VATIS Update Biotechnology . May-Jun 2006

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Biotechnology May-Jun 2007

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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Landmark decision reached on trade in GM products

A landmark agreement was reached in March 2006, with 132 countries agreeing to the rule on the international trade in products containing ge- netically modified (GM) organisms. The rule, made at the meeting of the Parties to the Cartagena Protocol on Biosafety, covers how such products are labelled. It states that any shipments containing GM organisms must state this, and identify which organisms are present, what their intended use is, and how they have been modified. If it is not possible to identify the GM organisms, shipments must bear a label saying that they may contain modified organisms. The countries that are party to the protocol will have four years to implement the rule.

According to Mr. Stavros Dimas, European Union Environment Commissioner, this decision sets out documentation requirements that are clear, meaningful and practical for both exporters and importers of agricultural products. It provides for legal certainty for international trade in agricultural commodities.


A milestone in the plant genetic resources treaty

The Islamic Republic of Iran has become the 100th country to ratify the International Treaty on Plant Genetic Resources for Food and Agriculture, the United Nations Food and Agriculture Organization (FAO) announced in May 2006. The treaty, which was approved by the FAO Conference in November 2001, entered into force on 29 June 2004, the 90th day after the deposit of the 40th instrument of ratification, acceptance, approval or accession in accordance with the provisions of the treaty.

The main objectives of the international treaty are the conservation and sustainable use of plant genetic resources for food and agriculture, and the fair and equitable sharing of the benefits that arise out of their use, in harmony with the Convention on Biological Diversity, for sustainable agriculture and food security. According to Mr. Clive Stannard of the Interim Secretariat for the Treaty, this record speed and level of ratification is an indication of the importance that countries attach to the objectives of the Treaty to ensure that plant genetic resources for food and agriculture, which are vital for human survival, are conserved and sustainably used and that benefits are equitably and fairly distributed. The implementation of the treaty would be discussed during the first session of the Governing Body of the International Treaty on Plant Genetic Resources for Food and Agriculture in Madrid, Spain, from 12 to 16 June 2006.


International study investigates early biology of HIV infection

An international virtual research centre the Centre for HIV/AIDS Vaccine Immunology (CHAVI) has been set up at Duke University, the United States. It has been awarded US$300 million over seven years to support efforts to develop an HIV vaccine. CHAVI investigators at institutions across the globe have agreed to share their expertise, technology, funding and findings.

The first of several research studies led by Dr. Myron S. Cohen at the University of North Carolina (UNC), the United States, is now under way and is aimed at gaining new knowledge into the biology of HIV infection during its earliest days, before the immune system produces antibodies to the virus. The UNC Centre for Infectious Diseases, which Dr. Cohen directs, has pioneered the development of techniques to recognize patients with the earliest phase of HIV. Dr. Cohen, leads the centres Study Site Core B, also known as the Acute HIV-1 Infections Network Core. CHAVI-001 is one of five study cores in support of the vaccine initiative. It is an observational study that will gather information at clinics in Africa (Malawi and South Africa) and in North Carolina, where patients statewide will be referred to UNC and Duke.

The initial goal of CHAVI-001 is to identify people with HIV still in its earliest stages, before sero-conversion. During the study, each individuals health will be tracked, and interviews aimed at identifying their sexual partners will try to determine the person who transmitted the disease, thus completing a transmission pair. According to Dr. Cohen, knowledge of the viral requirements for transmission is crucial to understanding how to make a vaccine against HIV. Knowledge of the immunological environment in which transmission occurred is also important to vaccine development, Dr. Cohen said. This means determining as close as possible to the time of transmission the kind of immune defences that can restrain viral replication.


Asian nations team up for bird flu research

Five Asian nations Cambodia, China, Indonesia, Thailand and Viet Nam and Canadas International Development Research Centre (IDRC) have launched a partnership to help identify ways of tackling outbreaks of bird flu. The Asian Research Partnership on Pandemic Influenza will study issues such as whether to vaccinate poultry in the wake of a bird flu outbreak. It will also support scientist exchanges, networking and information-sharing activities. IDRC has committed US$1.8 million and the five nations will also provide funds to the initiative. The partners include the Chinese Academy of Sciences, the National Research Council of Thailand, Viet Nams Ministry of Science and Technology, the Cambodian and Indonesian health ministries, and the Canadian Institutes for Health Research and the Public Health Agency of Canada. The partnership will also provide grants for research on the social and environmental impacts of bird flu.

According to Mr. Stephen McGurk, IDRC Regional Director for South-East and East Asia, the five Asian countries joining the partnership have quite different practices for controlling bird flu. Cambodia, China and Indonesia respond to outbreaks of the H5N1 bird flu virus by vaccinating poultry to protect them from infection. Thailand and Viet Nam have banned vaccination and they fear widespread vaccination could let the virus to continue spreading undetected or could help it become resistant to the vaccine.


Bhutan drafting national biosafety framework

The National Environment Commission (NEC) of Bhutan is preparing the National Biosafety Framework for the country. The trans-boundary movement of living modified organism or genetically modified products could have adverse effect on the conservation of biodiversity in the country. The need for Bhutan to have a National Biosafety Framework was felt, as it imports more than 35 per cent of its food products from the neighbouring countries.

According to NEC, public education on the framework was of utmost importance and having a National Biosafety Framework in place and the subsequent implementation of the framework must greatly enhance capacity and infrastructure needs of the government. The draft is expected to be ready by the end of June 2006 and will be submitted for the approval of the government.


Technology boost for millions of Chinese farmers

Chinas Ministry of Science & Technology (MOST) has entered into collaboration with the United Nations Development Programme (UNDP) under a US$8 million project, which would offer innovative and environmentally friendly technologies to Chinese farmers to increase their income and promote sustainable rural development. UNDP is investing US$1 million in the project and MOST is providing US$3 million, with the rest coming from local governments and smaller organizations.

