VATIS Update Biotechnology . Nov-Dec 2009

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Biotechnology Nov-Dec 2009

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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Proposal to sequence genomes of 10,000 vertebrates

An international group of scientists is proposing to generate whole genome sequences for 10,000 vertebrate species using technology that is yet to be invented! The scientists say new genome sequencing protocols, which will allow them to embark on the project, are close to completion and may be available within a year or two. In preparation, they are identifying collaborators who can help assemble a collection of frozen or otherwise suitably preserved tissues or DNA samples from these species.

The idea behind the Genome 10K proposal is to prepare for the third generation of DNA sequencing technology that began with the Humane Genome Project, according to Dr. Scott Baker, from Oregon State University (OSU) in the United States, who edits the Journal of Heredity that will publish the proposal. Whereas that took nearly 10 years at a cost of more than US$3 billion, the goal now is to sequence an entire genome in less than a week, for a cost of less than US$1,000, he said.

Dr. Baker, Associate Director of OSUs Marine Mammal Institute, is one of the more than 50 scientists worldwide who are collaborating on the proposal. He is coordinating the effort to assemble DNA samples for all known species of cetaceans whales, dolphins and porpoises a task made more difficult because the exact number of species keeps changing. As DNA analysis becomes more sophisticated, molecular differences are emerging among some animals thought to belong to the same species.

Another challenge is to obtain samples for rare, endangered and even extinct species, Dr. Baker said. Further, the variety of species identified will present different challenges for genome sequencing. Dr. Baker and his colleagues have been working for two decades on creating DNA barcodes for different cetacean species. The ability to create entire genome sequences would be greatly benefit conservation and basic scientific understanding of species.

Ribosomes show their medical importance

Dr. Venkatraman Ramakrishnan, awarded this years Nobel Prize for Chemistry for his work on ribosomes, said recently that his work has established the medical importance of ribosomes and praised the Laboratory of Molecular Biology of the Medical Research Council (MRC), the United Kingdom, and the University of Utah, the United States, for supporting his work. He won the Nobel along with Dr. Thomas A. Steitz, the United States, and Dr. Ada E. Yonath, Israel, for studies of the structure and function of the ribosome, an element that translates information contained in the DNA code into life.

MRC said Dr. Ramakrishnans research could lead to the development of better drugs to fight against extreme forms of tuberculosis a disease that kills nearly 1.8 million people every year. Dr. Ramakrishnans basic research on the arrangement of atoms in the ribosome could help scientists to design antibiotics to treat people infected with a bacterium that has developed antibiotic resistance, such as some of the strains of bacteria that cause tuberculosis. Better targeting of the bacterial ribosome should also help to avoid negative effects on human cells thereby reducing the side effects of taking antibiotics, MRC said in a statement.

Bt brinjal, the first GM food crop to gain approval in India

The Genetic Engineering Approval Committee (GEAC) of Indias Ministry of Environment and Forests has given environmental clearance to Bt brinjal (eggplant or aubergine), the first genetically modified (GM) food crop to be allowed in the country for mass cultivation. The crop now awaits government clearance. If approved by the government, Bt brinjal would become the second crop to be commercially cultivated in the country after Bt cotton, which was approved in 2002. The Minister of State for Environment and Forests, Mr. Jairam Ramesh, said the review committees recommendations would be carefully studied before a final decision is taken by the Ministry.

Greenpeace India and other environmental groups had been campaigning against the commercial sale of GM food, and had questioned the bio-safety of such products. The groups had warned the government against taking a hasty decision, citing the need for extensive testing. They also said there was no need of a GM brinjal, as India has a large variety of the indigenously developed vegetable. Brinjal is an important cash crop for more than 1.4 million small and marginal farmers in the country.

The problem in India is compounded with the regulators not enforcing labelling law, which leaves consumers without informed choice with the result that most of them remain ignorant of the fact that they may be buying a GM product. Mahyco, one of the companies seeking approval to sell the Bt technology to local farmers, claims that farmers cultivating brinjal have been suffering due to crop diseases like brinjal fruit and shoot borer (BFSB), which ruins their harvest.
Source: www.

