lindsay emphasizes, DNA sequencing could be carried out thousands of times faster than possible currently, that too at a fraction of the cost.

New finding on causes of severe obesity in childhood

In the United Kingdom, scientists have discovered that the loss of a key segment of DNA can lead to severe childhood obesity. This is the first study to show that such genetic alteration can cause obesity. The study, led by Dr. Sadaf Farooqi from the University of Cambridge and Dr. Matt Hurles from the Wellcome Trust Sanger Institute, looked at 300 children with severe obesity. The team scanned each childs entire genome looking for types of mutation known as copy number variants (CNVs) large chunks of DNA either duplicated or deleted from our genes as such mutations may play an important role in genetic diseases.

By looking for CNVs that were unique in children with severe obesity, compared with over 7,000 controls, they found that certain parts of the genome were missing in some patients with severe obesity. According to Dr. Farooqi: Our results suggest that one particular gene on chromosome 16 called SH2B1 plays a key role in regulating weight and also in handling blood sugar levels. People with deletions involving this gene had a strong drive to eat and gained weight very easily.

This study shows that severe obesity is a serious medical issue that deserves scientific investigation, says Dr. Farooqi. It adds to the growing weight of evidence that a wide range of genetic variants can produce a strong drive to eat. We hope that this will alter attitudes and practices among those with professional responsibility for the health and well-being of children. The study proves that, although the increased prevalence of obesity over the past 30 years is undoubtedly driven by environmental factors, genetic factors play a major role in determining why some people are more likely to gain weight than others.

DNA molecules in moss open door to new biotechnology

Researchers from Uppsala University in Sweden have demonstrated that plasmid-based genetic technology methods, which had been limited to single-cell organisms such as bacteria and yeasts, can be extended to mosses, opening the door to applications of a number of powerful techniques in plant research. Prof. Hans Ronnes research team at the Department of Medical Biochemistry and Microbiology worked with Physcomitrella moss, which is widely used in research because its genes are easier to knock out than those of other plants. Previous work had shown that DNA introduced into Physcomitrella cells is capable of self-replication through an as yet uncharacterized process.

The new study, which was led by Dr. Eva Murn and Ph.D. student Mr. Anders Nilsson, shows that plasmids introduced into moss cells can be restored to bacteria without affecting the plasmids original structures, subject to certain conditions are met. Up to now, various kinds of rearrangements have sharply limited the use of plasmids in plantand animal-cell research. Our work with plasmids in moss suggests that it will be possible to use powerful methods such as gene cloning by complementation and overexpression directly in plant cells without recourse to single-cell organisms like bacteria or yeasts, says Prof. Hans Ronne. This is expected to simplify basic and applied biotechnology research on plants.

Tumour-suppressor gene linked to liver cancer

Researchers from the National Human Genome Centre, China, have identified the scavenger receptor SCARA5 as a candidate tumour suppressor gene in human hepatocellular carcinoma (HCC). Their study reports that SCARA5 protein downregulation as a result of SCARA5 genetic loss and epigenetic silencing can contribute to HCC tumour development and progression.

Analysis of HCC tissue samples indicated that SCARA5 was frequently subjected to genetic loss and epigenetic silencing. The researchers also observed that SCARA5 protein downregulation was most marked in HCC tissue samples characterized by tumour invasion into the blood vessels a sign of aggressive disease. Furthermore, SCARA5 knock-down via RNAi markedly enhanced HCC growth in vitro, colony formation in soft agar, as well as invasiveness, tumourigenicity, and lung metastasis in vivo. By contrast, SCARA5 overexpression suppressed these malignant behaviours. Further analysis in HCC cells lines in vitro and after xenotransplantation into mice were consistent with SCARA5 being a tumour suppressor gene.

Genetic protection from TB

A study involving 128 South African families has identified genetic traits that may protect some people from tuberculosis (TB) in a finding that could help lead to a new TB vaccine. The study could help reveal mechanisms behind natural resistance against TB infection. To be infected or uninfected is a characteristic of individuals and therefore can be manipulated to prevent infection, said Mr. Erwin Schurr, a molecular geneticist at the McGill University in Canada who led the study. There are, in fact, big advantages because if it is in your genome, it means these are factors you can identify. Once you identify them, you can target them in people who are actually prone to infection, Mr. Schurr explained.