The project will build on an existing MOST programme that sends technical task forces to the countryside to help farmers adopt relevant technologies, such as better irrigation techniques and seed varieties. So far, the Ministry has sent more than 20,000 technicians to rural communities in about 400 of Chinas 2,500 counties.

According to Mr. Khalid Malik, UNDPs China representative, UNDPs participation would bring advanced international management and experience and help spread the success of the project to other developing countries.


Bollgard cotton hybrids receive approval in India

The Genetic Engineering and Approval Committee (GEAC) of the Ministry of Environment & Forests, India, has granted regulatory clearance to 16 new Bollgard cotton hybrids in North and Central India. Farmers across these regions will now have access to a total of 36 Bollgard cotton hybrids in the 2006 planting season.

The companies that have received regulatory approval are Ganga Kaveri, Ajeet, Tulasi, Vikram, Vikki Agrotech, Emergent Genetics and Parvardhan this year along with the existing four seed companies. These companies are sub-licensees of Mahyco Monsanto Biotech (India) Ltd. (MMB) and have followed rigorous and large-scale field trials conducted in accordance with GEAC guidelines. MMB is a 50:50 JV between Mahyco and Monsanto Holdings and has co-licensing agreements with several Indian cotton seed companies to bring Bollgard to the Indian farmers. With this increase, the number of Bollgard hybrids available in the North and Central Zones has risen to 12 and 22, respectively.


Singapore unveils guidelines for GMO research

The Genetic Modification Advisory Committee under Singapores the Trade and Industry Ministry has released guidelines for research on genetically modified organisms (GMO). The guidelines were drawn up in consultation with the Health Ministry and the Agri-Food and Veterinary Authority. International guidelines and standards were also taken into account.

The guidelines will ensure that such experiments are properly regulated and supervised so that they will not pose a threat to public health. Currently, the researchers have to abide by the rules and regulations of their own institutes, but with the release of guidelines, they will now have a common framework to refer to. The overarching aim of the guidelines is to ensure that public safety is not compromised by the experiments.

Experiments on GMO will be divided under three categories: those considered to pose significant risks to the public or the environment, those dangerous to those directly involved and those that are safe. An independent Institute of Biosafety Committee will be set up to monitor them and researchers who flout the rules can be punished by current biosafety laws, although the guidelines will not be legislated.



Biotech industry close to net profit

According to Ernst & Youngs 2006 Global Biotechnology Report, in 2005, for the first time in its 30-year history, the biotechnology industry surpassed US$60 billion (49 billion) in revenues. This is an astounding growth considering that in 1996 industry revenues amounted to US$9.1 billion, which shows that thanks to strong sales, new products and mergers, the long-elusive goal of profitability for biotech firms is fast approaching.

In 2005, the global biotechnology industry cut its net loses by 30 per cent to US$4.3 billion, with the United States, Canada and the Asia-Pacific region collectively improving their bottom line by about US$3 billion. Publicly traded European biotech companies increased by 28 per cent, with strong growth in late-stage development. Mergers and acquisitions in Europe reached an all-time high of 66, as the sector emerged from a lengthy restructuring period. Also driving consolidation is the need for new products, since pharma had its biggest patent-expiration year ever in 2005, with an estimated US$23 billion worth of products losing protection, and recent safety-related product withdrawals have added to big pharmas pressures.

In the United States, the industry delivered strong product approvals and solid financial results, indicating signs of maturation: continued focus could therefore bring more product success, stable financial results and predictable valuations, the report finds. Furthermore, product success inevitably improved financial performance, as better product sales boosted sector revenues, which grew by about 16 per cent.

The best performance was seen in the Asia-Pacific region, however, with a scorching 46 per cent increase in revenues. In particular, Australias CSL boosted the countrys biotech revenues by over 60 per cent, allowing the Australian biotech sector to reach profitability ahead of the United States and Europe, and propelling Asian sector to break-even point as well. With Asian governments focusing on biotech as a strategic priority and foreign companies attracted to the region by growing drug markets, economic liberalization and stronger intellectual property protections, competition is fierce. Of particular interest is the specialization of many companies there into sectors such as contract research and manufacturing, vaccines, information technology and bioinformatics, traditional medicines and stem cells.


Oxford Genome Sciences and Medarex agree to collaborate

Oxford Genome Sciences Ltd. (OGeS), Oxon, the United Kingdom, and Medarex Inc., the United States, have entered into a strategic collaboration to discover and develop new human antibody therapeutics for the treatment of cancers, including colorectal cancer. The collaboration provides for OGeS and Medarex to discover, develop and commercialize therapeutic antibodies on a 50:50 basis.

The collaboration combines OGeS ability to discover novel targets for oncology with Medarexs expertise in the development of fully human antibody therapeutics. During the initial phase of the collaboration, OGeS intends to provide novel colorectal cancer targets, while Medarex expects to generate fully human monoclonal antibodies using its proprietary UltiMAb Human Antibody Development System. OGeS plans to utilize its unique Oxford Genome Anatomy Project database.


ABLE and BIOTECanada ink cooperation pact

A memorandum of understanding has been signed between the Association of Biotechnology Led-Enterprises (ABLE), India, and Canadas National Biotechnology Association (BIOTECanada) for closer cooperation in the biotech sector between the two countries.

The agreement forms the foundation of cooperation on issues of mutual interest that support the development of biotechnology in India and Canada. The industries in both countries are growing fast, with Canadian revenues reaching nearly US$4 billion last year a doubling in revenues in just five years. The biotechnology industry in India has just crossed a major threshold with over US$1.25 billion in revenue.

The collaboration is expected to help both nations to explore potential collaboration opportunities and developing technologies that will benefit the citizens in many different ways from improved healthcare treatments to healthier foods and a cleaner environment. The initiative by ABLE and BIOTECanada will impart the much-needed momentum in bringing together companies from both countries and in forging mutually beneficial relationships in the biotechnology sector.