Malaria vaccine trial in Africa hits Phase III

The first-ever Phase III trial for a malaria vaccine has officially begun, with more than 5,000 African children already given the first round of malaria vaccine candidate RTS,S, researchers announced at a recent pan-African conference on malaria in Nairobi, Kenya. It is a really historical moment, said Dr. Joe Cohen, Vice President of R&D for Vaccines for Emerging Diseases & HIV at GlaxoSmithKline (GSK) Biologicals and the co-inventor of the vaccine. While the efficacy of RTS,S leaves plenty of room for improvement as it provides only about a 50 per cent reduction in malaria it is the first vaccine candidate for malaria to warrant a Phase III trial.

In Phase II trials, the RTS,S vaccine showed a 53 per cent reduction in clinical malaria episodes for eight months in children 5-17 months old last year. This August, a trial in Mozambique of kids aged 1 to 4 years suggested that the vaccine is able to provide protection for up to 45 months, but at a lower efficacy. The current trial in seven African countries aims to enrol up to 16,000 children in two target age groups: 5 to 17 months and 6 to 12 weeks. The enrolment for the first group is already 5,000 subjects strong, and the enrolment of the younger age group is expected to begin in the next couple of weeks, Dr. Cohen said. If all goes as planned, the first set of data could be ready to submit for regulatory review in 2012.

RTS,S is the leading vaccine candidate in a global effort coordinated by the PATH Malaria Vaccine Initiative (MVI). It specifically targets Plasmodium falciparum, the malaria parasite that causes the overwhelming majority of cases of the disease in Africa. Dr. Ashley Birkett, MVIs Director of Pre-clinical Research and Development, said the organizations long-term goal is a vaccine that is at least 80 per cent effective for at least four years. MVI also aims to develop vaccines against P. vivax, a less severe but more widespread malaria parasite, as well as vaccines that block the transmission of malaria to interrupt the life cycle of the parasite.

Funding to unlock secrets of immunity and infection

Research into immunity and infection has been given a multi-million pound boost with a major award from the Biotechnology and Biological Sciences Research Council (BBSRC) to scientists at Cardiff University in the United Kingdom. An internationally recognized team from the School of Medicine, led by Prof. Andy Sewell, will further their world-leading work into T-cells after being awarded 3 million by BBSRC.

The funding will allow Prof. Sewell and his team to examine how individual T-cells recognize huge numbers of foreign antigens (known as cross-reactivity). This cross-reactivity is enabled because the receptor molecule on the T-cell surface is highly promiscuous, and it can recognize many similar molecular shapes. While T-cell receptor promiscuity allows T-cells to control infection, it is also thought to be responsible for the harmful effects that these cells can sometimes cause. Autoimmunity is believed to arise when a receptor that is raised to fight infection is inadvertently promiscuous enough to recognize our own tissues. This promiscuous receptor recognition can also result in allergic reactions and is responsible for bodys immune cells attacking a foreign organ in the first week after it is transplanted. T-cell receptor promiscuity sits at the very heart of most human health. Despite its obvious importance, there has never yet been a proper attempt to examine or assess this promiscuity and the T-cell cross-reactivity it enables. New tools developed by the Cardiff team have finally provided the keys to unlock this study and make this research especially timely, said Prof. Sewell, explaining the need for the research.

Plant biotechnology to receive more support

In Germany, a coalition agreement presented by the new government advocates responsible use of plant biotechnology. Key aspects of the agreement between the Christian Democratic Union (CDU), Christian Social Union (CSU) and Free Democratic Party (FDP) are an endorsement of the cultivation of genetically modified (GM) Amflora starch potatoes, regionally determined minimum distances between fields with GM crops and fields with conventional crops, and positive GM-free labelling at European level. As far as the German cultivation ban on Monsantos MON810 maize is concerned, the coalition intends to await the outcome of the ongoing court case.

