VATIS Update Biotechnology . Sep-Oct 2007

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Biotechnology Sep-Oct 2008

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 biotech industry releases policy on biofuels

EuropaBio, the European association for biological industries, has released a consensus response to the integrated energy and climate change package proposal, endorsed by the Heads of State of the European Union earlier this year. The associations response contains a policy for first and second generation biofuels. The available biomass in Europe will need to increase in order to attain ambitious goals of biofuel use set by the European Union (5.75 per cent in 2010 and 10 per cent in 2020) in a sustainable and competitive way.

Cultivating energy crops on set-aside and non-cultivated land will contribute but not meet all the demand, according to EuropaBio.
The industry says that the output per hectare has to be increased. The quality needs to be improved using modern plant breeding techniques and biotechnology, in combination with state-of-the-art application of crop protection, to have crops with more fermentable carbohydrates or higher oil content. Another important step to increase the biofuel production is the development of second-generation biofuels. This involves the competitive production of biofuels from (hemi)cellulose and organic agricultural waste. Industrial biotechnology mainly (hemi)cellulose degrading enzymes with improved efficiency will be crucial to obtain this.
The EuropaBios recommendations specifically:
  • Calls upon the member states to implement, as soon as possible, the principle of binding targets for blending biofuels with petrol and diesel;
  • Supports a change in fuel standards to permit a higher biofuel content in blends of petrol and diesel; and
  • Advocates performance-based regulation that encourages efficient delivery of biofuels, which are most effective in reducing green house gas emissions.

To harvest the full potential of biofuels, EuropaBio encourages European legislators to follow a similar approach to the United States and China and initiate policy measures that will allow second generation biofuels to become a viable, commercial business within the following 4-6 years. This should include support to continued research in second-generation technologies and support for demonstration projects.


European Union considers approval for GMO products

European Union ministers and national experts are due to approve a genetically modified (GMO) sugar beet variety this month in spite of a long-running dispute over the use of biotechnology. Officials say around ten GMO products mostly maize types but also cotton, soybeans and a high-starch potato are scheduled for discussion at various levels of the European Union in the next few months.

Although the blocs member governments clash consistently over GMOs, never reaching the required majority under its weighted voting system to authorize new biotech products, that deadlock doesnt stop authorizations being granted. Since 2004, the European Commission, the European Unions executive arm, has approved around a dozen GMO products a move that brings it into line with European Union law when countries fail either to endorse or reject a draft GMO authorization after a certain time. The Commission has authorized a string of GMOs in this way, outraging green groups.

The first of this years applications for GMO crops that is certain to be approved is a sugar beet called H7-1, developed jointly by the biotech giant Monsanto and a German plant breeding company KWS SAAT AG. The variety has resistance to glyphosate-containing herbicides.


GM seeds banned in Western Australia

Genetically modified (GM) seeds will be prohibited for cultivation, sale or import in Western Australia under new laws introduced this week by the States Agriculture and Food Minister Mr. Kim Chance. The Seeds Amendment Bill 2007 is designed to further protect the States moratorium on the growing of GM crops.

Under the proposed changes, it will be an offence to import, sell or be in possession of prohibited seed in Western Australia for the purposes of cultivation, Mr. Chance said. This legislation is designed to protect Western Australias GM-free cropping systems from intentional or inadvertent GM contamination, he added. GM contamination had been previously detected in the States canola crop, despite a moratorium in all canola-growing states of Australia. The Department of Agriculture and Food now continues to test for contamination of seed lines and harvested canola as an ongoing activity.

Western Australias GM-free status is providing benefits to Western Australian farmers in terms of price premiums for food-grade, non-GM canola and continued market access to discerning markets in Europe, Japan, India and China, said Mr. Chance. The legislation would help protect and maintain this market advantage. The Minister said the risks to the States GM-free canola cropping and grain handling systems could be further increased if other States lifted their moratorium in 2008. Western Australia has a moratorium in place until 2009.


Brazil approves Monsantos insect-protected corn trait

Brazils National Biosafety Technical Committee (CTNBio) has approved Monsanto Companys MON 810 insect protection event, known in the United States as YieldGard Corn Borer, for future commercial use in corn in Brazil. The regulatory process in Brazil is a multi-step process, and while other steps are still required, the Committees decision brings the technology closer to Brazilian farmers.

CTNBio is managed by the Ministry of Science & Technology and is charged with making science-based, technical assessments of biotechnology crops including commercial conditions of use. The approval by CTNBio may be followed by a review from the countrys National Biosafety Council (CNBS) to examine social and economic factors. Following a favourable review by the CNBS, and approvals of the individual MON 810 events in specific hybrid varieties, farmers will be able to plant these higher-yielding seeds.


Serbia and Denmark to trial explosive-detecting GM Arabidopsis plants

Serbia and Denmark have given the green light to field trials of Arabidopsis plants that can be used to detect the presence of explosives and landmines in the soil. The deliberate release will take place in an area close to Novi Sad in Serbia, and will be conducted by Areasa, a Danish plant biotechnology company, in cooperation with the agricultural institute NS Seme in Novi Sad. Trials will also commence immediately in Jgerspris, Denmark.

The approval is an important milestone in Aresas further development of the landmine detection plant RedDetectTM. It is important to Aresa to be able to test the plants outside Denmark, and more importantly in an area where landmines do occur and soil conditions are similar to where we potentially are going to detect landmines and other explosives, said Mr. Ole Andersen of Aresa. The company plans to transfer the RedDetect technology to tobacco plants by next year, thereby increasing the robustness as well as the commercial potential of the technology.


Australian state passes stem cell laws

Queensland has become the third Australian state to pass laws allowing research involving embryonic stem cells, following Victoria and New South Wales. Queensland MPs reportedly voted 48 to 34 in a conscience vote, to allow stem cell research to go ahead under strict conditions.