Chronicle Pharmabiz, 4 May 2006

Delta and Pine Land to acquire Syngentas cotton seed assets

Delta and Pine Land Company (D&PL) a leading commercial breeder, producer and marketer of cotton planting seed has acquired Syngentas global cotton seed business, comprising operations and assets in India, Brazil and Europe, and certain cotton germplasm in the United States. Conventional and transgenic germplasm containing Syngentas VipCotTM insect-resistant cotton genes comprises the primary asset. D&PL had acquired a licence to VipCot in 2004 and expects to commercialize varieties containing these traits in 2008 or 2009, subject to receiving regulatory approvals.

According to Dr. Tom Jagodinski, President and CEO of D&PL, this acquisition further strengthens the companys already robust cotton germplasm portfolio and enhances their VipCot development pipeline. The acquisition of additional Indian assets is an excellent geographic fit and a natural extension of their business strategy. With this acquisition, they now have cotton seed germplasm and distribution assets in each of the three primary growing regions of India. According to Dr. Ioana Tudor, Syngentas Global Head for Corn, Soybean and Cotton Traits, Syngenta will continue to focus on the development of VipCot, a novel insect control trait.



PRA International acquires Synergy Systems

A memorandum of understanding to acquire the assets of the clinical research organization (CRO) Sterling Synergy Systems Private Limited, based in Mumbai, India, has been signed by a leading global CRO, PRA International of the United States. This is the first direct entry of PRA International to India to tap the potential in the field of clinical trial management in India. With more than 20 professionals as employees in its data management centre, Synergy has an extensive clinical trial site network and tie-up arrangements with leading hospitals in India, such as the Apollo Group, Tata Memorial, Kidwai Institute, Jaslok and Vellore CMC Hospital. Synergy is specialized in conducting cancer drug trial and data management.

PRA International had outsourced some of its international cancer drug trials to Synergy Systems earlier for conducting trials in India. Some of the clinical trials managed by Synergy include a phase III advanced renal cell carcinoma study on 214 patients in 12 centres, breast cancer drug trials in 200 patients at 18 locations, ovarian cancer drug trials, lung cancer trials, etc. More than 50 per cent of the trials conducted by PRA are also on in the field of oncology, and the acquisition would help the company to add to its strength. PRA has more than 2,500 employees worldwide and a track record of over 25 years.

Chronicle Pharmabiz, 18 May 2006

Rasi Seeds ties up with University of Ottowa

Rasi Seeds in Tamil Nadu, India, has entered into an MoU with the University of Ottawa, Canada, for import of gene. The company is awaiting clearance from the Review Committee on Genetic Manipulation (RCGM) for import of gene. Once the Committee clears the proposal, the company will import the material and commence to work on vegetables. The release of transgenic vegetables could, however, take another 3 or 4 years.

The company is in talks with the Tamil Nadu Agricultural University and Iltad Lab, the United States, on transgenic cassava. It is trying to work with the Central Tuber Crops Research Institute to explore the possibility of improving and developing disease-free cassava planting material. According to Rasi Seeds Managing Director Mr. M. Ramaswamy, the cassava crop suffered a huge setback in yield levels due to the mosaic virus. Both the area and yield are said to have dwindled considerably in the last couple of years from over 100,000 hectares (in Tamil Nadu alone) and yield potential of 35 t/ha to less than 15 t/ha at present.


Novartis gets US$220 million for influenza vaccine development

Novartis Vaccines has been awarded up to US$ 220 million by the United States Department of Health and Human Services (HHS) to support the development of a cell culture-derived influenza vaccine both to supply seasonal influenza vaccine and to respond rapidly in the event of an influenza pandemic.

Conventional vaccine production uses chicken eggs, which requires several months of logistics for ordering and receiving eggs. This lead-time can hinder the response to unanticipated demands such as the discovery of pandemic strains, production failures and seasonal influenza virus strain changes. Cell culture-derived influenza vaccines (commonly referred to as flu cell culture vaccines) use cell cultures for primary production. Flu cell culture production enables flexible, faster start-up of vaccine production, and is independent of the availability of eggs, providing an important advantage in the event of influenza pandemic.

The HHS contract commits up to US$220 million over five years to support product development, besides facility and equipment design and validation. Novartis plans to invest additional resources to ensure the successful establishment of a US-based vaccine manufacturing facility. At the time of reporting, discussions between Novartis and potential US site candidates were ongoing.



Scientists discover new gene responsible for spread of cancer

Scientists at the University of Liverpool, England, the United Kingdom, have identified a new gene that causes the spread of cancer. Professor Philip Rudlands group from the Universitys Cancer and Polio Research Fund Laboratories has discovered an additional member of the S100 family of protein genes, S100P, that causes the spread of cancerous cells from an original tumour to other parts of the body. If present in the primary tumour, metastagenes such as S100P trigger the rapid spread of cancerous secondary tumours to other tissues in the body via the bloodstream a process known as metastasis.

The new discovery builds on several years work carried out at the University to investigate the genes that cause cancerous tumours to travel to other tissues in the body. S100P is commonly found in ten different types of normal tissue including the placenta, spleen, colon, ovary, lung, prostate and heart. Scientists believe proteins like S100P function in healthy tissue by increasing the movement of white blood cells around the body. However, in a cancerous tumour, the protein causes the tumour to spread to other tissues.

According to Professor Rudland, it is the spread of cancer from the initial tumour that is the key contributor to death of a cancer patient. Metastagenes are fundamental to this process and can be found in most common cancers, including breast, lung and colon. If these genes are over-expressed in the cancerous tumour, early death of the patient is much more likely. The next major step is to develop drugs that will switch off the action of these genes. If this can be achieved, then the spread of the primary tumour could be stopped and the chances of survival for patients improved.


