VATIS Update Biotechnology . Sep-Oct 2008

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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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India to have a new facility for agri-biotech research

The International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) is collaborating with India’s Department of Biotechnology (DBT) under the Ministry of Science & Technology to establish a Platform for Translational Research on Transgenic Crops (PTTC) at the global headquarters of ICRISAT near Hyderabad in India. The project was recently approved by DBT with a funding commitment of Rs 248.79 million (US$6.25 million) for five years (2008-2013).

According to the Director General of ICRISAT, Dr. William Dar, the PTTC will strengthen transgenic research for crop improvement by providing a platform, building synergies among institutions. The mission of PTTC will be to “translate transgenic technology and harness its products to meet the needs of agricultural growth”.

The aim of establishing PTTC is to facilitate a co-ordinated approach for the translation of existing genetic engineering technologies in developing transgenic crop varieties for product development and commercialization. PTTC will evaluate and advance the potential of new genetic engineering options to enhance agricultural productivity. It will also provide expertise and facilities for the production and assessment of transgenic crop plants developed through collaborative projects. PTTC will serve as a facility of reference to strengthen national, regional and international linkages and collaboration in transgenic research and development, exchange of materials and information, as well as support training, consultation and technology commercialization.


Nepal to focus on biotech, biofuel research

Nepal’s new government is planning a US$125 million science budget for 2008 – a staggering 12-fold increase from last year. The money will go to the Ministry of Environment, Science and Technology (MEST), with biotechnology research being a focus – primarily to exploit Nepal’s rich biological resources. A biotech lab in Kathmandu is due to be completed in 2009, while MEST plans to construct a national biotechnology research and development centre. As Nepal often faces electricity and petrol shortages, the government will also earmark a large part of the money to developing clean energy, including the use of a jatropha as a biofuel.


Industrial biotech revenues to touch US$125 billion by 2010

McKinsey & Company presented latest data and projections for adoption of industrial biotechnology within the biofuels and chemicals industries at the third annual World Congress on Industrial Biotechnology and Bioprocessing. It predicts that by 2010 industrial biotechnology will account for 10 per cent of sales within the chemicals industry, accounting for US$125 billion in value.

As of 2005, industrial biotechnology, counting products made from bio-based feedstock or through fermentation or enzymatic conversion, accounts for seven per cent of sales and US$77 billion in value within the chemicals sector. The spurt in projected growth industrial biotechnology is attributable to biofuels – ethanol and biodiesel – as the production is rapidly increasing to meet demand driven by government mandates. Other areas projected to grow rapidly include pharmaceutical ingredients, polymers and enzymes.


China’s huge push to GM crops

China is set to launch a US$3.5 billion research project for genetically modified (GM) crops to help address the demand for food in the world’s most populous nation. Exact details of the initiative are yet to be worked out, but the State Council approved it in July, after Premier Mr. Wen Jiabao told senior scientists that the country needs “big science and technology measures” like GM to solve its food problem.

The new initiative will also include a public education initiative to try to ease public safety concerns over GM. Chinese scientists say that legitimate concerns over GM crops’ biosafety should not be used to mislead the public in the name of environmental protection. China has already widely planted insect-resistant GM cotton, which occupies 70 per cent of the area devoted to growing the crop in China. Chinese scientists have also successfully developed several types of GM rice, but the government has delayed commercialization of GM rice because of biosafety concerns.


GM banana trials get the green light in Australia

Australia’s first genetically modified bananas will be planted in Far North Queensland, following approval from the Office of the Gene Technology Regulator. Two trial crops will be planted near by the Queensland University of Technology (QUT) – one with nutrient-enhanced bananas and the other with disease-resistant Cavendish bananas. QUT Professor Dr. James Dale says the trials are the next step in the path to commercial production. “Bananas are extremely difficult to breed conventionally,” he says, adding, “This kind of technology offers the opportunity to improve bananas significantly.”


Bioenergy research receives a boost in Brazil

Brazilian bioenergy research has received a boost with the launch of a new research programme promoting cooperation between academic institutions and industry. Bioenergy Research Programme (BIOEN), run by the State of São Paulo Research Foundation (FAPESP), is expected to gain US$130 million of investment over the next five years. The programme will receive an initial investment of US$46 million provided by FAPESP, the National Council for Scientific and Technological Development, the State of Minas Gerais Research Foundation and Dedini, one of the private companies involved.

BIOEN will fund research on plant improvement and sugarcane farming, ethanol industrial technologies, bio-refinery technologies and alcohol chemistry, ethanol applications for motor vehicles, as well as research into the social, economic and environmental impacts of using and producing biofuels. Brazil currently produces 35 per cent of the world’s ethanol, and about 62 per cent of this is produced in São Paulo.

Besides academic activities, BIOEN will work with private companies in Brazil’s bioethanol industry to bring new technologies to industry sooner. It will also identify market needs and select scientific institutions to address them. Although FAPESP expects many of the projects to be on ethanol, the programme is open to funding research on other forms of bioenergy, such as biodiesel and biogas. They are also open to social research that investigates, for example, working conditions in the sugar cane industry and the impacts of mechanization of the harvest.


Pakistan launches national biosafety body

Pakistan has established the Pakistan Biological Safety Association (PBSA), a national-level body to monitor biosafety measures in biotechnology and trans-border infectious diseases. PBSA was launched by the Higher Education Commission’s National Core Group in Life Sciences. It includes officials from the country’s R&D establishments, and will act as a watchdog to monitor observance of biosafety standard in laboratory work on microbes, pathogens and transgenic materials. It will also conduct awareness campaigns on biosafety issues.