Ms. Anna Bligh, Premier of Queensland said that embryonic stem cell research must be allowed, but under tight national restrictions, for Queensland to thrive as a smart state and potentially discover cures for certain diseases. Laws that ban cloning a human for reproductive purposes or placing a human embryo in an animal or vice-versa remain in place, and anyone breaching the restrictions faces up to 15 years in jail. Stem cell researchers would require a licence from the National Health and Medical Research Council to carry out their research.



ThromboGenics transfers thrombolytic agent technology to Bharat Biotech

ThromboGenics NV, Belgium, has announced the successful completion of technology transfer to Bharat Biotech International Limited, India, for the manufacture of THR-100, a novel variant of recombinant staphylokinase. THR-100 is a thrombolytic agent developed for the treatment of acute myocardial infarction (AMI) and other vascular diseases, based on its ability to dissolve blood clots.

ThromboGenics had earlier announced the completion of a licence agreement with Bharat Biotech to manufacture, develop and commercialize THR-100 as a replacement for established thrombolytics, such as streptokinase and urokinase, in developing countries.

Bharat Biotech will use its manufacturing capabilities, and the technological expertise acquired from ThromboGenics, to produce clinical-grade material for upcoming clinical trials. THR-100 has completed Phase II clinical trials in Europe for treatment of AMI, and is expected to enter Phase III in India later this year.


Immunotherapeutics to invest in R&D and production

Immunotherapeutics Ltd., India, a 100 per cent subsidiary of American Bio Sources (ABS) Inc., the United States, has earmarked an investment of Rs 1 billion (about US$25 million) to establish R&D and manufacturing facilities. The locations are being identified at Hyderabad and Bangalore. The investments will be sourced through public funding.

The company will manufacture novel vaccines for prevention of infections, monoclonal antibodies (MABs), cancer therapeutics and cardio-vascular bio-pharmaceuticals, said Dr. Niranjan Kumar, Chairman and Managing Director. The company will receive technology from its parent company and also offer its facility for contract manufacturing services, stated Dr. Kumar. We will also look at alternate locations like Pune for an R&D laboratory and New Delhi for manufacturing plant as part of our nation wide activities, he added. Immunotherapeutics is ready for clinical trials in India for the novel bacterial and viral vaccines, which are already launched globally. The company will go in for production in 2008-end and products will be available in India by mid-2009.


Acambis wins FDA approval for new smallpox vaccine

Acambis plc, the United Kingdom, has received approval from the United States Food and Drug Authority for its smallpox vaccine ACAM 2000, the first new bio-defence vaccine to be licensed since the United States government launched Project Bioshield in 2001. The company previously supplied 192.5 million doses of the vaccine under the investigational new drug application, and the licence paves the way for it to agree to a deal with the Centres for Disease Control and Prevention (CDCs) for a warm base manufacturing contract to maintain the stockpile. The warm base contract will require Acambis to keep its United States facility in readiness to manufacture ACAM 2000.

Military personnel are required to be vaccinated if they are posted to threat areas, and it is planned to switch from the current Dryvax vaccine manufactured by Wyeth, the United States, to ACAM 2000 now that it is licensed. Those doses will be supplied from the CDCs stockpile. ACAM 2000 has an equivalent safety and efficacy profile to Dryvax, but is manufactured in cell culture using animal-free serum.

More than 3,800 subjects were vaccinated in two Phase III studies of ACAM 2000. One demonstrated non-inferiority to Dryvax in producing a scab at the injection site in people not previously vaccinated against smallpox a generally accepted surrogate endpoint. There was a 96 per cent response in the ACAM 2000 group compared with 99 per cent in the Dryvax group. The second study demonstrated non-inferiority to Dryvax in generating an immune response in subjects previously exposed to the older vaccine. According to Acambis, apart from the United States, ACAM 2000 has been sold to 14 other governments.


Affymetrix and Empire Genomics enter into licensing agreement

In the United States, Empire Genomics LLC has obtained a non-exclusive, worldwide licence to a number of Affymetrix patents covering the manufacture, use and sale of nucleic acid microarrays and related products and services for comparative genomic hybridization. The arrays and services may be used for research or diagnostics. This agreement with Affymetrix enables Empire Genomics to bring its innovative genomics platform to market while continuing the advancement of personalized medicine. We fully expect that focusing in the field of copy number variation will lead to the discovery of the genomic causes of multiple diseases, as well as advanced therapeutic treatment strategies, said Empire Genomics CEO Mr. Anthony Johnson.


Dow AgroSciences and Hexima collaborate on cotton seed

Dow AgroSciences, based in the United States, has announced an agreement with Australias Hexima Ltd. to test cotton plants using Dows proprietary genetic constructs. The agreement involves the completion of a series of research activities, and testing over the next 18-24 months, resulting in the production of viable transgenic cotton seeds to provide better solutions and more options for cotton growers. This collaboration represents Dow AgroSciences commitment to provide differentiated solutions to customers globally through unique technology and capabilities, said Mr. Daniel R. Kittle, Dow AgroSciences Vice President for R&D.


Dako enters new collaboration on targeted NSCLC therapies

Dako of Denmark has entered into collaboration with Genentech, OSI and Roche for the clinical development and application for a pre-market approval supplement and CE marking of EGFR pharmDxTM for its use as a potential test in the assessment of patients of non-small cell lung cancer (NSCLC) considered for treatment with Tarceva (erlotinib).

Dako possesses substantial technical knowledge regarding the utility of immunochemistry for use in characterization of EGFR protein expression in tumour cells and markets EGFR pharmDx to assess clinical colon cancer tissue specimens for the presence of the EGFR protein, thereby assisting the physician in choosing appropriate therapy. Genentech, OSI and Roche have access to substantial proprietary and confidential technical and scientific information regarding their product Tarceva and were seeking a capable diagnostic collaborator.