Study of the largest and last human chromosome published

The Wellcome Trust Sanger Institute and collaborating institutes in the United Kingdom and the United States have published the report of human chromosome 1 sequence the final chromosome analysis from the Human Genome Project. Chromosome 1 is home to more than 3,000 genes and more than 350 known diseases, including conditions as varied as Alzheimers and Parkinsons diseases, cancer development, high cholesterol and porphyria. The sequence has been used to identify more than 1,000 new genes and is expected to help researchers find novel diagnostics and treatments for many diseases. In the past year alone, genes involved in a dozen diseases, including cancer and neurological diseases, have been identified using the freely available chromosome 1 sequence.

The sequence of chromosome 1 is 223,569,564 bases of genetic code around 8 per cent of our genome and contains about twice as many genes as the average chromosome. About 4,500 single-letter changes in the genetic code (called single nucleotide polymorphisms or SNPs) were identified that could lead to changes in protein activity. In addition, 90 SNPs were found that would result in a shortened and possibly inactive protein. Although some 15 SNPs are associated with already known protection from malaria and predisposition to porphyria, the functions of these newly located SNPs are yet to be discovered.

The finished sequence of chromosome 1 enabled the team to collate chromosome-wide information associated with genetic variation from projects such as the HapMap a leading international study of human genetic variation. Our chromosome pairs recombine with each other, so that regions inherited from our two parents are shuffled when passed on to our children. Fine scale analyses have shown that recombination tends to be near to genes but outside the actual gene structures themselves. The team looked at correlations between the HapMap data and the annotated chromosome 1 sequence to investigate the variation between three human population groups with ancestry in Europe, Africa or Asia. Chromosome 1 is particularly susceptible to rearrangement and it is thought that disruption to genes within these rearrangements play a role in several cancers and in mental retardation. The high-quality sequence has already helped scientists around the world to home in on genes that affect a range of cancers.


Genome of influenza H5N1 viral isolates characterized

The complete genome of human influenza H5N1 viral isolates from Thailand has been characterized at Mahidol University, Bangkok. The complete genomes of three human H5N1 influenza isolates were characterized, together with the hemagglutinin (HA) and neuraminidase (NA) genes from two other human isolates and one chicken isolate. These six influenza isolates were obtained from four different provinces of Thailand during the avian influenza outbreak in Asia from late 2003 to May 2004. According to Dr. P. Puthavathana, who led the study, all six Thailand isolates contained multiple basic amino acids at the cleavage site in the RA gene. Amino acid residues at the receptor-binding site of the five human viruses were similar to those of the chicken virus and other H5N1 viruses from Hong Kong.

The presence of amantadine resistance in the Thailand viruses isolated during this outbreak was suggested by a fixed mutation in M2 and confirmed by a phenotypic assay. All genomic segments of the Thailand viruses clustered with the recently described genotype Z. These viruses contained more avian-specific residues than the 1997 Hong Kong H5N1 viruses, suggesting that the virus may have adapted to allow a more efficient spread in avian species.


A computer program for identifying disease genes

Scientists from ESAT-SCD (Engineering Sciences) and the Flanders Interuniversity Institute for Biotechnology, connected to the Catholic University of Leuven, have developed a computer program called ENDEAVOUR that compiles and process data from a variety of databases and identifies the genes that play a key role in the origin of a disorder. ENDEAVOUR, drawing on various databases, gathers all the data about genes that are known to be connected with a disease or a biological process and integrates these data into a mathematical model. This model shows the similarities between known genes and genes whose biological function is unknown, and whether the unknown genes could underlie a certain disorder.

The researchers took the data for a number of known genes from the mathematical model and then entered the genes as unknown into the program. For the majority of the syndromes tested (such as Alzheimers disease, leukaemia, colon cancer, and Parkinsons disease), ENDEAVOUR found the underlying genes and thus proved its validity. As an extra validation of the program, the researchers used it to look for new disease genes that underlie hereditary disorders. Among other things, they wanted to identify a new gene that can be correlated with DiGeorge syndrome, a genetic disorder that gives more than 1 in 4,000 newborn children deformed features and blood vessel abnormalities in the heart. ENDEAVOUR identified one gene as a possible disease gene: YPEL1. To biologically confirm this mathematical prediction, the researchers used the zebra fish that could not produce the YPEL1 gene. The embryos of these fish showed several abnormalities that are comparable to the symptoms of DiGeorge syndrome.


Genetic markers associated with early-onset heart attacks

Researchers from Celera Genomics, the University of California San Francisco (UCSF), Cleveland Clinic, Case Western Reserve University and Brigham Young University, have jointly discovered two novel genetic markers associated with an increased risk for myocardial infarction (MI) or heart attack. They evaluated DNA samples from more than 2,000 individuals in three studies to compare patterns of genetic variation in people with a history of early-onset MI and those with no history of MI, and identified two single nucleotide polymorphisms (SNPs) associated with increased risk for early-onset heart attack.

Novel genetic markers were identified in two genes, which had the same risk variants in all these studies: VAMP8 (involved in platelet aggregation) and HNRPUL1 (encodes a ribonuclear protein). These markers were identified through a genome-wide study covering 7,136 genes, focusing on SNPs that could influence gene function in order to increase the likelihood of identifying disease-causing gene variants. These were tested for association with early-onset MI in three case-control study studies with a total of 821 cases and 1,200 controls.



Researchers reveal apples protective ways

A team of scientists led by Dr. Eric Gershwin, professor of allergy, rheumatology and immunology at the UC Davis School of Medicine, the United States, has found that apple extract was able to protect cells from damage and death by interfering with communication between cells. Flavonoids which are found in chocolate and green tea, as well as fruits and vegetables behave as antioxidants, taking up free oxygen radicals that can damage precious DNA. The UC Davis study takes that knowledge further by looking beyond the antioxidant effects of apple flavonoids.