The Bacille Calmette-Guerin (BCG) vaccine to prevent TB has been around since 1919 but it gives only some measure of protection for children and does not protect adults. Therefore, a better vaccine is needed against Mycobacterium tuberculosis, the bacterium that typically attacks the lungs and causes TB.

Mr. Schurr and his colleagues studied 128 families 186 parents and 350 offspring living in two Cape Town suburbs with high TB prevalence. None in the families was sick with TB, but some were infected by the TB bacterium. Among the children, the researchers found that about 40 per cent were uninfected by the bacterium. A study of the genes of the people led the scientists to detect genetic patterns among children who were infected with TB and those who were not, particularly relating to two specific chromosomes. We found chromosome 11 and chromosome 5 that were enriched in particular children (who were uninfected), Mr. Schurr said. The researchers will clone the genes that appear to provide protection, then do studies to try to figure out how the genes led to the resistance. The team hopes the findings can lead to a better vaccine.

Genetic link to heart failure

A team of researchers at Washington University School of Medicine, St Louis, the United States, has identified a group of 12 genetic variants in the HSPB7 gene that is associated with heart failure in humans. The team, led by Mr. Gerald Dorn, used an approach they developed, which allows ultra-high-throughput targeted DNA sequencing to identify genetic variation in four genes with biological relevance to heart failure. They identified in a large group of Caucasian individuals with heart failure, 129 separate genetic variants in the four genes, including 23 that appeared novel. Further analysis of 1,117 Caucasian individuals with heart failure and 625 unaffected Caucasians indicated that a block of 12 genetic variants in the HSPB7 gene was associated with heart failure. Confirmation of this association was provided by analysis of an independent group of individuals. The scientists hope to use the same approach to identify further genetic variants associated with heart failure, a disease influenced by multiple genetic factors.
Source: www.medical


Proteins show promise for ovarian cancer screening

Elevated levels of three proteins show ovarian cancer is starting to grow years before women are diagnosed, but they do not increase soon enough to be an early indicator of the disease, researchers in the United States said. In a large clinical trial, the researchers analysed the blood samples and identified 34 women with ovarian cancer along with a control group of 70 women who did not have cancer. Their blood samples were used to evaluate six proteins identified as potential indicators of ovarian cancers. Levels of three of the proteins began to increase slightly in ovarian cancer patients three years before diagnosis but did not reach a level that can be detected in a screening programme, according to the lead author Dr. Garnet Anderson of the Fred Hutchinson Cancer Research Centre.

Researchers seeking to a screening programme to detect ovarian cancer are looking for something similar to the prostate-specific antigen (PSA) for prostate cancer, Dr. Anderson said. PSA is a protein monitored for early detection of prostate cancer in men. Wed like that for ovarian cancer because it is clear that women who are detected at the stage where the disease is still confined to the ovaries do very well. Their prognosis is excellent, she said. CA125, which is one of the markers we looked at, is the best biomarker that has been identified to date and our study confirms that and this prediagnostic period as well. But it is not sufficiently accurate.

Light on mechanism of invasion protein

When infecting humans, bacteria invade cells, migrate through the body, avoid immune response and misuse processes of the host cell for their own purposes. To this end, every bacterium uses its own strategy. In collaboration with a research group in the United Kingdom, structural biologists from the Helmholtz Centre for Infection Research, Germany, and the University of Bielefeld, Germany, have elucidated one such mechanism of Listeria.

Two invasion proteins are crucial for infection. Each binds a specific receptor on the surface of human cells, which stimulates the host cell to take up the pathogen. Normally, these receptor molecules exert a different function; for example, the regulation of cell growth and wound healing. One of the sources for Listeria infections is spoiled meat, leading to listeriosis. Firstly, the pathogen breaches the intestinal barrier to enter the body. The key for further spreading is the invasion protein internalin B that is located on the bacterial surface. On human cells, internalin B activates a receptor molecule called Met, thereby signalling the host cell to take up the pathogen. Inside the cell, Listeria uses the host cells nutrients and is sheltered from an immune response.