Baxter signs flu vaccine deal

Baxter International, based in the United States, has entered into an agreement to supply the United Kingdom with flu vaccine in the event of a bird flu pandemic. The company is in the final stages of testing for a vaccine against H5N1 strains of avian influenza. Baxter will manufacture its pandemic vaccine in a serum-free, vero cell-based system that accelerates vaccine availability. The vaccines produced using this process can be released within approximately 12 weeks, significantly earlier than with traditional egg-based systems, the company said. The vero cell culture gives Baxter the flexibility to quickly respond to emerging variant pandemic virus strains.


Dyax Corp. collaborate with Bayer Schering Pharma for therapeutic antibodies

Dyax Corp., the United States, has entered into an agreement with Bayer Schering Pharma AG, based in Germany, for the discovery of therapeutic antibodies. Under the terms of this agreement, Dyax will identify therapeutic antibodies for two targets provided by Bayer Schering Pharma. Furthermore, these research activities may be expanded to allow Dyax to work on additional targets and/or allow Bayer Schering Pharma to exercise an option for an antibody library licence.

Dyax will receive clinical milestone payments and royalties on net sales that may result from Bayer Schering Pharmas development and commercialization of any antibodies discovered through the collaboration. The agreement also provides Bayer Schering Pharma with sub-licences to relevant third-party antibody phage display patents that may be used with Dyaxs technology.


Ablynx and Boehringer Ingelheim in global strategic alliance for nano-therapeutics

Ablynx, Belgium, and Boehringer Ingelheim, Germany, have announced a major global strategic alliance to discover, develop and commercialize up to ten different Nanobody therapeutics. Ablynx expects to receive 75 million during the research term of the collaboration, which includes 15 million proposed equity investment by Boehringer Ingelheim in Ablynx. Besides, Ablynx will receive development milestone of up to 125 million as well as undisclosed royalties payments for each Nanobody developed.

Ablynx and Boehringer Ingelheim will collaborate in the discovery of Nanobodies against agreed targets across multiple therapeutic areas including immunology, oncology and respiratory. Both parties will propose target opportunities for the collaboration with the goal of bringing Nanobody-based products rapidly to patients in need. The German company will be exclusively responsible for the development, manufacture and commercialization of any products that result from the collaboration. Ablynx will have some co-promotion rights in Europe.


ITC takes over Australian agri-biotech company

Diversified major ITC Ltd., India, has taken over the Australian agri-biotech company Technico Pty. Ltd. for an undisclosed sum, as part of a strategy to strengthen its foods business. The deal was executed through its subsidiary Russell Credit. An ITC spokesperson said the acquisition of Technico will help improve the profile of the companys foods business.

Technico is an agri-biotech company with operations in Canada, China, India and Middle East through its subsidiaries. It provides bulk potato supply chain management, and has the award winning Technituber seed technology, which it claims would revolutionize the global seed potato industry. The potato company provides supply chain solutions to global customers by using proprietary technology and a technology platform to implement affordable early field generation seed potato programmes, reduce seed exposure to soil-borne pathogens and rapidly introduce new varieties.


Generex Biotech to collaborate with Rochester University on avian influenza vaccine

Antigen Express Inc., the wholly-owned immunotherapy subsidiary of Generex Biotechnology Corp., the United States, has entered into an agreement with the University of Rochester as part of its efforts to develop a novel vaccine against the potentially pandemic avian influenza. The collaboration brings together Prof. John Treanor, at the Department of Medicine at the University of Rochester Medical Centre, and the novel peptide vaccine technology pioneered by Antigen Express.

Antigen Express is involved in the clinical development of peptides designed to potently stimulate CD4+ T helper cells through enhanced interaction with MHC class II molecules. Earlier this year, the Company began Phase I clinical studies of proprietary peptides derived from the hemagglutinin protein of the H5N1 avian influenza virus in healthy volunteers. Modified peptide vaccines for avian influenza can be manufactured by a fully synthetic process at lower cost but higher speed and quantity of production relative to traditional vaccines. Furthermore, the peptides are derived from regions of the virus that are similar enough in all H5N1 virus strains such that they would not have to be newly designed for the specific strain to emerge in a pandemic.



Reverse genetics for herbicide-resistance detection

A new molecular tool developed by Australian and Japanese researchers is expected to help farmers address what has become one of the major threats to conventional agricultural practices herbicide resistance. New South Wales Department of Primary Industries molecular biologist, Dr. Mui-Keng Tan, and a team of researchers led by Dr. Guang-Xi Wang from Kyoto University, Japan, investigated eco-tilling technique and found that it offers a quick, cheap and reliable means of detecting early signs of herbicide resistance in weeds.

Unlike the traditional molecular approach, eco-tilling uses reverse genetics. Genes are not fully sequenced; instead, mutations in single molecules that make up genes are identified purely on the basis of their position in the genome. Dr. Tan said new mutations can be detected and known ones can be screened for a fraction of the cost of alternative genetic methods. This makes it a powerful, low-cost and high-throughput alternative to full sequencing.

Dr. Tans research focused on herbicide resistance in two of the most significant weeds affecting Australian cropping systems wild oats and rye grass and to together with Dr. Wang she also examined weeds in rice fields in Japan. She said that every weed-herbicide system is specific, and the eco-tilling technique can be applied on any particular system.


Grapevine genome decoded

A group of researchers from France and Italy have deciphered the complete genome sequence for the pinot noir grapevine Vitis vitifera. The draft sequence of the grapevine genome is the first one produced for a fruit crop and fourth for a flowering plant after rice, Arabidopsis and poplar.