PBSA will report any violations to the Biosafety Directorate of the Ministry of Environment, which had established a set of biosafety guidelines in 2005. PBSA’s first aim is to conduct a vaccine awareness campaign among farmers on avian influenza, as Pakistan has seen cases of H7 and H9 strains of bird flu in poultry. It also wants to introduce biosafety as part of the national curriculum at university level.


Plans on the anvil to make India a biotech power

Mr. Kapil Sibal, India’s Minister for Science and Technology and Ocean Development, indicated plans of building new institutions and strengthening some of the existing ones to world class standards in the area of biotechnology. Addressing a press conference at the foundation day function of Biotechnology Department, he outlined the proposals to make India a biotechnology power in future. These include establishment of a centre for translational research in health science at Faridabad in the northern state of Haryana. The centre will develop new vaccines, futuristic diagnostics and biological drugs, establish an incubator for development of products, and build capacity for running academic programmes.

The Minister said the Government is keen to set up a single Biotechnology Regulatory Authority for clearing biotech products. A committee has been constituted to work out modalities for the creation of the Authority and rationalization of the legislative and regulatory regime. There is also a proposal to award 25 special overseas fellowships for students doing research in stem cell technology and nano biotechnology.

Mr. Sibal informed that international collaboration programme has been reviewed and his Ministry would like to build strategic partnerships. A major programme for animal vaccines and immuno-stimulants for aquaculture has been firmed up with the Government of Norway. Another strategic collaborative agreement has been signed with Australia for collaboration in biotechnology. The Ministry has also entered into strategic partnership agreements with Denmark in agriculture and food biotechnology, with Finland in diagnostics and with United Kingdom in frontier biology.


South African farmers increase plantings of GM crops

The adoption of genetically modified (GM) crops in South Africa has been progressing steadily over the last decade due to significant on-farm economic benefits. In 2007, approximately 57 per cent of the total maize acreage in South Africa was planted with GM maize. The farmers grew more than 1.8 million hectares of GM crops – including maize, soybeans and cotton – last year, almost 30 per cent more acres than in 2006. A recent study by Brookes & Barfoot estimates that South African farmers have increased their farm income by US$156 million in the period 1998-2006 by using GM crops. High cost of inputs such as pesticides is one reason the farmers are turning to GM crops, while irregular supply of pesticides and low yields of conventional crops are the other aspects.

Source: www.greenbio.checkbio


MedMira gets China patent on rapid diagnostics

MedMira Inc., a Canada-based developer and marketer of rapid diagnostics, has announced that it received a ‘Notice on Grant of Patent Right for Invention’ from China’s State Intellectual Property Office for its rapid diagnostic device and assay. The novel invention is the rapid flow-through technology (RFT) platform, the core product engine upon which the company has built its successful line of rapid tests for diseases such as hepatitis and HIV. MedMira had earlier secured similar patents in the United States and the European Union.

Through straightforward and affordable licensing agreements MedMira offers its patented technology platform to diagnostics developers seeking a clear path to the global diagnostics market. The RFT technology is the core innovation behind MedMira’s fully commercialized line of rapid tests for diagnosing one or multiple diseases using one test device and a single drop of specimen.


U.S. Genomics bags contract for advanced biosensor

U.S. Genomics Inc. of the United States has bagged a US$9.1 million contract from the United States Department of Homeland Security (DHS) Science and Technology Directorate. The Phase IIIX contract under the Bioagent Autonomous Networked Detectors (BAND) programme will enable U.S. Genomics to continue development, testing and optimization of the company’s sophisticated biological sensor for the detection of airborne pathogens using single molecule DNA mapping technology.

“The resources provided under the contract will allow us to perform extensive operational testing and to advance the capabilities of our prototype systems,” said Mr. John J. Canepa, CEO of U.S. Genomics. The DNA mapping technology of the company allows very precise broadband detection of bacterial pathogens, toxins and viruses in a biological sample. The technology’s readings are sensitive to the single-molecule level and yield extremely low false positive rates.


Gene Bridges patents recombination technology in Japan and Mexico 

Gene Bridges GmbH of Germany has received patents in Japan and in Mexico relating to its recombination technology. The Japanese patent is entitled “Novel DNA Cloning Method” while the Mexican patent is entitled “Methods and compositions for directed cloning and sub-cloning using homologous recombination”. Both patents broadly cover the major areas of Gene Bridges’ Red/ET recombination technology, already covered by patents in the United States, European Union, Republic of Korea and Israel. Red/ET is a DNA engineering method. Recombination with Red/ET allows cloning, sub-cloning and modification of DNA at any chosen position. It permits precise engineering of DNA molecules of any size, including very large ones such as BACs or the E. coli chromosome, according to the company.


Research collaboration between Monsanto and Evogene

The global agri-business giant Monsanto Company and Evogene Ltd. of Israel have entered into a five-year collaboration in research and development focused on identifying key plant genes related to yield, environmental stress and fertilizer utilization. The agreement is intended to enhance research efforts to discover and deliver novel, yield-enhancing technologies at a time when the global grain demand is increasing.

Under the terms of this collaboration, Evogene will provide Monsanto with candidate genes discovered by Evogene’s computational platform that are predicted to improve yield, fertilizer utilization and a plant’s reaction to environmental stress. The genes will be validated in model plants. The collaboration will provide Monsanto access to new genes strengthening its entire gene discovery programme. Monsanto will receive exclusive licensing rights to such genes in a number of crops, such as maize, soybean, canola and cotton. Monsanto will evaluate the licensed genes in its R&D pipeline. Monsanto will commercialize the products that emerge from the joint development through its branded and licensed businesses.

Evogene expects to receive about US$35 million over the research term of the collaboration in the form of an upfront payment and annual research payments. Evogene is also entitled to development milestone and royalty payments based on sales of any resulting products. Monsanto believes this new collaboration will help support its commitment to double yields in its core crops by 2030. In a separate agreement, Monsanto has purchased US$18 million equity in Evogene and has agreed to purchase a further US$12 million in the future, subject to certain Evogene diligence requirements.