Dr. Gershwins team exposed human endothelial cells to an extract made from different apple varieties. The researchers then challenged these cells by exposing them to tumour necrosis factor (TNF), a compound that usually triggers cell death and promotes inflammation via a mechanism called the nuclear factor (NF) kappa B pathway. This pathway involves chemical signalling between cells. The apple extract was able to protect the cells from the normal lethal effects of TNF.

According to Dr. Gershwin, their study showed that the flavonoids in apples and apple juice can inhibit signals in this pathway that would otherwise damage or kill cells in the body. The method by which apple extract protects cells was different than that reported for other flavonoid-rich foods. Grape seed extracts, for example, do not affect the NF kappa B pathway. In addition, other studies indicated that it was not just the flavonoids in the apple extract that were important in protecting cells from genetic damage.


Novel candidate HIV vaccine vector

Researchers led by Dr. Dan H. Barouch at Beth Israel Deaconess Medical Centre (BIDMC), the United States, have created in collaboration with Crucell Holland BV, a Dutch biotechnology firm, a novel HIV vaccine strategy that overcomes the problem of pre-existing anti-vector immunity, which may prove a limitation of current lead AIDS vaccine candidates.

Lead AIDS vaccine candidates under development utilize adenovirus serotype 5 (Ad5) vectors to transport HIV antigens into cells in order to generate HIV-specific cellular immune responses. Although adenoviruses are known to cause the common cold, Ad5 vaccine vectors have been weakened to make them replication-incompetent and thus safe for use as vaccines. According to Dr. Barouch, a potential limitation of Ad5 vectors is that the majority of individuals, particularly in sub-Saharan Africa, have pre-existing immunity against the Ad5 vector, which could neutralize Ad5 vaccine vectors before they have a chance to do their job.

The scientists observed that the majority of Ad5-specific antibodies target the major hexon capsid protein. The hexons outer surface consists of loops known as hypervariable regions and the scientists swapped the hexon surface loops with the corresponding regions from the rare adenovirus serotype Ad48. The novel chimeric vector retained many desirable features of Ad5 vectors but was not inhibited by pre-existing immunity against Ad5 in both mice and rhesus monkeys. Moreover, the chimeric vector generated strong immune responses against the vaccine antigen: the Gag protein from simian immunodeficiency virus. According to Dr. Barouchs group, plans to explore whether this vector can be developed further into clinical trials as a potentially improved HIV-1 vaccine candidate.


Researchers make vitamin E offshoot a potent cancer killer

In the United States, researchers led by Dr. Ching-Shih Chen, professor of pharmacy and internal medicine at the Ohio State Universitys Comprehensive Cancer Centre, have learned how a derivative of vitamin E causes the death of cancer cells. The researchers then used that knowledge to make the agent an even more potent cancer killer. The compound, called vitamin E succinate or alpha tocopheryl succinate, is taken by some people as a nutritional supplement, mainly for its antioxidant properties. In addition, it has a weak ability to kill cancer cells, and it has been tested as a cancer chemo-preventive agent. It kills cancer cells by causing them to undergo apoptosis. Until now, no one knew how the agent caused this to happen.

Dr. Chen and colleagues found that vitamin E succinate worked by blocking a protein called Bcl-xL. The protein, which is made by healthy cells, is often present at abnormally high levels in cancer cells and protects them from dying when they should. Using computer modelling, the researchers found that the vitamin E derivative works because it lodges in a groove in the structure of the Bcl-xL protein, disabling it. However, the vitamin E molecule has a long, protruding, coiled tail that keeps the molecule from fitting tightly, and more effectively, into the groove. The scientists found that altering the molecules structure by cutting the tail short allowed a tighter fit and improved the agents ability to kill cancer cells by five- to ten-fold in laboratory tests. According to Dr. Chen, the findings are proof of the principle that this drug can kill cancer cells very effectively but does very little damage to healthy cells and could lead to a potent chemo-preventive agent that has both strong anti-cancer and antioxidant properties.


Research brings cheap anti-malarial drug nearer

A process to create a less expensive version of artemisinin, a life-saving anti-malarial drug, has been developed by Dr. Jay D. Keasling, University of California Berkeley, the United States. His lab partnered with the San Francisco-based Institute for OneWorld Health, a non-profit pharmaceutical company, and Emeryville-based Amyris Biotechnologies to develop low-cost artemisinin drugs using Dr. Keaslings genetically engineered microbes.

In 2004, Dr. Keaslings team succeeded in engineering bacteria to make a chemical precursor of artemisinin. The teams ultimate goal was to retool the microbes metabolism to perform as much of the drug synthesis as possible in order to side-step the expensive laboratory synthesis needed to make artemisinin. That synthesis would have increased the drugs cost beyond the researchers ambitious target of US$0.25 per dose. They now have nearly achieved that goal by engineering the production of artemisinic acid, one chemical alteration away from artemisinin. According to Dr. Keasling, this is probably as close to artemisinin as the scientists could get in microbes and the rest is going to be done by chemistry.

The teams work accelerated when they identified the enzyme and the gene in wormwood from which artemisinin is currently extracted that chemically changes amorphadiene into artemisinic acid. The enzyme, a member of a large family of cytochrome P450 enzymes, attaches itself to internal cell structures not present in bacteria, so Dr. Keaslings team tried first to make it work in yeast. The researchers used some of the yeasts own genes, plus bacterial genes and wormwood genes inserted into the yeast genome. With the added wormwood gene for the P450 enzyme, the yeast manufactured the desired chemical, artemisinic acid. The yeast produces perhaps one-tenth the amount of amorphadiene as the current version of the engineered bacteria, so its output of artemisinic acid is still relatively low. However, according to Dr. Keasling, it is just a matter of time before they have a microbe ready for scale-up to production.