The French-Italian Public Consortium for Grapevine Genome Characterization, which collectively conducted the study, discovered a large number of gene families related to wine characteristics, like those coding for terpenes and tannins, compounds responsible for the wines aroma and taste. Multiple copies of the genes coding for enzymes necessary for the biosynthesis of resveratrol were also found. Resveratrol is an antioxidant found in red wine and known for its anticancer, antiviral, anti-inflammatory and neuroprotective properties. The large number of gene families was attributed to mans selection and hybridization during thousands of years. The findings will pave the way for genetic manipulations to improve the flavour and pathogen resistance of a crop that generates some US$200 billion a year in revenue. 


Estrogen can switch on breast cancer gene

A team of researchers from Australia has found that the female sex hormone estrogen can turn on a gene linked to breast cancer. The cancer biology team from the University of Queenslands Diamantina Institute for Cancer, Immunology and Metabolic Medicine in Brisbane says the finding helps explain the link between breast cancer, the gene known as MYB, and high levels of estrogen. What is important in breast cancer is the ability of estrogen to turn on MYB rather than there being a mutation in the gene itself, said the research team leader Dr. Tom Gonda. The gene MYB is found in about 70 per cent of all breast cancers and is one of several dozen genes called oncogenes that promote cancer growth. Researchers in Melbourne, Adelaide, and the United States worked with the University of Queensland team.


New complexity found in human genome

Geneticists from University of Toronto, Canada, have found that the human nervous system plays an important role in regulating genetic activity. Led by Professor Benjamin Blencowe, they were searching for mechanisms that could account for the genetic differences between simple and more complex life forms.

The researchers found that increased functional and cellular complexity can be largely explained by how genes and gene products are regulated. The researchers found a step in gene expression alternative splicing is more highly regulated in a cell and tissue-specific manner than previously thought and much of that additional regulation occurs in the nervous system. The step allows a single gene to specify multiple protein products by processing the RNA transcripts made from genes that are translated to make protein.


Scientists discover tall gene

Dr. Timothy Frayling and colleagues at Peninsula Medical School in Exeter, the United Kingdom, have discovered the first genetic link to height. Their study shows that a single letter change in the DNA sequence of a gene called HMGA2 can boost a persons height by around 1 cm. Although height is thought to be 90 per cent down to genetics, scientists have previously had difficulty in identifying the hundreds of genes thought to be involved, in the absence of new technology that allows the entire genome of thousands of people to be analysed.

In the hunt for the gene, the researchers began by scanning the entire genome of 5,000 people to identify single letter changes linked to height differences. This led to the discovery of a tiny variation in the HMGA2 gene. Next, they looked for the same variation in another 29,000 people, confirming that the gene variant is linked to height. The researchers found that people who carry two copies of the tall version of the gene are an average of 1 cm taller than people who carry two copies of the short version, while those who carry one of each are somewhere in the middle.


Genetics of loneliness

People who experience chronically high levels of loneliness show gene-expression patterns that differ markedly from those of people who dont feel lonely, according to a new molecular analysis led by Dr. Steven Cole at University of California Los Angeles (UCLA) School of Medicine in the United States. The findings suggest that feelings of social isolation are linked to alterations in immune system activity, which result in increased inflammatory signalling within the body. This is the first study to show an alteration in genome-wide transcriptional activity linked to a social epidemiological risk factor. It thus provides a genetic framework for understanding why social factors are linked to an increased risk of diseases where inflammation is thought to be a factor, such as heart disease, infection and cancer.

In their study, Dr. Cole and colleagues at UCLA and the University of Chicago used DNA microarrays to survey the activity of all known human genes in white blood cells from 14 individuals. Six participants scored in the top 15 per cent of the UCLA Loneliness Scale (a widely used measure of loneliness that was developed in the 1970s), the others scored in the bottom 15 per cent. The researchers found 209 transcripts were differentially expressed between the two groups, with 78 being overexpressed and 131 underexpressed.

Genes overexpressed in highly lonely individuals included many involved in immune system activation and inflammation. However, several key gene sets were underexpressed, including those involved in antiviral responses and antibody production. Bioinformatics analyses identified some of the biological signalling pathways that shaped these differences in gene expression, including reduced activity of the anti-inflammatory glucocorticoid pathway and the pro-inflammatory NF- B/Rel pathway. The changes in immune cell gene expression were specifically linked to the subjective experience of social distance. The changes were even independent of the objective size of a persons social network. What counts, at the level of gene expression, is not how many people you know; it is how many you feel really close to over time, he added.


The genes involved in rheumatoid arthritis identified

The results from screening of the human genome for the genetic causes of rheumatoid arthritis both confirm previous hypotheses and turn the spotlight on entirely new genes. An international team of researchers from Sweden, the United States and Singapore led by Prof. Lars Klareskog and Prof. Lars Alfredsson at the Swedish Medical University Karolinska Institutet compared the genomes of over 15,000 rheumatics with those of 1,850 controls. Their analysis shows that the DNA of these two groups are at a variance at three sites, two genes previously linked to the disease and a previously unexamined gene complex known as TRAF-C5.

The scientists have also used the same material to examine the significance of a specific area of the genome. They found that yet another gene, STAT 4, could be linked to the disease. The previously studied genes and the newly discovered TRAF-C5 and STAT4 genes are each important in its own way for the function of the bodys immune cells.


Gene for glaucoma found

A group of scientists has discovered two common single nucleotide polymorphisms (SNPs) in the sequence of the human genome that appear to account for 99 per cent of cases of exfoliative glaucoma (XFG). The scientists from deCODE Genetics and the National University Hospital in Rekjavik, both in Iceland, and from the Uppsala University in Sweden reported that the SNPs are located in the lysyl oxidase-like 1 gene (LOX1) on Chromosome 15. This finding offers hope for more efficient diagnosis and treatment of XFG.