GSK commits US$25 million to stem cell alliance

GlaxoSmithKline (GSK) and the Harvard Stem Cell Institute (HSCI) are embarking on a five-year, US$25 million plus stem cell science collaboration. GSK’s investment will support research at the university and in at least four Harvard-affiliated hospitals in neuroscience, heart disease, cancer, diabetes, musculoskeletal diseases and obesity. In addition, GSK will fund an annual grant that supports early-stage research in stem cell biology as part of HSCI’s seed grant programme. The collaboration will integrate HSCI’s stem cell expertise with GSK’s pharmaceutical capabilities to drive advances in drug discovery research, according to the groups. This will include a staff exchange program. The collaboration will be overseen by a joint steering committee made up of HSCI and GSK scientists and managers.


Roche starts acquisition process of ARIUS Research  

The multinational healthcare company Roche has started acquisition of the Canadian biotechnology company ARIUS Research Inc. (ARI) in an all-cash transaction at a price of approximately C$ 191 million (about US$184.8 million). ARI is the developer of a proprietary antibody platform called FunctionFIRSTTM, which rapidly identifies and selects antibodies based on their functional ability to affect disease before progressing into clinical development.

According to the company, this platform will allow Roche to further strengthen its developmental portfolio, initially within the areas of oncology and inflammatory diseases where this new technique offers potentially broad therapeutic applications. “The FunctionFIRST approach provides us with a large library of antibodies from which we can identify the best new drug candidates for the development of clinically differentiated medicines,” said Mr. Lee Babiss, Head of Global Research at Roche. Roche will pay C$2.44 (US$2.36) for each common share of ARI.           


Bayer sues Sandoz over oral contraceptive drug

The multinational healthcare company Bayer AG based in Germany has filed a patent infringement lawsuit against Sandoz, a global generics leader belonging to the Switzerland-based Novartis, that sought approval of United States Food and Drug Administration (FDA) for a generic version of oral contraceptive drug YAZ. A Bayer spokesperson declined to give further details.

YAZ is the lower dose version of its contraceptive drug Yasmin. Bayer retains FDA marketing exclusivity for YAZ until March 2009. In June this year, Bayer agreed to supply a generic version of Yasmin for Barr Pharmaceuticals Inc. to market in the United States in return for a fixed portion of sales. Barr had challenged the Yasmin patent held by Bayer and in March, a United States district court found that the patent held by Bayer was invalid. Bayer has appealed against the ruling.



Kiwi fruit DNA sequences released

In New Zealand, researchers at the fruit science company HortResearch and the biotech company Genesis Research & Development Corporation Ltd. announced the public release of the world’s most extensive collection of kiwi fruit DNA sequences. The release comprises over 130,000 kiwi fruit gene sequences – referred to by scientists as expressed sequence tags (ESTs). These are DNA sequences from active genes in the plant – genes that govern such characteristics as flavour, colour, shape, vitamin content and aspects of fruit development such as ripening and shelf life.

HortResearch scientist Dr. William Laing says the kiwi fruit ESTs will be used by the company’s breeders to speed up development of new kiwi fruit varieties through Marker Assisted Selection (MAS) technique. In a MAS breeding programme, breeders use traditional crossing techniques to breed new varieties – which are then assessed for their commercial potential by searching their DNA for markers that indicate the presence of genes linked to desirable fruit traits, and ESTs are essential to identify the specific genes. Dr. Laing says it will help in breeding new commercial varieties that include some of the numerous health, flavour and colour characteristics found in wild kiwi fruit.


Insulin-producing cells can become stem-like cells

In Canada, Dr. Lawrence Rosenberg from the McGill University Health Centre together with Dr. Bernard Massie from the Centre hospitalier de l’Université de Montréal have shown in vitro that insulin-producing â-cells can return to a more primitive developmental state called stem-like cells. This process, known as “dedifferentiation”, highlights the plasticity of this cell type. This same result has also been validated for the three additional types of cells that, along with â-cells, make up the islets of Langerhans. These islet cells together produce insulin and the other hormones in the pancreas.

“At this stage, we can’t confirm whether the cells’ ability to turn into stem-like cells occurs naturally in a healthy pancreas, but the results are very encouraging for the development of regenerative therapies to fight diabetes,” Dr. Rosenberg said. The cells’ in-vitro plasticity opens up totally new paths of investigation into the underlying causes of diabetes, and will validate the development of innovative treatments.

This study is the latest in an extensive regenerative therapies research programme based on a peptide called Islet Neogenesis Associated Protein or INGAP. Dr. Rosenberg and his colleagues had demonstrated INGAP’s potential to induce new islet formation in the pancreas. Clinical trials with INGAP have already showed that it is possible to regrow new functional insulin-producing cells in diabetic patients. “We know that the peptide works, but we are still lacking certain theoretical bases to explain its mechanism,” said Dr. Rosenberg. “This finding will allow us to move ahead on firmer ground.”


Next-generation tool for visualizing genomic data

Scientists are collecting vast amounts of diverse genomic data with ever-increasing speed, but effective ways to visualize these data in an integrated manner have lagged behind the ability to generate them. To address this growing need, researchers at the Broad Institute, the United Sates, have developed the Integrative Genomics Viewer (IGV), a freely available visualization tool that helps users simultaneously integrate and analyse different types of genomic data, and gives them the flexibility to zoom in on a specific genomic region of interest or to pan out for a broad, whole-genome view.