Cruciferous vegetables and genetic cancer

A research team led by Dr. Ah-Ng Tony Kong at Rutgers, the State University of New Jersey, the United States, has revealed that cruciferous vegetables like broccoli and cauliflower are abundant in sulforaphane (SFN). This compound had previously been shown to inhibit some carcinogen-induced cancers in rodents. Dr. Kongs research focused on whether SFN might inhibit the occurrence of hereditary cancers.

Chemo-preventive properties are those that stop, reverse or prevent, the development of cancer. Dr. Kong and his colleagues used a mouse model for human colon cancer to demonstrate the chemo-preventive power of SFN and explain how it works to thwart cancer at the biomolecular level. The researchers employed a specially bred strain of mice (labelled Apc/Min/+), which carries a mutation that switches off a tumour-suppressing gene (Apc). This is the same gene known to be directly associated in the development of most colon cancers in humans. When the gene is inactivated in the mice, polyps, which lead to tumours, appear.

Two groups of mice were fed diets supplemented with SFN for three weeks, one group receiving 300 ppm of SFN and the other getting 600 ppm, while the control group did not receive any SFN. The results clearly demonstrated that those mice fed with an SFN-supplemented diet developed significantly fewer and smaller tumours. After the three weeks, the average number of polyps in the small intestine in each mouse decreased more than 25 per cent in those on the 300 ppm diet and 47 per cent in the 600 ppm treatment group, as compared with control animals.

Using biomarkers associated with apoptosis and proliferation, Dr. Kongs team found that SFN suppressed certain enzymes or kinases that are highly expressed both in the mice and in patients with colon cancer. The researchers concluded that this enzymatic suppression activity is the likely basis for the chemo-preventive effects of SFN. According to Dr. Kong, SFN should be evaluated clinically for its chemo-preventive potential in human patients with Apc-related colon cancers.


One big biology question solved

An Australian research team, led by Dr. Josephine Bowles and Professor Peter Koopman from the Institute for Molecular Bioscience at the University of Queensland, has solved one of biologys most fundamental questions: why males produce sperm and females produce eggs. The team has discovered that the Vitamin A derivative, retinoic acid, triggers the beginning of egg and sperm production, a process known as meiosis. They also discovered an enzyme present in male embryos that wipes out retinoic acid and so suppresses meiosis until after birth, resulting in sperm production.

The germ cells that eventually turn into either eggs or sperm are identical in male and female embryos. According to Prof. Koopman, whether a germ cell develops into an egg or a sperm is dependent on the time at which meiosis begins. In females, meiosis begins before birth and eggs are produced, whereas in males, meiosis begins after birth and the result is sperm. Knowledge of what triggers and suppresses meiosis may allow researchers to improve fertility, for example, in the case of an infertile couple wanting a baby, or suppress it, in the case of pest management. Prof. Koopman also suggests that an inappropriate retinoid signal might give the wrong instructions to germ cells, leading to the formation of germ cell tumours.


A new genetic cause of Alzheimers disease

Amyloid protein has already been known to be the primary component of the senile plaques in the brains of patients. Researchers from the Flanders Interuniversity Institute for Biotechnology con-nected to the University of Antwerp, Belgium, have now shown that the quantity of amyloid protein in brain cells is a major risk factor for Alzheimers disease. The discovery demonstrates that the greater the quantity of the protein that is produced, the younger the dementia patient is and higher the risk of contracting Alzheimers.

Amyloid protein originates when it is cut by enzymes from a larger precursor protein. In very rare cases (fewer than 1 in 1,000 patients), mutations appear in that amyloid precursor protein, causing it to change shape and be cut differently. The amyloid protein thus formed has different characteristics, causing it to begin to stick together and precipitate as amyloid plaques. The development of amyloid plaques in the brain tissue of Alzheimer patients is a central factor in the search for a therapy for Alzheimers disease.

Researchers found genetic variations in the promoter that increased the gene expression and thus the formation of the amyloid precursor protein. These variations in the promoter that increase expression occur up to 20 times more frequently (2 per 100 patients) than the mutations in the precursor protein that change the shape. Patients with Downs syndrome have 3 copies of the gene for the amyloid precursor protein and therefore produce 150 per cent instead of 100 per cent of the protein, thus supporting the fact that patients with Downs syndrome get Alzheimers disease. Furthermore, researchers found connection with the age at which the symptoms are first detected: the higher the expression (up to 150 per cent as in Downs syndrome), the younger the patient (starting between 50 and 60 years of age). Thus, the amount of amyloid precursor protein is a genetic risk factor for Alzheimers disease in the ageing process.



Researchers find protein that silences genes

A team of researchers led by Dr. Craig Pikaard at Washington University in St. Louis, the United States, has discovered the key role one protein plays in the turning off of thousands of nearly identical genes in a hybrid plant. Studying the phenomenon of nucleolar dominance, in which one parental set of ribosomal genes in a hybrid is silenced, the scientists identified the protein HDA6 as an important player in the silencing, using the experimental plant genus Arabidopsis.
According to Dr. Pikaard, genes can be turned off when acetyl groups are removed from histones, the proteins that wrap the DNA, and when methylation of cytosine, one of the four chemical subunits of DNA, occurs. He and his collaborators found that one of many predicted histone deacetylases in Arabidopsis, HDA6, is a key player in both histone deacetylation and DNA methylation of ribosomal RNA genes. In plants, as well as animals, some epigenetic traits are stable and can be inherited when a cell divides.

In their study, Dr. Pikaard and his collaborators made transgenic hybrids in which each of the deacetylases were knocked out one by one and then examined the plants to see if there were effects on nucleolar dominance. In this process, they found that knocking down HDA6 eliminated nucleolar dominance, such that the normally silent genes were now turned on. The group then genetically engineered the protein to include a fluorescent tag and found that much of the HDA6, seen as a glowing red signal under the microscope, shows up in the nucleolus, which is precisely the site where ribosomal RNA genes are regulated and where nucleolar dominance occurs.