Until now, the researchers did not know how the bacterial invasion protein activates the human receptor. To solve this question, the researchers first analysed the crystal structures of the single internalin B molecule and of its complex bound to human Met. In X-Ray structural analysis we noticed that in protein crystals two internalin B molecules align characteristically, reports Mr. Hartmut Niemann, an assistant professor at the University of Bielefeld. Prof. Dirk Heinz, head of structural biology at Helmholtz Centre, adds: This gave rise to the idea of a dimer two congregated internalin B molecules playing a pivotal role in the activation of the Met receptor.

Minor changes in the internalin B molecule confirmed their hypothesis: inhibiting the congregation of two internalin B molecules prevented the activation of Met. On the other hand, strengthening the interaction resulted in very strong receptor activation. These results may lead to the development of new protein drugs in the future.

New diagnostic biomarker for heart attacks

In a new study, researchers at Kings College London, the United Kingdom, have identified cardiac myosin-binding protein C (cMyBP-C) as a potential diagnostic biomarker for heart attacks, one that may be particularly valuable for mild attacks in which traditional diagnostic proteins may not be abundant enough. Currently, one of the gold-standards for diagnosis of heart attacks, or acute myocardial infarctions, is scanning for the presence of the proteins troponin I and troponin T, as they are produced specifically in the heart and are almost completely absent in the blood in healthy individuals. However, troponins are not ideal markers, since they are released somewhat slowly following a heart attack (peaking around 18 hours post-infarction) and remain in the blood for up to 10 days afterwards, hindering the diagnosis of any secondary heart attacks.

In the quest for better biomarkers, the researchers performed a proteomic analysis of all the proteins released by mouse hearts following induced heart attacks. They identified 320 proteins not released by normal hearts, including all the currently employed biomarkers. Only a handful of these proteins were specific to the heart. But among those, one very promising lead was cMyBP-C; within 5 minutes following a heart attack it became nearly 20 fold more abundant than before, one of the highest increases of all 320 identified proteins. In fact, it was abundant following even minor heart attacks, suggesting it could be very useful in such instances.

Synthetic protein mimics metalloproteins functions

Scientists have designed a synthetic protein that is both a structural model and a functional model of a native protein, nitric-oxide reductase. The designed protein provides an excellent model system for studying nitric-oxide reductase, and for creating biocatalysts for biotechnological, environmental and pharmaceutical applications, said Dr. Yi Lu, chemistry professor at University of Illinois, the United States, who directed the work.

Dr. Lus research group and collaborators at Brookhaven National Laboratory are among the first to design a protein that mimics both the structure and the function of a metalloprotein. Nitric-oxide reductase is a key enzyme in the nitrogen cycle that is critical for life. Nitric oxide plays a key role in cell signalling and host-pathogen responses. Therefore, study of nitric-oxide reductase is an important step towards understanding these physiological and pathological processes.

However, it has been difficult to study nitric-oxide reductase, as it is a membrane protein that is not water soluble. To mimic the structure and function of nitric-oxide reductase, the researchers began with myoglobin, a small muscle protein. Although smaller than nitric-oxide reductase and watersoluble, myoglobin can reproduce major features of the native system. Into this scaffold protein the researchers engineered a new iron binding site consisting of three histidines and one glutamate.

In addition to their structural roles, the histidines and glutamate in the active site may also provide the two protons required for nitric oxide reduction. The designed protein models both the structure and the function of nitric-oxide reductase, and offers additional insight that the active site glutamate is required for both iron binding and reduction activity, Dr. Lu said. The designed protein also serves as an excellent model for further mechanistic studies of nitric-oxide reductase.

New technique detects age-related proteins

Chemists and biologists from the University of Bath, the United Kingdom, have developed a new technique that could be used to diagnose and develop treatments for age-related conditions like Alzheimers disease, diabetes and cancer. In these diseases, proteins in the body react with sugars in a process called glycation, modifying the proteins function. This can trigger complications such as inflammation and premature aging. The team at Bath, led by Dr. Jean van den Elsen and Dr. Tony James, has developed a technique that can detect glycated proteins and could in the future be used for diagnosing a whole range of diseases in patients.