“This new tool offers a Google Maps-like view of integrative genomic data,” said Ms. Jill Mesirov, Chief Informatics Officer and Director of Computational Biology and Bioinformatics at the Broad Institute. With IGV, researchers can choose a Google Maps-like “street view” of the As, Cs, Ts and Gs that make up the genome, but they can also simultaneously visualize additional layers of complex information about gene expression as well as sequence alterations, or mutations, in the genetic code. Other genomic details, such as copy number variation, chromatin immunoprecipitation data, and epigenetic modifications, can also be viewed in IGV.

Moreover, all these data types can be overlaid or superimposed to determine how changes at one level will affect another. Users can choose from a variety of display options, viewing their data as a heat map, histogram, scatter plot, or other formats of their choice. IGV is free and available to researchers via the Web. It promises to increase the flow of discovery in many areas of biomedical research.


Key allergy gene discovered

In Germany, scientists at the Helmholtz Zentrum München (HZM), together with colleagues from the Department of Dermatology and Allergy and the Centre for Allergy and Environment of the Technische Universität München (TUM), have pinpointed a major gene for allergic diseases. The gene was localized using cutting edge technologies for examining the whole human genome at HZM.

The newly discovered FCER1A gene encodes the alpha chain of high-affinity IgE receptor, which plays a major role in controlling allergic responses. The team of scientists led by Dr. Stephan Weidinger from TUM and Dr. Thomas Illig from HZM found that certain variations of the FCER1A gene decisively influence the production of immunoglobulin E (IgE) antibodies. IgE antibodies are normally used to protect against parasites, but in some environments elevated IgE levels are associated with allergic disorders.

In genetically susceptible individuals, the immune system becomes biased and produces IgE antibodies against harmless agents such as pollen, dust mites or animal hair. These IgE antibodies then work in conjunction with certain cells to get rid of the allergens, a process that gives rise to the symptoms of allergy such as allergic rhinitis (hay fever), atopic dermatitis or asthma. The researchers examined the genomes of more than 10,000 adults and children from across Germany to detect the genetic factors. Although research is in its early stages, the new knowledge on the regulation of IgE production does have the potential to guide the development of new drugs.


Gene found for deadly childhood cancer

Researchers from the United States, Italy and Belgium have found a gene that causes most inherited forms of neuroblastoma, a rare and deadly form of childhood cancer, and say the discovery points to new treatments. Mutations in a gene called ALK were strongly linked to neuroblastoma, the researchers reported. The disease causes 15 per cent of childhood cancer deaths, with just a 40 per cent survival rate.

“This discovery enables us to offer the first genetic tests to families affected by the inherited form of this disease,” said Dr. Yael Mosse of The Children’s Hospital of Philadelphia, who worked on the study. “Furthermore, because there already are drugs in development that target the same gene in adult cancers, we can soon begin testing those drugs in children with neuroblastoma.”

The researchers studied 20 families with children having neuroblastoma. They found mutations in the ALK gene that cause it to be constantly active in helping cells proliferate. After finding the ALK mutations in familial neuroblastoma, they looked at sporadic cases – those not occurring in families with a history of the disease. They found ALK mutations in 12 per cent of 194 tumour cases of children with the aggressive, high-risk form of the disease.


Structure of key epigenetic component identified

Scientists from the Structural Genomics Consortium (SGC), a non-profit international organization, have determined the 3-D structure of a key protein component, which is involved in enabling the epigenetic code to be copied accurately from cell to cell. Epigenetic code is a series of chemical switches that is added onto the DNA in order to ensure that the body cells can form different tissue types, such as liver and skin tissues, despite having identical DNA genetic code.

The importance of the nuclear protein UHRF1 in the copying of epigenetic code has been earlier established. The scientists believe that when the code is copied, UHRF1 ensures the accuracy of the process, like a proof-reader checks a typeset article before printing. The key element of UHRF1 involved in this “proofreading” process is known as the Set and Ring Associated (SRA) domain, but the exact mechanisms by which the SRA domain accomplishes this task were unclear.

Now, the structure of the key element of UHRF1 that facilitates this process has been revealed, thanks to SGC, by three studies. SGC, in keeping with its policy of making its data immediately and freely available, made the underlying information available in the Protein Data Bank in 2008. The availability of this information allowed the other groups to make more rapid progress in their own work. One of the studies is by a research team led by Professor Masahiro Shirakawa from Kyoto University, Japan, who openly acknowledged that the SGC data was crucial to his team’s study.


Genetic clues to HIV resistance

Simultaneous expression of certain versions of KIR3DL1 and HLA-B*57 genes – which has been linked with a reduced risk of HIV progressing to AIDS – also lowers the risk of HIV infection in exposed uninfected individuals, according to a group of researchers from Research Institute of the McGill University Health Centre and University of Montreal Hospital Centre, Canada.

The strongest protection from disease progression in KIR3DL1 homozygotes (3DL1 hmz) is the co-expression of HLA-B*57 and a set of KIR3DL1 genotypes (3DL1*h/*y) lacking low-expressing allotypes on natural killer cells. The scientists evaluated whether this allele combination could also influence resistance to infection. The genetic distribution of 3DL1*h/*y and HLA-B*57 was compared in 41 HIV-exposed uninfected and 186 HIV-infected KIR3DL1 homozygotes. It was found that 12.2 per cent HIV-exposed uninfected people and 4.3 per cent of individuals in the primary infection cohort expressed HLA-B*57. The percentage of 3DL1*h/*y carriers were similar in both cases. The 3DL1*h/*y-HLAB *57 combined genotype was more frequent in exposed uninfected individuals (12.2 per cent) than those with primary infection (2.7 per cent). It was thus concluded that the co-expression of 3DL1*h/*y and HLA-B*57 helps to lower the risk of developing HIV when exposed to the virus.