The team began its work with an analysis of over 300,000 SNPs using DNA scanning chips. By comparing patients and control subjects, the scientists were able to determine the sites linked with the disease. Dr. Kari Stefansson, CEO of deCODE, and his colleagues discovered two risk variants in the LOX1 gene that are strongly linked to XFG; these SNPs confer increased risk of 26-fold and 8-fold compared with the low-risk versions of the same markers. Over 16,000 patients and controls took part in the study.

The LOX1 protein encoded by the gene is produced in many tissues of the body, including the eye, and is involved in cross-linking elastin fibres. The effect of the genetic variants seems to be to lower the production rate of this protein. In XFG, microfibullar deposits build on the surfaces on the front of the eye, increasing fluid pressure that gradually damages the optic nerve, leading to a progressive loss of vision. According to Dr. Stefansson, the risk conferred by these variants is such that it accounts for virtually all cases of XFG, meaning that if the impact of these variants could be neutralized the disease could be eliminated.



Possible Hepatitis C vaccine

Hepatitis C virus infects 180 million people worldwide. Infection with the virus can lead to liver cancer, and is the most common reason for liver transplantation in countries like the United Kingdom and the United States. In a collaborative effort with groups across Europe and the United States, scientists from Nottingham University, the United Kingdom, have identified antibodies that can prevent infection with many diverse strains of Hepatitis C virus in laboratory models.

The clinical potential of this work cannot be overstated. Historically, successful vaccines against viruses have required the production of antibodies, and this is likely to be the case for Hepatitis C virus, says Dr. Alexander Tarr from the Virus Research Group at the University of Nottingham. Identifying regions of the virus that are able to induce broadly reactive neutralizing antibodies is a significant milestone in HCV vaccine development. We are using the information gained by identifying and characterizing the antibody responses to Hepatitis C virus to design new ways of making vaccine candidates. If the antibodies we have discovered can be reproduced by vaccination, control of the disease might be possible says Dr. Tarr.


Cancer cell signalling pathways liked with proliferation of embryonic stem cells

In the United States, researchers from Novocell Inc., Invitrogen and the University of Washington collaborated to identify for the first time two prominent cancer cell signalling pathways as vital for the efficient proliferation and self-renewal of human embryonic stem cells (hESCs).

The researchers studying the self-renewal of hESCs discovered a link with insulin-like growth factor-1 (IGF-1R) and ERBB2/3. Both pathways are highly implicated in cancer and the targets of numerous oncology therapeutics. ERBB2 is often overexpressed in breast cancer and in other malignancies and is the target of the monoclonal antibody Herceptin.

These new findings indicate for the first time that the major signalling pathways driving the self-renewal of human embryonic stem cells are also key pathways that signal inappropriately in a number of different cancers, said Dr. Allan Robins, Vice President and Chief Technical Officer of Novocell. Such a linkage provides an avenue for potential identification of new targets for oncology therapeutics using hESCs.


HIV drug shows cancer promise

Dr. Phillip Dennis and colleagues at the National Cancer Institute, the United States, have begun testing HIV drugs on cancer cells after noticing that the toxic effects the virus has on cells are similar to the changes seen in cancerous cells. Three of the drugs significantly slowed the growth of the tumour cells and increased cell death, the researchers reported. Nelfinavir proved the most effective of the three drugs, impeding the activity of protein-degrading enzymes in the cell and blocking tumour growth in mice injected with cancer cells. Cancer scientists said repositioning drugs approved as HIV therapies could help save lives by reducing the wait and cost of getting a cancer drug from the laboratory to the patient.


Scientists identify stem cells in tendons

In the United States, scientists have discovered stem cells in adult tendons can regenerate tissue, a finding that promises new treatments for tendon injury and disease. Led by Dr. Yan-ming Bi of the National Institutes of Health, the scientists identified unique cells within the adult tendon that have stem-cell characteristics, including the ability to proliferate and self-renew. They were able to isolate the cells and regenerate tendon-like tissue in an animal model. Clinically, tendon injury is a difficult one to treat, not only for athletes, but for patients who suffer from tendinopathy, such as tendon rupture or ectopic ossification, said Dr. Songtao Shi from the University of Southern California School of Dentistry. We now know how to collect them from tissue and how to control their formation into tendon cells.


Research points to new stroke therapy

New research from an international team of scientists has identified a possible new therapy for stroke that is expected to be more effective than current treatments. The team found that administering immunoglobulin (Ig) directly into the veins via intravenous injection protected brain cells from the effects of stroke. Ig is a class of protein produced by the blood to fight off foreign substances in the body.

Prof. David Fairlie from the Institute for Molecular Bioscience at the University of Queensland, Australia, explained that a stroke reduced the flow of oxygenated blood to the brain, causing tissue death. But intravenous immunoglobulin treatment reduced the amount of dead tissue in the brain by 50 to 60 per cent. This finding seriously raises the prospect of using intravenous immunoglobulin treatment as an interventional therapy for stroke, he added.

Current management of stroke consists mainly of prevention and reducing the risk factors associated with stroke, such as high blood pressure, thrombosis and thickening of the main artery that supplies blood to the brain. Once someone has actually had a stroke, therapy is limited to administering an enzyme designed to break down blood clots, Prof. Fairlie said. However, this enzyme must be given to the patient within three hours of the stroke; otherwise, it increases the risk of excessive bleeding, leading to another stroke, he said. Intravenous Ig treatment does not have this side-effect. The team has suggested clinical trials be considered to further evaluate the use of the treatment in stroke patients.