For this study, the researchers patented a new type of gel electrophoresis, which uses boronic acid to distinguish between the glycated and unmodified proteins. The Bath method specifically recognises bad sugars in the presence of good sugars and as such is an excellent diagnostic tool. The method could aid the development of new drug-based therapies for age-related diseases.

While the technique has only been assessed in the lab at present, the researchers say it has the potential to be developed into a test for these conditions in patients.


Scientists gain new insight into disease-causing bacteria

In the United States, a team of scientists from The Forsyth Institute, the University of Connecticut Health Centre, the Wadsworth Centre and the Centres for Disease Control and Prevention (CDC) have used state-of-the-art technology to elucidate the molecular architecture of Treponema pallidum, the bacterium that causes syphilis. The previously unknown detailed structure of the bacteria can now be shown in three dimensions. This provides the first real image of the pathogen and reveals previously unknown features, which may help fight the spread of syphilis.

Using cryo-electron tomography (CET) a type of microscope used to obtain a three-dimensional reconstruction of a sample from two dimensional images at extremely low temperatures the team of researchers has clarified the fundamental differences between T. pallidum and other gramnegative bacteria. According to lead author Dr. Jacques Izard, this work provides a clear snapshot of a cell in real time. This changes how we study this bacterium. Having an accurate architecture of the cell provides important insight for understanding how it becomes invasive in the human body. With this information we may learn how to stop disease progression.

With CET, T. pallidum cells appeared to form flat waves and did not contain an outer coat. This highly motile organism can attach to human cells by its tip. The present work has shown that the tip of this bacteria has a unique structure among pathogens, which improved the understanding of cell attachment and tissue penetration. Additionally, novel structural evidence explains how those bacteria mysteriously move with the flagella inside their cell body.

The molecular basis of cardiovascular disease

In the United States, researchers led by Dr. Daniel Chasman at Brigham and Womens Hospital and Harvard Medical School in Boston, the Framingham Heart Study, and the PROCARDIS consortium in Stockholm, Sweden and Oxford, the United Kingdom, performed genetic association analyses across the whole genome of 17,296 women of European ancestry from the Womens Genome Health Study. This large scale analysis of the effects of common genetic variation on plasma lipoprotein profile, a critical component of cardiovascular risk, identified 43 genetic loci contributing to lipoprotein metabolism, including 10 loci not previously recognized in other whole genome analyses.

The findings were validated among additional populations of both men and women. The research also quantified the contribution of common genetic variation to the concentration of plasma lipoproteins according to class low-density lipoprotein (LDL), high-density lipoprotein (HDL) or very low density lipoprotein (VLDL) as well as size and cholesterol or triglyceride content. The balance of LDL, HDL, and VLDL particle concentration is a definite measure of cardiovascular risk. These major classes of lipoprotein particles are composed of sub-species that can be categorized according to size. While the overall concentration of each of the major classes can be estimated by the clinical measures of LDL-cholesterol, HDLcholesterol and triglycerides, the determinations of the concentration of the sub-species by nuclear magnetic resonance spectroscopy (NMR) in the current study provide a more precise picture of lipoprotein profile.

Small nanoparticles bring big improvement to medical imaging

A joint research team, working at the National Institute of Standards and Technology (NIST) and the National Institute of Allergy and Infectious Diseases (NIAID), the United States, has discovered a method of using nanoparticles to illuminate the cellular interior to reveal the molecular-scale, slow processes. Quantum dot, a type of nanoparticle, glows when exposed to light. These semiconductor particles can be coated with organic materials, which are tailored to be attracted to specific proteins within the part of a cell a scientist wants to examine.

Quantum dots last longer than many organic dyes and fluorescent proteins that we previously used to illuminate the interiors of cells, says biophysicist Mr. Jeeseong Hwang, who led the team on the NIST side. They also have the advantage of monitoring changes in cellular processes while most high-resolution techniques such as electron microscopy only provide images of cellular processes frozen at one moment. Using quantum dots, cellular processes involving the dynamic motions of proteins can be elucidated.

The team focused primarily on characterizing quantum dot properties, contrasting them with other imaging techniques. In one example, they used quantum dots designed to target a specific type of human red blood cell protein that forms part of a network structure in the cells inner membrane. When these proteins cluster together in a healthy cell, the network provides mechanical flexibility to the cell so it can squeeze through narrow capillaries and other tight spaces. But when the cell is infected with the malaria parasite, the structure of the network protein changes.