World’s first blood test for colorectal cancer screening

GeneNews Limited, Canada, has announced the launch of ColonSentryTM, the world’s first blood-based molecular test for screening colorectal cancer. ColonSentry is a blood test that assesses a patient’s current risk of having colorectal cancer, identifying those with increased risk so that they might benefit from more invasive diagnostic tests such as colonoscopy. This risk stratification approach allows for a more targeted application of colonoscopy, which could increase the detection rate of colorectal cancer by as much as three-fold in an asymptomatic general population. The test requires a simple blood sample. The mRNA expression of a panel of seven specific genes is measured at the molecular level by quantitative RT-PCR, which results in an assessment of the patient’s current risk.


Research exposes new target for malaria drugs

Malaria parasites (plasmodia), once inside their human hosts, first set up shop in liver cells, then move into red blood cells (RBCs) to replicate and wait for the next mosquito to help continue the cycle. After plasmodia infect a blood cell, they send out clusters of sticky proteins to the cell surface, enabling them to attach to blood vessels and escape destruction by the host’s spleen while they replicate. This can be especially problematic during pregnancy as malaria-infected RBCs congregate in the placenta (the source of food and oxygen for the foetus), creating health problems such as anaemia, low birth-weight, fever and more.

Targeting the sticky proteins with drugs is difficult, as plasmodia contain many different varieties, which they employ to evade the human immune system. However, certain parts of the protein have to remain constant for proper function. A study by Dr. Matthew Higgins from the Department of Biochemistry, University of Cambridge, the United Kingdom, created high-resolution 3-D structures of the malarial sticky protein, PfEMP1, to detail how plasmodia protect these conserved areas.

Dr. Higgins found that a variable region of this protein covers a section that is important for docking up with the placental wall. When the infected RBC gets close to chondroitin sulphate, a structural molecule on blood vessels, the variable region moves aside and ever so briefly exposes the binding region, just enough to allow anchoring to take place. Dr. Higgins suggests that targeting this conserved binding domain of PfEMP1 protein with pharmaceuticals that mimic chondroitin sulphate and expose this region might be a worthwhile approach to develop or hasten immunity.


New discovery in stem cell research

Researchers from the European Union-funded EuroStemCell project have shown that mouse embryonic stem (ES) cells are able to self-renew without the natural culture materials – such as feeder cells, conditioned media, hormones and serum extracts – that scientists have so far used to maintain them and grow stem cell lines. This discovery contradicts previously-held view that these materials provided the signals and instructions to stem cells keep to their undifferentiated ‘blank’ state, and could have wide-ranging implications for stem cell research.

Cells still need to be grown in a culture giving them the sugars and proteins needed to stay alive. However, the scientists were able to show that ES cells produce their own signalling molecules and that these signals are the key driving force behind differentiation. When one of these signalling molecules, Fibroblast Growth Factor (FGF) 4, is eliminated or blocked, the cells can remain in their undifferentiated state indefinitely.

“The new culture conditions will help us to understand the nature of the pluripotent state and how it might be manipulated to produce specialized cells in the laboratory,” explains, Dr. Jason Wray of the Wellcome Trust Centre for Stem Cell Research, and one of the authors on the paper. The research is expected to help the derivation of ES cells from other animals. The discovery is also tipped to have major implications for large scale production of specialized cells, such as brain, heart muscle and insulin producing cells, for future therapeutic use.


Safe and inexpensive alternative to antibiotics

Researchers at Karolinska Institute in Sweden and the Royal Veterinary College in London have jointly developed a system that eliminates the need for antibiotics and resistance genes in the engineering of industrial and medical products. The method involves safer, less costly alternatives and is well suited for the industrial production of many types of biofuels and biopharmaceuticals. The wide use of antibiotic resistance genes for the selection of recombinant bacteria could contribute to the spread of antibiotic resistance. The practice is particularly inappropriate for some intrinsically resistant bacteria and in vaccine production, and costly for industrial-scale production. The non-antibiotic systems available require mutant host strains, defined media or expensive reagents.

While working on gene targeting in bacteria, the researchers discovered that a well-known interaction between a cell membrane synthesis gene and the biocide triclosan could be exploited for strain selection. Surprisingly, triclosan selection performs better than conventional antibiotic selection. The new cloning vector, pFab, enabled selection by triclosan at 1 ìM. Interestingly, pFab out-performed the parent pUC19-ampicillin system in cell growth, plasmid stability and plasmid yield. In addition, while pFab and triclosan are toxic to host cells when used alone, in combination they enhance growth and plasmid production through a gene-inhibitor interaction. The model thus offers an alternative plasmid selection method based on essential gene over-expression, without the use of antibiotic-resistance genes and conventional antibiotics.


Detection of tuberculosis surrogate

Single-Particle Aerosol Mass Spectrometry, or SPAMS, an instrument originally designed for the detection of the malicious use of biological pathogens, has potential use in the public health sector to rapidly screen people for tuberculosis. A team of researchers at Lawrence Livermore National Laboratory (LLNL), the United States, has used this instrument to detect a tuberculosis surrogate, even when it was surrounded by sputum and mucus-like substances. The team was also able to differentiate between an avirulent strain of tuberculosis and a similar bacterium, Mycobacterium semegmatis.

“The reason we used two similar mycobacteria in our research is that tuberculosis-like symptoms in a patient could be caused by many bacterial infections, not just tuberculosis. So, we would like to differentiate between non-tuberculosis and tuberculosis infections,” said Dr. Kristl Adams, a LLNL post-doctoral biological physicist and the study’s lead author. “There is no current method for screening potential tuberculosis patients within minutes,” said LLNL physicist and co-author Dr. Matthias Frank. The researchers said they believe SPAMS could potentially detect the disease within five minutes with concentrated samples.