More light on malarial parasite

Indian researchers have moved a step further in the fight against malaria by getting a deeper insight on the malarial parasite, belonging to the genus Plasmodium. In a new study, the researchers from the Indian Institute of Science constructed a chaperone interaction network for the parasite which provides, for the first time, a logical basis for the anti-malarial effect of known drugs and highlights new proteins that could be employed.

Recent reports from several labs point to a crucial role played by a group of proteins termed molecular chaperones. These chaperones participate in the maintenance and growth of cells and are implicated in parasite survival and growth. Despite the vast body of information available regarding individual chaperones, few studies have tried a systems level analysis of chaperone function.

The systems-level approach of Dr. Utpal Tatu and colleagues provides information on 95 different chaperones in the parasite and also gives insights into their business partners and cellular processes that they might regulate. Analysis of the network reveals the broad range of functions regulated by chaperones. The network predicts involvement of chaperones in chromatin remodelling, protein trafficking and cytoadherence. More importantly, it allows making predictions about the functions of hypothetical proteins based on their interactions.


Orphan drug designation for ALS-357 in metastatic melanoma treatment

Advanced Life Sciences Holdings Inc. (ALSH) announced that the United States Food and Drug Administration (FDA) has granted orphan drug designation to its oncology product, ALS-357, for the topical treatment of metastatic melanoma. ALS-357 is a novel drug entering phase I/II clinical development that has demonstrated potent anti-tumour activity against malignant melanoma. It has shown promise in both in vitro and in vivo pre-clinical studies. Rapid tumour regression has been shown in a mouse model and no toxicity was seen even at high doses. ALS-357 operates by inducing apoptosis, or programmed cell death, in the tumour cells.



New biomarker for peripheral artery disease

A protein biomarker known as beta-2 microglobulin may assist physicians in identifying patients with peripheral artery disease (PAD), according to research led by scientists at Stanford University, the United States. The researchers analysed plasma samples from 45 patients with PAD and 43 patients with risk factors for PAD, but without the disease itself, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to quantify a total of 1,619 protein peaks. The study confirmed that the peak intensity of beta-2 microglobulin was higher among patients with PAD than among those without PAD.

Another study revealed higher levels of the biomarker in the plasma of patients with PAD than in that of patients with coronary artery disease and no PAD. Plasma beta-2 microglobulin level correlated with functional capacity and ankle brachial index, and was an independent predictor of PAD when combined with C-reactive protein level.
This biomarker discovery may provide new insight into the patho-physiology of PAD and may contribute toward the development of our panel of biomarkers to identify patients at risk for PAD, said Dr. Eric Fung, Chief Scientific Officer of Vermillion Inc., a diagnostics company that aims to work with the researchers to develop a blood test for PAD incorporating the new marker.


Blood protein linked to pancreatic cancer

A study led by Dr. Brian M. Wolpin at the Dana-Farber Cancer Institute in Boston, the United States, points to possible link between the blood protein related to body weight and physical exercise levels and pancreatic cancer risk. It supports the link between obesity and a sedentary lifestyle with an increased risk of pancreatic cancer, with a high mortality rate but difficult to catch early. This grim prognosis has prompted scientists to identify the risk factors for pancreatic cancer.

The investigators looked at whether blood levels of a protein known as insulin-like growth factor binding protein-1 (IGFBP-1) were related to the risk of developing the cancer. IGFBP-1 inhibits the activity of insulin-like growth factor-1 (IGF-1), a hormone that can assist the growth and spread of cancerous pancreatic cells. The researchers measured levels of IGFBP-1 in 573 subjects enrolled in several large, ongoing clinical trials. Four years later, 144 had developed pancreatic cancer. The men and women with the lowest levels of IGFBP-1 were twice as likely as those with higher levels to develop pancreatic cancer. Low IGFBP-1 levels are typically found in obese and inactive individuals.

Several studies have shown that obesity and lack of exercise may raise the risk of pancreatic cancer, with the evidence being stronger for obesity. The current findings therefore indirectly support them as risk factors for pancreatic cancer, said Dr. Wolpin. More importantly, the study points to a reason for the connection. Since IGFBP-1 binds to and sequesters IGF-1, Dr. Wolpin explained, people with chronically low IGFBP-1 levels would have more free IGF-1 in the circulation, interacting with body cells. In theory, IGF-1 would be better able to promote the growth of pancreatic cancer cells.


New mechanism discovered for DNA recombination and repair

A Taiwanese biochemistry research team led by Dr. Andrew H.-J. Wang and Dr. Ting-Fang Wang at the Institute of Biological Chemistry, Academia Sinica (IBCAS), has discovered that the RecA family recombinases function as a new type of rotary motor proteins to repair DNA damages. Homologous recombination (HR) is a mechanism that repairs damaged DNA with perfect accuracy, and it utilizes the homologous sequence from a partner DNA as a template. This process involves the bringing together of two DNA molecules, a search for homologous sequences and exchange of DNA strands.
RecA family proteins are the central recombinases for HR. The family includes prokaryotic RecA, archaeal RadA and eukaryotic Rad51, and Dmc1. They have important roles in cell proliferation, genome maintenance and genetic diversity, particularly in higher eukaryotes.

Since the discovery of RecA proteins, it has been assumed that RecA (and other homologues) forms only 61 right-handed filaments (six protein monomers per helical turn), and then hydrolyses adenosine triphosphate (ATP) to promote recombinational and HR DNA repair. How the energy of ATP facilitates DNA rotation during the strand exchange reaction was a puzzle.

The IBCAS scientists have reported that archaeal sulfolobus solfataricus RadA proteins can also self-polymerize into a 31 right-handed filament with three monomers per helical turn and a 43 right-handed helical filament with four monomers per helical turn. Further analyses revealed that RecA family proteins may couple ATP binding and hydrolysis to the DNA strand exchange reaction in a manner that promotes clockwise axial rotation of nucleoprotein filaments.