Examination of the clustering mechanism with the dots revealed that as the membrane proteins bunch up, the quantum dots attached to them are induced to cluster themselves and glow more brightly, aiding scientists to watch as the clustering of proteins progresses. The team found that when quantum dots attach themselves to other nanomaterials, the dots optical properties change in unique ways in each case. It also found evidence that these optical properties are altered as the nanoscale environment changes, offering greater possibility of using quantum dots to sense the local biochemical environment inside cells.

New research shows versatility of amniotic fluid stem cells

For the first time, scientists have shown that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought. Writing in Oncogene, the research teams of Dr. Anthony Atala, Director of Wake Forest Institute for Regenerative Medicine, the United States, and Dr. Markus Hengstchlger, from the Medical University of Vienna, Austria, have shown that these amnion stem cells can form embryoid bodies (EBs), the three-dimensional cell aggregates that can be directed to become virtually any cell in the body.

Dr. Atalas team is currently evaluating the cells for their potential to treat diabetes and kidney disease. The current research is one of several projects designed to determine the potential of this new type of stem cell. For the study, scientists generated two additional lines of stem cells from amniotic fluid. They then investigated the incidence of EB formation in all three lines, and found that human amnion stem cells can indeed form EBs.

The scientists also identified a protein found inside cells, mTOR, as the regulator of EB formation. Dr. Hengstshlger, whose team was the first to provide evidence for the existence of stem cells in amniotic fluid, said that this finding may allow for new insights into the molecular mechanism of EB formation. He said the cells may be a useful source for generating disease-specific stem cell lines for studying the differentiation process to determine what goes wrong in genetic diseases.

Stem cell technology treatment for bone fractures

A novel technology involving use of stem cells developed at the Hebrew University of Jerusalem, Israel has been applied to provide better and rapid healing for patients suffering from complicated bone fractures. The technology, involving isolation of the stem cells from bone marrow, was developed by Dr. Zulma Gazit, Dr. Gadi Pelled, Prof. Dan Gazit and their research team at the Skeletal Biotechnology Laboratory at the Hebrew University. The technology has now successfully been used to treat complicated fractures in seven patients at the Hadassah University Hospital in Ein Kerem, Jerusalem.

In recent years, the use of mesenchymal stem cells (MSCs, or multipotent stem cells that can differentiate into a variety of cell types) has been claimed to be a promising biological therapy that could be used to treat complicated fractures and other disorders in the bone, cartilage, tendon, intervertebral discs and even the heart muscle. MSCs form a unique population of adult stem cells that can readily be isolated from various sites in the human body, especially from bone marrow and adipose (fat) tissues. But the conventional method of MSC isolation is laborious, costly and also possibly injurious to the therapeutic quality of the cells. Therefore, an alternative method involving the immediate use of these stem cells was needed.

Now, the Hebrew University group has developed a technology called immuno-isolation in which MSCs are sorted out from the other cells residing in a bone marrow sample, using a specific antibody. The immuno-isolated cells could be used immediately to form new bone tissue when implanted in laboratory animals, without having to undergo a prolonged incubator growth period.

A clinical trial has been initiated, to establish the foundation for the use of immuno-isolated MSCs in orthopaedic surgery. To date, seven patients suffering from complicated fractures have been treated successfully with a combination of their own immuno-isolated MSCs and blood products.

Whole chromosome changes proved to cause cancer

Researchers from Mayo Clinic, the United States, have proven the longstanding theory that changes in the number of whole chromosomes called aneuploidy can cause cancer by eliminating tumour suppressor genes. Their findings end a major controversy in the field of cancer research as to whether aneuploidy is a cause or a consequence of cancer.

Virtually all human cancers have an abnormal number of chromosomes. Therefore, it has been long suspected that gene mutations that promote erroneous chromosome separation during cell division are to blame for tumour development. By using a combination of new and established mouse models for human cancer, we were able to prove that aneuploidy causes cancer and elucidate the mechanism by which it does so, says Dr. Jan van Deursen, senior author of the study. These findings explain how chromosomal errors can cause cancer. They prove the role of aneuploidy in the elimination of genes that suppress tumour formation.