Spinal cord stem cells could be basis of new therapy

A scientist at MIT’s Picower Institute for Learning and Memory, the United States, has pinpointed stem cells within the spinal cord that, if coaxed to differentiate into more healing cells and fewer scarring cells following an injury, may lead to a non-surgical treatment for debilitating spinal cord injuries. The results of the work carried out by Dr. Konstantinos Meletis, a post-doctoral fellow at the Picower Institute, and colleagues at the Karolinska Institute in Sweden, could help provide some degree of mobility to the 30,000 people worldwide afflicted each year with spinal-cord injuries.

The stem cells in the adult spinal cord proliferate slowly or rarely, and fail to promote regeneration on their own. But recent experiments show that these same cells, grown in the lab and returned to the injury site, can restore some function in paralysed rodents and primates. In the current study, the researchers found that neural stem cells in the adult spinal cord are limited to a layer of cube- or column-shaped, cilia-covered cells called ependymal cells. These cells form the thin membrane lining the inner-brain ventricles and the connecting central column of the spinal cord.

The study, by identifying for the first time where ependymal cells are found, paves a path towards manipulating them with drugs to boost their ability to repair damaged nerve cells. Upon injury, ependymal cells proliferate and migrate to the injured area, producing a mass of scar-forming cells, plus fewer cells called oligodendrocytes. The oligodendrocytes restore the myelin (coating) on nerve cells’ electrical impulse-carrying projections called axons. The failure of severed axons to regrow and reconnect with their target cells in the peripheral nervous system is one of the reasons for the limited functional recovery typically associated with central nervous system injuries.



Putting a hold on flu virus replication

Researchers at the Yokohama City University in Japan have gained a better understanding how influenza viruses replicate, possibly opening the way for the development of drugs to hamper their reproduction. The researchers zeroed in on an enzyme that flu viruses need to replicate and managed, for the first time, to capture a snapshot of the enzyme. Enzymes in influenza viruses are made up of three proteins bound tightly together.

The researchers crystallized the proteins and got a peek at part of the structure, which involves the tip of one of the proteins coming into contact with another protein. “This gives us some hope that we can interrupt this interface,” said Dr. Jeremy Tame, a member of the research team. Such an interruption would “kill the virus, or slow it down sufficiently,” he added. All influenza-A viruses, including the H5N1 bird flu virus, are believed to have similar structures. Theoretically, one drug could fight all of them.


New drug target against breast cancer

A team of scientists at Cold Spring Harbour Laboratory (CSHL), the United States, has identified an enzyme called Brk that may serve as a target for future drugs developed to fight ErbB2-positive tumours. Researchers claim that Brk helps these tumours become virulent and is also implicated in the process through which the tumours develop drug resistance. “The limited success of existing therapy suggested that factors besides ErbB2, or proteins that collude with ErbB2, might nullify the effects of Herceptin and Lapatinib,” explained CSHL Professor, Dr. Senthil Muthuswamy, leader of the research team and corresponding author of the paper. Herceptin and Lapatinib are tumour suppressors.

A detailed analysis of changes that occurred in the genomes of a sample of breast cancer patients helped the researchers confirm that the expression of ErbB2 and Brk was directly linked. By forcing the production of both ErbB2 and Brk within the same cell, they determined how Brk enhances ErbB2 activity and fortifies tumour cells against ErbB2-targeting drugs. The findings may suggest a way to treat patients with advanced ErbB2-positive tumours and those who have developed resistance to ErbB2 inhibitors.

According to the scientists, targeting Brk is a safe strategy because “Brk does not promote the proliferation of normal cells, and its expression in normal tissues is restricted to non-proliferating cells.” Inhibiting this protein might thus “produce fewer unwanted side effects than (targeting) other cancer-promoting proteins” that may be present in larger numbers.


Flower power against cancer

Prof. Eliezer Flescher and his colleagues of The Sackler Faculty of Medicine, Tel Aviv University, Israel, have developed an anti-cancer drug based on a decade of research into the commercial applications of the compound jasmonate, a synthetic compound derived from jasmine flower itself. Both blood cancers and solid tumours have been found to be responsive to the jasmonate compound, known also as methyl jasmonate. Prof. Flescher refers to this as the “jasmonate scaffold”, a basis for developing a series of chemical derivatives.

In terms of bioavailability and safety, early first-in-man studies have been proved successful, and Prof. Flescher is hopeful that an anti-cancer drug based on jasmonate could be on the shelf soon. “The jasmonate compound is used widely in agriculture and in cosmetics,” observes Prof. Flescher. “Proven to be non-toxic, it has the same regulatory status as table salt. That and the fact we are working on a natural chemical gives us a good starting point for launching a new drug.”



New protein survey upends understanding of apoptosis

Results from a study at The Scripps Research Institute (TSRI), the United States, have nearly tripled the number of proteins associated with the critical process of apoptosis, or programmed cell death, and have disproved a long-held idea about the life cycle of proteins. The research focused on proteolysis, the act of enzymes breaking down larger proteins into smaller components. The research team led by Dr. Benjamin Cravatt, chair of the Chemical Physiology Department at TSRI, wanted to begin filling in the many gaps in the understanding of proteolysis, including the full range of proteins broken down during specific cellular processes and what happens to the protein fragments.

The method developed, Protein Topography and Migration Analysis Platform (PROTOMAP), combines cutting-edge technologies in a powerful way. Dr. Cravatt and his colleagues processed samples of cells undergoing apoptosis, as well as control samples of intact cells, using electrophoresis. The scientists then sliced gels at set intervals and used mass spectrometry to identify the proteins found in each slice.

A key aspect of PROTOMAP is a new bioinformatics tool that the group devised to analyse mass spectroscopy data and presents it in a way that is readily interpretable and searchable. PROTOMAP enabled the scientists to access broad views of the entire landscape of proteins in the cells studied and to discern patterns that were completely unexpected.