Specially, the 61 RadA helical filament undergoes clockwise axial rotation in two discrete 120 steps to the 31 extended right-handed filament and then to the 43 left-handed filament. As a result, all the DNA-binding motifs (L1, L2 and HhH) in the RadA proteins move concurrently to mediate DNA binding, homology pairing and strand exchange, respectively. Therefore, the energy of ATP is used to rotate not only DNA substrates but also the RecA protein filaments.


New prion protein discovery may shed light on mad cow disease

Scientists have discovered a new protein that may offer fresh insights into brain function in mad cow disease. The study was conducted jointly by the Canadas University of Toronto and University of Alberta, and Case Western Reserve University and McLaughlin Research Institute in the United States. Our team has defined a second prion protein called Shadoo that exists in addition to the well-known prion protein called PrP, said Prof. David Westaway, Director of the Centre for Prions and Protein Folding Diseases at the University of Alberta.

The discovery challenges the long-held view that PrP is a unique nerve protein that folds into an abnormal shape and causes mad cow disease. This is the first discovery since 1985 of a new brain prion protein, though a second prion protein had been earlier inferred by other studies and the examination of DNA sequences.

The study has also defined an unexpected alteration in prion infections, says lead author Mr. Joel Watts, a graduate student at the University of Torontos Centre for Research in Neurodegenerative Diseases. As the PrP molecule alters shape and accumulates in a prion-affected brain, the Shadoo protein seems to disappear, he said. Since proteins in a living cell are the molecules that do the work, this is likely to be significant, Mr. Watts added.


Second protein that doubles muscle-building effect

In the United States, Dr. Se-Jin Lee, the Johns Hopkins scientist who first showed that the absence of the protein myostatin leads to oversized muscles, has now found a second protein whose overproduction in mice lacking myostatin doubles the muscle-building effect. Results of Dr. Lees new study show that while mice which lack the gene that makes myostatin have roughly twice the amount of body muscle as normal, mice without myostatin that also overproduce follistatin, the second protein, have about four times as much muscle as normal mice. This muscle increase could significantly boost research efforts to beef up livestock or promote muscle growth in patients with muscle wasting diseases.

Dr. Lee first discovered that follistatin was capable of blocking myostatin activity in muscle cells grown under lab conditions. When he gave it to normal mice, the rodents bulked up, just as would happen if the myostatin gene in these animals was turned off. He then genetically engineered a mouse that both lacked myostatin and made extra follistatin. If follistatin were to increase muscle growth solely by blocking myostatin, then follistatin would have no added effect in the absence of myostatin. Dr. Lee found an additive effect, and noted that these muscular mice averaged a 117 per cent increase in muscle fibre size and a 73 per cent increase in total muscle fibres compared with normal mice. This is significant, as most agents targeting this pathway, including drugs i use, block only myostatin and not other related proteins.



Scientists uncover plants vitamin C secret

Agricultural scientists have uncovered the last big secret of vitamin C in plants. The breakthrough in understanding just how plants manufacture vitamin C will enable Hortresearch, New Zealand, to identify DNA markers for individual plants that naturally produce high levels of the vitamin. These plants are likely to be used in selective breeding programmes to produce fruits with more vitamin C in a form easily retained by the body, unlike large doses taken in vitamin pills.

Hortresearchs General Manager (Science), Dr. Bruce Campbell, said his team has isolated the last undiscovered enzyme and proved that it controlled vitamin C in plants. The scientists studied kiwifruit, a plant naturally high in vitamin C, with typical green kiwifruit bred from Actinidia deliciosa containing about 100 mg in each 100 g of fruit. They also worked on an inedible wild kiwifruit variety called Actinidia eriantha with a white, hairy skin, which is easy to peel because it contains a massive 800 mg of vitamin C per 100 g.


Sorghum may benefit from cloned toxicity-tolerant gene

When soils are too acidic, the aluminium that is locked up in clay minerals dissolves into the soil as toxic ions, making it hard for most plants to grow. Aluminium toxicity in acidic soils limits crop production in as much as half the worlds arable land, mostly in developing countries in Africa, Asia and South America. Now, researchers at Cornell University, the United States, have cloned a new aluminium-tolerant gene in sorghum and expect to have novel genetically engineered aluminium-tolerant sorghum lines by next year. Sorghum is an important food crop in Africa, Central America and South Asia and is the worlds fifth most important cereal crop.

Research by Dr. Leon Kochian a Cornell adjunct professor of plant biology and director of the Plant, Soil and Nutrition Laboratory of the United States Department of Agriculture Agriculture Research Service (USDA-ARS) and colleagues showed that in aluminium-tolerant sorghum varieties, special proteins in the root tip release citric acid into the soil in response to aluminium exposure. Citric acid binds aluminium ions very effectively, preventing the toxic metal from entering the roots.

The researchers used genetic mapping to identify a single gene that encodes a novel membrane-transporter protein responsible for the citric acid release. They discovered that the gene is only turned on to express the protein and transport citric acid when aluminium ions are present in the surrounding soil. The researchers have now used the sorghum gene to engineer aluminium-tolerant transgenic Arabidopsis thaliana and wheat plants. The map-based cloning of this agronomically important gene in sorghum is helping advance this species as a model for further exploring the aluminium tolerance mechanisms and discovering new molecular genetic solutions to improving crop yields, Dr. Kochian said.


Genetically modified eucalyptus as carbon sink

Eucalyptus trees genetically modified by a team of biologists from Taiwan and the United States have proven capable of ingesting up to three times more carbon dioxide (CO2) than normal strains, indicating a new path to reducing greenhouse gases and global warming. The scientists from the Taiwan Forestry Research Institute (TFRI) and North Carolina State University in the United States carried out the gene modification project that not only creates eucalyptus with a higher than normal CO2 absorptive capacity, but also causes them to produce less lignin and more cellulose.