How a genetic symphony affects plant development

In a recent research report, scientists at the Plant Gene Expression Centre of the United States Department of Agriculture show how a family of genes (1-aminocyclopropane-1-carboxylate synthase, or ACS genes) are responsible for production of ethylene. Since this gas affects many aspects of plant development, this information forms the foundation for future genetic manipulation that could make plants disease resistant, able to survive and thrive in difficult terrain, increase yields, and other useful agronomical outcomes. This discovery was made with the weed Arabidopsis thaliana, but it will be applicable to edible crops.

To understand the function and regulatory roles of each ACS gene in ethylene production during plant development, scientists from the laboratory of Dr. Athanasios Theologis analysed the essential and non-essential roles of each of the family of A. thaliana ACS genes. They found that while loss of any single ACS gene had no visible effect on the plant, it did affect the activity of other genes in the family. They grew different plants that had different combinations of these genes turned on and turned off, and found that the members of this gene family have different but overlapping functions in plant development, such as growth, flowering time, gravitostimulation and disease resistance.

New map of variation in maize genetics

A new study of maize has identified thousands of diverse genes in genetically inaccessible portions of the genome. New techniques may allow breeders and researchers to use this genetic variation to identify desirable traits and create new varieties that were not easily possible before. The researchers from the United States have identified the first map of haplotypes sets of closely linked gene variants known as alleles in the maize genome. They have identified and mapped several million allele variants among 27 diverse inbred maize lines. The haplotype map will help develop molecular markers and tools that breeders and geneticists around the world can use to study maize and improve maize varieties, said Dr. Ed Buckler, the papers senior author, a research geneticist in the Institute for Genomic Diversity and an adjunct professor of plant breeding and genetics at the Cornell University. Mr. Michael Gore, a graduate student in Dr. Bucklers lab, is the papers lead author. Other co-authors are affiliated with the United States Department of Agricultures Agricultural Research Service (ARS), Cold Spring Harbour Laboratory, and University of California-Davis.

In the last century, maize breeders have found limitations in recombination, where large regions genetic material fail to recombine near the chromosomes centre, called the centromere. The breeders overcome this by crossing two complementary lines, resulting in a new line with higher yields and vigour. However, as large regions of the maize chromosome are less accessible, they cannot arrive at optimal genetic combinations. The study has revealed a great deal of genetic variation near the chromosomes centromeres, which resist recombining. Now, breeders can use molecular markers to identify desirable genetic variants and new genetic technologies to move the desired variation onto the same chromosomes and create new, more productive lines with desired traits. The study revealed more than 100 large regions (selective sweeps) on the genome where breeders selected for a gene during domestication. In doing so, genetic diversity was lost around those genes.

Precision breeding creates super potato

For the first time in the history of the Emsland Group the largest German potato starch manufacturer it processed Tilling potatoes, which exclusively contain amylopectin starch. Besides extracting nutritional starches for edible purposes, it can also be used for paste and smooth coating for paper and thread production.

Targeting Induced Local Lesions in Genomes or Tilling is a breeding process that researchers want to use to push evolution yet another step forward. In nature, evolution proceeds slowly: through mutation and selection, plants and animal species adapt and change. Over the course of generations, those species develop that, due to their genetic make-up, are best adapted to the prevailing environmental conditions. Others just die out. Modern breeding processes operate the same way, though the natural mutation rate is accelerated. With the aid of chemicals, a vast number of mutants can be rapidly obtained, says Jost Muth of Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), who participated in the development of the new potato led by Dr. Dirk Prfer of IME.

In Dr. Prfers laboratory, the mutated seeds were germinated. As soon as the first leaves appear, it is harvest time: the researchers take a leaf sample, break apart the cellular structure, isolate the genome and analyse it. This way, they can find out within a few weeks if a mutation has attained the desired traits.

In another project, IME researchers, in collaboration with the companies Emslandstrke and Bioplant, found the super potato germ, after examining 2,748 seedlings, that exclusively produces the starch component amylopectin. From this germ, experts were able to generate the first generation of super potatoes. There are genes active in their genome responsible for the formation of amylopectin, whereas genes that trigger the formation of amylose are shut off.