Protein found to identify malignant melanoma

Researchers from the University of Rochester Medical Centre (URMC), the United States, found a new protein produced excessively in malignant melanoma. The protein, IMP-3, is over-expressed in the most dangerous types of skin cancer and in thin melanomas, a subset of lesions that can be difficult to predict. “This protein may have a key role in helping us understand and distinguish between various types of melanocytic lesions,” said first author Dr. Jennifer G. Pryor, a third-year resident in the URMC Department of Pathology and Laboratory Medicine. IMP-3 is an insulin-like growth factor-II mRNA binding protein involved in cell proliferation and appears to play a role in tumour formation in a number of cancers.

The pilot study investigated 56 biopsied lesion samples from 48 adults. The lesions fell into the category of cutaneous melanocytic neoplasms, a diverse group that includes benign moles, Spitz nevi and malignant melanoma. Dr. Pryor and co-authors showed why IMP-3 might be an important tool for pathologists, as the protein is produced excessively in most melanomas, and overly expressed more often in metastatic melanomas. The protein is also over-expressed in rare cases of invasive thin melanomas. This is significant because while most thin melanomas have a good prognosis, some act more aggressively and at present there is no accurate way to distinguish between the types of thin lesions.


Key to virulence protein entry into host cells discovered

Scientists at the Virginia Bioinformatics Institute (VBI) at Virginia Tech, the United States, have identified the region of a large family of virulence proteins in oomycete plant pathogens that enables the proteins to enter the cells of their hosts. The protein region contains the amino acid sequence motifs RXLR and dEER and has the ability to carry the virulence proteins across the membrane surrounding plant cells without any other machinery from the pathogen. Once inside the plant cell, the proteins suppress the plant’s immune system, allowing the infection to progress. The work focused on the virulence protein Avr1b from the soybean plant pest Phytophthora sojae.

P. sojae infestation results in annual soybean losses estimated at US$1-2 billion worldwide. All oomycete species contain hundreds of genes that encode for virulence proteins that have the RXLR-dEER region. The virulence proteins enter the soybean host where they are capable of suppressing programmed cell death (apoptosis) in plants. By preventing this protective mechanism in the host, the virulence proteins ensure that the pathogen can establish an unassailable foothold in the plant tissue from which the pathogen can pursue its destructive path. Dr. Daolong Dou, the lead author of the article, commented: “Our findings finally nail down that mechanism and enable us to focus on how to block the entry mechanism.”


Biochemists manipulate fruit flavour enzymes

Biochemists at the University of Texas Medical School (UTMS), the United States, say the day may be coming when scientists will be able to fine-tune enzymes responsible for flavours in fruits and vegetables. In addition, it could lead to environmentally friendly pest control. UTMS Assistant Professor C.S. Raman and his colleagues report that they were able to manipulate flavour enzymes found in a popular plant model, Arabidopsis thaliana, by genetic means. The enzymes – allene oxide synthase (AOS) and hydroperoxide lyase (HPL) – produce jasmonate (responsible for the unique scent of jasmine flowers) and green leaf volatiles (GLV) respectively. GLVs confer characteristic aromas to fruits and vegetables.

Genetic modification of GLV production has many important implications. “For example, the aroma of virgin olive oil stems from the volatiles synthesized by olives. By modifying the activity of enzymes that generate these substances, it may be possible to alter the flavour of the resulting oils,” said Dr. Raman. “Our work shows how you can convert one enzyme to another and, more importantly, provides the needed information for modifying the GLV production in plants.”

The scientists made 3-D images of the enzymes, which allowed them to make a small, but specific, genetic change in AOS, leading to the generation of HPL. AOS and HPL are part of a super family of enzymes called cytochrome P450. Although AOS or HPL are not found in humans, there are related P450 family members that help metabolize nearly half of the pharmaceuticals currently in use. In plants, AOS and HPL break down naturally occurring, organic peroxides into GLV and jasmonate molecules.

“These insights led to the striking demonstration that a single amino acid substitution converts one enzyme into another, thereby showing how a single point mutation can contribute to the evolution of different biosynthetic pathways. This begins to answer a long-standing question, as to how the same starting molecule can be converted into different products by enzymes that look strikingly similar,” said Dr. Rodney E. Kellems, Chairman of the Department of Biochemistry & Molecular Biology at UTMS.


Protein structure discovery opens door for anti-virals

In the United States, scientists at Rutgers University and the University of Texas at Austin (UTA) have reported a discovery that could help develop drugs to fight the much-feared bird flu and other virulent strains of influenza. They have determined the 3-D structure of a site on an influenza-A virus protein that binds to one of its human protein targets, thereby suppressing a person’s natural defences to the infection and paving the way for the virus to replicate efficiently. This NS1 virus protein is shared by all influenza-A viruses isolated from humans, including avian influenza and the 1918 pandemic influenza virus.

About 10 years ago, Prof. Robert M. Krug at UTA discovered that the NS1 protein binds a human protein known as CPSF30, which is important for protecting human cells from flu infection. Once bound to NS1, the human protein can no longer generate molecules needed to suppress flu virus replication. Now, scientists led by Rutgers’ Professor Gaetano T. Montelione and Prof. Krug have identified the novel NS1-binding pocket that grasps the human CPSF30 protein.

X-ray crystallography carried out at Rutgers identified the 3-D structure of the NS1-binding pocket and gave the research team unique insights into how the NS1 and human protein bind at the atomic level, and how that suppresses a crucial antiviral response. Scientists at UTA verified the key role of this binding pocket in flu replication by genetically engineering a change to a single amino acid in the NS1 protein’s binding pocket, which in turn eliminated the protein’s ability to grasp the human protein that is needed to generate antiviral molecules. These investigators then produced a flu virus with an NS1 pocket mutation and showed that this mutated virus doesn’t block host defences, and therefore has a much reduced ability to infect human cells.