TFRI researcher Dr. Chen Zenn-zong explained that cellulose, hemicellulose and lignin in trees are all created from carbon elements. However, only cellulose can be used in commercial processes of pulp manufacture and bio-ethanol extraction, he added. The project therefore aims to increase the value of genetically modified eucalyptus to related industries by adjusting the ratio of lignin and cellulose. Meanwhile, we enhance the trees capacity in absorbing CO2 to reduce greenhouse gases, so that more trees planted for production, the more CO2 are consumed, said Dr. Chen. With every eucalyptus carrying 18 per cent less lignin and 4.5 per cent more cellulose, he estimates that a pulp factory with an annual output of 1 million tonnes could generate extra revenue of about US$36 million every year.


Discovery promises more nutritious cassava

Scientists from the International Centre for Tropical Agriculture (CIAT), Colombia, have developed a new cassava variety that might be more nutritious and easier to digest than other varieties. Cassava is the staple food for millions of poverty stricken people in Sub-Saharan Africa, South America and parts of Asia. Cassava root is rich in carbohydrates and starch, but low in protein and vitamins. Compared with other starchy crops, cassava contains relatively higher levels of amylose, which render it difficult to digest.

Dr. Hernan Ceballos and his colleagues from CIAT identified a new cassava variety with significantly reduced amylose content. Compared with traditional hard-to-digest cassava varieties with 17-25 per cent amylose content, the mutant contains an average of only 3.4 per cent amylose. The scientists found no reduction in its starch content; therefore it can provide more carbohydrates compared with traditional varieties. This is the first report of a natural mutation in cassava that resulted in drastic reduction of amylose content in root starch. Besides being more nutritious and easily digestible, the new variety may also be better suited for bioethanol production.


GM potatoes with better freezing tolerance

Potato, the fourth most important food crop, is a frost-sensitive species incapable of cold acclimation. A brief exposure to frost can significantly reduce yield, while hard frosts can completely destroy entire crops. Improvement in its freezing tolerance by just a few degrees would thus be of considerable benefit. A group of researchers from Oregon State University and Michigan State University in the United States, and Kyung Hee University in Republic of Korea, has genetically altered potato to be more tolerant to freezing.

Although genetic donors, particularly the cold-acclimatized wild potatoes of South America, exist, transfer of freezing tolerance to cultivated plants proved to be unsuccessful because of the complex genetics of the trait and the introduction of undesirable agronomic properties. By introducing the AtBCF genes for freeze tolerance from Arabidopsis with an activation control (promoter) only for cold conditions, scientists successfully obtained several potato lines with increased freezing tolerance of up to -5C. They also found out that the attachment of the cold-inducible promoter minimize the expression of agronomically undesirable traits, like delayed flowering and retarded growth, previously attributed to the AtBCF genes.


New flood-tolerant rice variety

The Philippine Rice Research Institute (PhilRice) has developed a new rice variety tolerant to flood water and resistant to the bacterial blast, stemborer and tungro, three of the most dreaded rice pests.

The new variety, Tubigan 7, was developed using the DNA marker-assisted selection (MAS) technique. It is the first-ever successful DNA-MAS product developed in the Philippines, and the second locally developed biotech rice, after the tissue cultured variety of improved traditional Wagwag grains. Tubigan 7 has a fertility restorer trait and could yield about 8 tonnes per hectare during the dry season cropping and 5-6 tonnes per hectare during the wet season, and yields about 15 percent higher than the conventional harvest record in the Philippines.

Dr. Antonio A. Alfonso, head of plant breeding and biotechnology division of PhilRice, emphasized that Tubigan 7 is not a genetically modified crop, as the new variety was obtained through conventional breeding. The countrys National Seed Industry Council (NSIC) has officially released it as a variety.


New corn high in phytase

Chinese scientists have developed a genetically modified (GM) corn that could help improve the nutritional value of livestock feed and reduce pollution. The research work was carried out by the Chinese Academy of Agricultural Sciences (CAAS), and the corn has now entered pre-production field trials. The GM corn produces seeds containing high levels of the phytase enzyme, which helps livestock to digest phosphorus. Animals lack phytase in their system. As a result, farmers have to add the enzyme to animal feed to help livestock digest phosphorus.

The CAAS scientists isolated the gene that produces phytase from the fungus Aspergillus, and inserted it into corn. Initial tests have shown that the rate of seed germination, growth speed and yield of the GM corn are no different as compared with regular varieties. The scientists said that, under current industry criteria for feed additives, adding just a few grams of the GM corn seed per kilogram of animal feed would satisfy livestocks nutritional demand for phosphorus. If the technology is commercialized, Chinese farmers could save up to US$60 million per year in buying industrial phytase.


Marker-free GM Soybean produces by gene excision

Selectable marker genes are used in plant transformation systems to select transgenic events, but often the marker gene is no longer needed after the transgenic plants are regenerated. Their continued presence has always been the focus of criticisms in genetic improvement of crops. A group of researchers from DuPont recently produced transgenic soybean lines, which are free from marker genes and tolerant to glyphosate, through a self-activating gene excision system.

Unlike other approaches to produce marker-free plants, the gene excision system employed by the researchers delivers precise outcomes and does not require additional manipulations of the transformation and regeneration process. The glyphosate tolerance and marker genes were introduced along with a gene coding for the enzyme Cre recombinase, which will remove itself and the marker gene immediately upon induction. This self-activating gene excision strategy is currently being applied to numerous plants like maize, cotton and groundnut, and many coniferous trees.



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