Biotech crops promote improved sustainability

According to several research summaries released by PG Economics, the impacts of biotechnology on agricultural production are significant. Biotech crops have contributed to significantly reducing the release of greenhouse gas (GHG) emissions from agricultural practices. In 2007, this was equivalent to removing 14.2 billion kilograms of carbon dioxide from the atmosphere or removing nearly 6.3 million cars from the road for one year. GHG emission reductions are derived from two principle sources: reduced fuel use from lessfrequent herbicide or insecticide applications and reduced energy usage in soil cultivation from the use of no-till and reduced-till farming systems. From 1996 to 2007, pesticide spraying reduced by 359 million kilograms, which is equivalent to 125 per cent of the annual volume of pesticide active ingredient applied to arable crops in the European Union.

The fuel savings associated with making fewer spray runs (relative to conventional crops) and the switch to conservation, reduced-till and notill farming systems have resulted in permanent savings in carbon dioxide emissions. In 2007, this amounted to about 1.144 billion kilograms (attributable to reduced fuel use of 416 million litres). From 1996 to 2007, the cumulative permanent reduction from fuel use was estimated at 7.09 billion kilograms of carbon dioxide (arising from reduced fuel use of 2.578 billion litres).

The use of no-till and reduced-till farming systems has increased significantly with the adoption of herbicide-tolerant biotech crops because the technology has improved growers ability to control competing weeds, which reduces reliance on soil cultivation and seed-bed preparation as a means for getting good levels of weed control. As a result, tractor fuel use for tillage has dropped, soil quality has enhanced and levels of soil erosion have reduced. Thus, more carbon remains in the soil, leading to lower GHG emissions.

Based on savings arising from the rapid adoption of no-till and reduced-till farming systems in North and South America, an estimated extra 3.57 billion kilograms of soil carbon were sequestered in 2007 (equivalent to 13.103 billion kilograms of carbon dioxide that have not been released into the atmosphere). Cumulatively, the amount of carbon sequestered is probably higher due to year-over-year benefits to soil quality.

Farmers rely on a sustainable environment to continue farming. Biotechnology is an important tool that has helped agriculture make great strides in improving its environmental footprint. Pesticide use on four crops in the countries where biotech crops have been planted has fallen 359 million kilograms (down 8.8 per cent), resulting in a larger 17.2 per cent reduction in the associated environmental impact, according to PG Economics. Farmers recognise that improving the environment also helps their bottom line. A new tool, Field to Markets Fieldprint Calculator, lets farmers input information about their production practices so they can then view their environmental footprint.


Desert Plants: Biology and Biotechnology

The life-supporting vegetation of deserts is characterized by its unique metabolism, reproductive biology and adaptive characters. Plants such as Prosopis cineraria and date palm form the basis of the rural economy in many countries; Jojoba and Jatropha are of interest as non-conventional sources of industrial oil and biodiesel. Desert Plants: Biology and Biotechnology covers seed biology, reproduction, mycorrhizae, stress physiology and metabolism of desert plants, besides describing current biotechnological approaches to their cultivation. It will be useful to researchers, teachers and students in the fields of plant sciences, agriculture and forestry.

Contact: Springer Customer Service Centre, Haberstrasse 7, D-69126 Heidelberg, Germany. Tel: +49 (6221) 345 4301; Fax: +49 (6221) 345 4229; E-mail: orders-HD-individuals@springer. com.

Proteome Bioinformatics (Methods in Molecular Biology)

In Proteome Bioinformatics, expert researchers provide a mix of review and methodology chapters, which address the fundamentals of analysis methods, algorithms, data standards and databases. Chapters include practical considerations for analysing database search results, annotating genomes, speeding up searches, and responding to specific data processing challenges. As a volume of the successful Methods in Molecular Biology series, this work provides the kind of detailed description and implementation advice that is crucial for getting optimal results. It is an essential guide for the novice and expert alike.

Contact: The Humana Press Inc., 999 Riverview Drive, Suite 208, Totowa, New Jersey, United States of America. Tel: +1 (973) 256 1699; Fax: +1 (973) 256 8341; E-mail: humana@humanapr. com; Website:


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