Protein key to control, growth of blood cells

New research using mice has shed light on the biological events by which stem cells in the bone marrow develop into the broad variety of cells that circulate in the blood. Haematopoietic stem cells (HSCs) develop into blood cells and, like other stem cells, have the ability to self-renew. A group of researchers led by Dr. Wei Tong, a haematology researcher at the Children’s Hospital of Philadelphia, the United States, focused on a protein called Lnk that helps control HSC expansion. When a growth factor in the blood called thrombopoietin (TPO) acts on its cell receptor, it triggers signals along a pathway that includes JAK2, another protein. JAK2, in turn, causes stem cells to increase their numbers.

Dr. Tong’s group found that mice genetically engineered to lack the Lnk protein had 10 times the normal amount of HSCs in their bone marrow. Without Lnk to directly interact with JAK2 and inhibit its activity, TPO made stem cell production go into overdrive. However, the expanded population of stem cells has a higher proportion of quiescent cells, those in a resting stage in the cell cycle. Quiescent stem cells, said Dr. Tong, are more likely to succeed in a recipient when they are used in bone marrow transplantation. Researchers could build on this knowledge to manipulate HSCs for more effective bone marrow transplants for cancer patients after high-dose chemotherapy or radiotherapy.



African scientists reveal origins of maize virus

African scientists have uncovered how one of the world’s most economically devastating crop diseases emerged, and hope to genetically engineer disease resistant crops using the information. Researchers from the University of Cape Town (UCT), South Africa, compared the genetic sequence of the virulent maize streak virus (MSV) with ten less harmful strains of the virus from across the continent, which infect other grass food crops such as wheat and oats.

“We found that two relatively mild grass viruses had merged through genetic recombination,” said UCT researcher Dr. Arvind Varsani. This merger resulted in an ancestral MSV far more potent than its parents, which moved into maize before spreading rapidly across the continent. The researchers think that this occurred approximately a century ago, just when commercial agriculture was replacing subsistence farming and maize started to overshadow indigenous crops in Africa. “Our results mean that DNA viruses are evolving faster than was thought. This rapid mutation increases the possibility of new plant viruses emerging,” said Dr. Varsani.


Key discovered to cold tolerance in maize

Maize (corn) – the world’s number one feed grain and a staple food for many – does not tolerate cold well. If maize’s intolerance of low temperatures could be overcome, then the length of the growing season and yield could be increased at present sites of cultivation and its range extended into colder regions. Researchers from the Department of Crop Sciences and the Institute of Genomic Biology at the University of Illinois, the United States, may have made a breakthrough on this front.

Plants can be divided into two groups based on their strategy for harvesting light energy: C4 and C3. The C4 groups include many of the most agriculturally productive plants known, such as maize, sorghum and sugar cane. All other major crops, including wheat and rice, are C3. The C4 plants differ from the C3s by the addition of four extra chemical steps, which make these plants more efficient in converting sunlight energy into plant matter. Until recently, the higher productivity achieved by C4 species was thought to be possible only in warm environments. Recently a wild C4 grass related to maize, Miscanthus x giganteus, has been found to be highly productive in cold climates. The Illinois researchers set about trying to discover the basis of this difference, focusing on the four extra chemical reactions that separate C4 from C3 plants.

Each of the four reactions is catalysed by a protein or enzyme. The enzyme for one of these steps, Pyruvate Phosphate Dikinase (PPDK) is made up of two parts. At low temperature, these parts have been observed to fall apart, differing from the other three C4-specific enzymes. The researchers examined the DNA sequence of the gene coding for this enzyme in both plants, but could find no difference, nor could they see any difference in the behaviour of the enzyme in the test tube. However, they noticed that when maize leaves were placed in the cold, PPDK slowly disappeared in parallel with the decline in the ability of the leaves to take up carbon dioxide in photosynthesis. When Miscanthus leaves were placed in the cold, they made more PPDK and as they did so, the leaves became able to maintain photosynthesis in the cold conditions.
The researchers cloned the gene for PPDK from both maize and Miscanthus into a bacterium, enabling the isolation of large quantities of this enzyme. They discovered that, as the enzyme was concentrated, it became resistant to cold, thus the difference between the two plants was not the structure of the protein components but rather the amount of protein present. The findings suggest that modifying maize to synthesize more PPDK during cold weather could allow it to be cultivated in colder climates and be productive for more months of the year in its current locations.


Mapping first plant-parasitic nematode genome sequence

The annotated genome of one of the most destructive nematodes – Meloidogyne incognita, the southern root-knot nematode – has been released recently, with contribution from researchers at Iowa State University, the United States. Sequencing the genome is a very critical step towards comprehensively understanding how the organism works and may pave the way for research on methods to fight the pest. “This is considered to be one of, if not the most important, plant-parasitic nematode species across the world,” said Prof. Thomas Baum, Chair of plant pathology and the Head of Iowa State University’s contribution to the genome sequence project.

Besides being a devastating crop pathogen, M. incognita has some remarkable biological adaptations that make it a very fascinating organism to study. With this sequencing done, Prof. Baum thinks researchers can now try to understand this nematode. He also cautions that finding ways to control this pest will be a long process.

Technology for controlling nematodes has advanced little in the past three decades. Chemical treatments for killing nematodes, called nematicides, are harmful to humans and other animals, and hence they have been restricted in use for decades. Because the root-knot nematode is so widespread, many nematologists around the world were eager to help with the work. The project had the collaboration of researchers from the Insitut National de Recherche Agronomiquea, France, and North Carolina State University, the United States, besides researchers from Belgium, The Netherlands, United Kingdom and Switzerland.



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