The scientists characterized HDA6 biochemically and demonstrated that it was a histone deacetylase, as predicted, and that the protein would remove acetyl groups from several different histones. They were able to confirm that the deacetylation specificities they observed for HDA6 in the test tube fit with the changes in acetylation that occur on ribosomal RNA genes in living cells. They also found that the mechanism behind the silencing involves modifications of histones and changes in DNA methylation, and that HDA6 affects both.

Understanding how some genes are selectively silenced and how silenced alleles can be turned on again may someday have practical benefits.


Newly discovered protein could help prevent heart disease

Researchers led by Dr. Pappachan Kolattukudy, dean of the University of Central Floridas Burnett College of Biomedical Sciences, the United States, have discovered a new gene known as MCPIP that could provide scientists with the key to developing treatments for preventing inflammation that can cause heart disease.

The team found that the levels of MCPIP increased in mice as their blood vessels became inflamed and heart disease began to develop. The formation of MCPIP leads to the death of healthy cells, so treatments that block that formation could prove effective for heart disease.

MCPIP is formed when a protein called MCP-1 binds to receptors. The MCP-1 protein helps to attract white blood cells known as monocytes to infected and injured areas of the body. The monocytes then attack bacteria and help the body fight diseases. But that process also produces several known and unknown proteins. The researchers focused on MCPIP, one of the previously unknown proteins, because of the links between it and the death of healthy cells adjacent to the infected ones.

The laboratory mice developed heart disease in a way similar to how it forms in humans, which suggested that the findings could hold promise for treating human heart disease. The research team already has found that MCPIP is elevated in human hearts suffering ischemic heart failure.


Mechanism for essential genome-wide gene silencing identified

Dr. Shelley L. Berger, at the Wistar Institute, the United States, and colleagues have identified an important new global mechanism for essential gene silencing, or gene repression. Reliable gene silencing is vital to the health of an organism. Improperly activated genes can and do lead to cancer, for example. Gene silencing is also thought to protect the genome from viruses and other potentially damaging entities, thus preserving genetic integrity.

The newly discovered mechanism centres on histones, relatively small proteins around which DNA is coiled to create structures called nucleosomes. Compact strings of nucleosomes then form into chromatin, the substructure of chromosomes. In the study, conducted in yeast Saccharomyces cerevisiae, the scientists showed that a protein called SUMO binds to histones and acts to repress transcription of genes, and it does so at many different sites across the genome.

The research team also noted a dynamic interplay between the addition of a SUMO protein to a histone (sumoylation) and the addition of either an acetyl group or a ubiquitin protein to a histone. The processes appear to be mutually exclusive. Acetylation and ubiquitylation have been earlier shown to activate gene expression.

Another observation made during the study was that slightly higher levels of sumoylation occur near the tips of the chromosomes, the telomeres, which are known to play a key role in maintaining genomic stability. The findings are important, as gene-regulation strategies first observed in yeast and other lower-order organisms are often found in mammalian cells also.


Scientists unlock more secrets of HIV and SARS

Scientists led by Dr. Ian Brierley at the University of Cambridge, the United Kingdom, have cracked one of the key biological processes that viruses such as HIV and SARS use when they replicate. Viruses are able to interfere with the host cell processes that our bodies use to replicate cells, and protein synthesis is often one of their targets. For the first time, the researchers have witnessed virus-induced frame-shifting in action and have been able to identify the crucial role of particular elements. This collaborative project was set up with Dr. Robert Gilberts team in Oxford to investigate the structure of a frame-shifting ribosome using electron microscopy.

The scientists have revealed the workings of the process known as ribosomal frame-shifting that forces a misreading of the genetic code during protein synthesis. The correct expression of most genes depends upon accurate translation of the frame of the genetic code, which has a three-nucleotide periodicity. Viruses such as HIV and SARS bring into the cell a special signal that forces the ribosome to back up by one nucleotide, pushing it into another frame and allowing synthesis of different viral proteins. These are exploited by viruses and help them to survive and multiply. The researchers imaged frame-shifting in action and for the first time observed how a virus-encoded element called an RNA pseudoknot interferes with the translation of the genetic code to allow viruses like HIV and SARS to express their own enzymes of replication.


Entire active protein inventory in cells mapped

Led by Dr. Matthias Mann from the Max Planck Institute of Biochemistry in Germany, researchers from Canada, China, Denmark, Germany and the United States have catalogued the entire inventory of active proteins in cell organelles at a particular moment. Using mass spectrometry, and by comparing databases, the scientists detected more than 1,400 proteins, localized in ten different cell compartments, in the liver cells of mice. Certain proteins assign themselves clearly to particular cell organelles. When the scientists took the protein complex apart, these proteins were used as markers.

Proteins that appear together with these marker-proteins could now be assigned their proper place in the inventory a method called protein correlation profiling.
After the individual compartments for the proteins were identified, the scientists compared corresponding protein sets of individual cell organelles. Among the 1,400 different proteins that can be clearly mapped onto individual cell organs, 40 per cent also appear in other cell organs. When compared with yeast cells, their proteins have stayed true to their cell organelles over the course of evolution over almost a billion years, as simple organisms evolved all the way to mammals. For the first time, the scientists were able to determine where in the cell large numbers of proteins belong, and form a new understanding of their function and interactions.



Single gene is both friend and foe to rice

Dr. Wang Shiping and colleagues at the Huazhong Agricultural University in Wuhan, China, have found that one rice gene regulates both the plants fertility and its ability to resist bacterial leaf blight, one of the plant worlds most devastating bacterial diseases. The newly discovered gene can have both positive and negative effects. The most common form of the gene makes rice plants more susceptible to bacterial leaf blight but also makes them produce more pollen. According to Dr. Wang, one way for researchers to maximize the genes benefits would be to block its activity in leaves while boosting it in flowers. The finding could help scientists develop rice varieties with higher yields and better disease resistance.

In a separate study, researchers led by Dr. Zhu Lihuang of the Chinese Academy of Sciences genetically modified rice to resist the single most important rice disease, rice blast disease caused by a fungus Magnaporthe grisea. Dr. Zhus team modified rice plants employing a local variety that resists all 156 Chinese and Japanese strains of the fungus.


Plant protection from cold decoded

Scientists from the University of California, Riverside, the United States, and Institute of Genetics and Development of the Chinese Academy of Sciences in Beijing, have found that in response to cold, plants trigger a cascade of genetic reactions that help them survive. This negative regulator, known as high expression of osmotically responsive gene 1 (HOS1), acts as a biochemical gate that cuts off the plants cold protection. The HOS1 gene product interacts with another gene product known as ICE1 that kicks off the genetic cascade, which provides the plants cold protection proteins. The interaction worked both in the test tube and in live plant.

According to Dr. Jian-Kang Zhu who led the study, these responses are all related from a genetic and molecular standpoint. Some of the same genes are involved in all of these responses and understanding how they work can help scientists develop crops that can better withstand these conditions. The discovery of how HOS1 acts on plants should help the research efforts into how plants respond to environmental stresses such as cold, soil salinity and drought. This process should apply to all plants and can help in the better use of crops of subtropical origin such as avocados, rice, corn and strawberries.


Study says GM cotton cuts pesticide application

A study led by Dr. Yves Carrire of the University of Arizona, the United States, has concluded that genetically modified (GM) cotton can offset some of the environmental impacts of intensive agriculture by reducing pesticide use. The study is the largest of its kind to date. It also showed that cotton carrying a bacterial gene for a toxin that kills the crops main insect pest had no significant effect on non-target species. Researchers in India had warned last year that Bt cotton grown there was not effective at killing bollworms, and that farmers had to spray more insecticide as a result.

The new study compared conventional cotton with two GM varieties. One had a bacterial gene that produces toxin, which kills the main insect pest of cotton, the bollworm, when it feeds on the crop. The other GM variety had an additional inserted gene that confers herbicide resistance, allowing farmers to control weeds without harming the cotton. The researchers compared the amounts of insecticides and herbicide farmers used, and the amount of cotton produced in 81 fields growing the different types of cotton. Overall the three varieties had similar yields, but farmers growing conventional cotton had to use extra insecticides to control the bollworm and other insect pests. Farmers used similar levels of herbicide for all three types of cotton.

According to the researchers, the findings indicate that Bt crops could be useful to reduce the environmental impacts of agricultural intensification. But they point out that this depends on whether farmers need to use insecticides to control insects unaffected by the Bt toxin. They emphasise that farmers should consider all key crop pests and means of controlling them when they are deciding whether to use Bt crops to reduce the impacts of agricultural intensification.


Ancient genes dictate flowering

Scientists at Swedish and United States universities have discovered genes that are responsible for initiation of flowering. The genes Constans (CO) and Flowering Locus T (FT) induce flowering in the annual plant Arabidopsis in response to day length. It was found that Populus trees (aspens, cottonwoods, poplars) also have CO and FT genes and can be forced to flower in months, rather than years.

Dr. Ove Nilsson and colleagues at the Umea Plant Science Centre, Swedish University of Agricultural Sciences, looked at a poplar homologue of the gene FT, which has been shown to regulate flowering in annual plants. They found that this gene not only controls the multi-year delay in flowering in trees, but also controls seasonal growth cessation and bud set. The Swedish scientists over-expressed FT in poplar, and observed normal flowers on six-month old trees, in a tree species that ordinarily takes 8-20 years to flower.

In order to understand why it take trees many years to flower, the American scientists Dr. Amy Brunner from Virginia Tech and Dr. Steven Strauss from Oregon State University used consecutive years of poplar clones to study the multi-year delay in flowering. They discovered that the expression of the FT gene increases with age, which according to Dr. Brunner might be part of the mechanism by which trees become adults.

The Umea Plant Centre scientists also looked at the genetics that signal fall growth cessation and bud set in trees. They discovered that CO accumulates in response to long days and initiates the formation of FT, and in the short days of fall, the pattern of CO accumulation changes so that FT is not activated. They also observed that the same species of tree at different latitudes would respond to local conditions in order to become dormant before the risk of frost damage. Because the short day-lengths occurring in fall induce bud set, the scientists wondered if FT and CO also controlled this process. When they grew trees originating from different latitudes in Europe in a growth chamber, the Umea Plant Centre team observed that this response was under strong genetic control and was maintained when trees were moved. However, they did observe that levels of CO and FT genes could be made to respond to artificially imposed day-length. Most importantly, they observed that under the same day-length, CO and FT levels accumulated differently in trees from northern latitudes compared to those from southern latitudes.


Kenya advances on GM cotton

Currently, research on the Bacillus thuringiensis (Bt) cotton, being undertaken at the Kenya Agricultural Research Institute (KARI) farm in Mwea, is at the stage of contained field. The Bt sub-species being used in the trials, kurstaki, is active in controlling a number of Lepidotera insects and pests in field plantations. The aim of the trials is to establish the efficacy of the protein variety, Cry IA(c), on the target insects under field conditions where pest pressures are experienced.

The main objectives of the project, which is expected to take about four months, is to evaluate the efficacy of Bt on cotton bollworms, study the effect of Bt on natural enemies and other non-target arthropods and to evaluate the risk of intercropping with Bt cotton. It also seeks to evaluate economic advantages of Bt cotton. During the trials, several biosafety safeguard measures have been put in place. Most of the material from the trial will be destroyed on site. Follow-up inspection will be done 2, 6 and 12 months after the initial trial, and no cotton will be planted on the trial site in the following year. The trial sites will also be inspected periodically by members of the National Biosafety Council (NBC) and Kenya Plant Health Inspectorate Service (KEPHIS).



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