The agreement emphasises the coalitions aim to achieve a stronger scientific orientation and more efficient European Union (EU) approval procedures for GM organisms in future. However, it does not state a position on the issue of field trials with GM plants. A large number of biosafety research projects are conducted in the field in order to assess potential effects of GM plants under realistic conditions. However, the Bavarian Environment Minister, Mr. Markus Sder of CSU, spoke out against field trials using GM plants, claiming that the risks to the environment and population were simply too great. The coalition partners want to change the Genetic Engineering Act to allow the federal states to set their own minimum separation distances between fields with GM plants and fields with organic or conventional crops.

The reaction of groups and associations to the agreements has been mixed. Germanys organic food industry association (BLW) has severely criticised the agreements on plant biotechnology contained in the coalition agreement, saying it was unbelievable that a specific product from one company was mentioned in the agreement (GM Amflora potato). Greenpeace sees the agreement as evidence that the interests of corporations clearly come before protection of the environment and people. But, the German Raiffeisen Association, an umbrella organization representing the interests of cooperatives in the German food and agriculture sector, welcomed the agreement for its potential to promote plant biotechnology as an industry of the future.

Joint research projects on HIV/AIDS show encouraging results

In India, collaboration between the Department of Biotechnology (DBT) and the Indian Council for Medical Research (ICMR) to promote research on the areas of human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) and microbicides have produced some encouraging leads towards the ultimate goal of developing drugs and antibodies for HIV/AIDS. As many as 18 programmes are at present operational, involving scientists from academic and research centres to design HIV antigens, antibodies, drugs and microbicides. Most of these studies, which are under DBT-ICMR collaborative programme launched in 2007, have shown encouraging results, according to DBT sources.

A total of 15 HIV-1 strains and their co-receptor usages have been identified and isolated to carry out neutralization epitope mapping in HIV-1 envelope of Indian origin. It was observed that serum of a chronically infected antiretroviral therapy-nave patient conferred broad neutralization of diverse heterologous envelopes, a DBT official explained.

A study has been initiated to determine genetic variations in the AIDS-modifying genes and compare genetic differences, correlation with rival load, circulatory chemokines and AIDS progression in infected individuals. A novel luciferase-based simple and quick assay system has been developed for evaluating the inhibitory potential of anti-Tat agents and drugs that interfere directly with interactions, the official revealed. In one of the studies, human mannose receptor (hMR) was found localized on human sperm and vaginal epithelial cells, indicating the possible association of hMR with risk of sexual transmission of HIV, he added.


Sinovac cleared to distribute swine flu vaccine in Mexico

Sinovac Biotech, a developer and provider of vaccines based in China, has received a certificate of approval from Mexicos Secretaria de Salud to supply to the country PANFLU.1, Sinovacs H1N1 pandemic influenza (swine flu) vaccine. The certificate is valid until 13 October 2014. Laboratorios Imperiales S.A. de C.V., a biopharmaceutical company operating in Mexico since 1935, is the exclusive distributor of Sinovacs vaccine products in the Mexican market, pursuant to a prior distribution agreement signed in 2005 with its affiliate. PANFLU.1 is the first China-developed vaccine approved for human use in Mexico and the first H1N1 vaccine to be registered in Mexico.

Probiodrug gets funding for novel Alzheimers programme

In one of Europes largest venture capital investment in biotechnology, Germanys Probiodrug AG took in more than 36 million in a Series B round to finance a new class of Alzheimers disease drugs, based on inhibiting glutaminyl cyclase (QC). The company will also allocate part of the proceeds to developing compounds acting on the same target for treating inflammatory indications. Taking an integrated approach to drug development, Probiodrug is bringing forward a series of candidate compounds at staggered intervals of 9-12 months. The first QC inhibitor is expected to reach the clinic within the coming 24-30 months.

The companys Alzheimers programme is based on an alternative pathological view of the condition. Instead of focusing on disrupting the formation of amyloid beta (Abeta) peptide and its aggregation and deposition into the plaques considered the key pathological hallmark of the disease Probiodrug is focused on pyroglutamate (pE)-modified Abeta, the formation of which is catalysed by QC. Targeting QC has been challenging, as specificity is an obvious requirement to avoid off-target effects, making the medicinal chemistry highly sophisticated.

The funding round was co-led by BB Biotech AG, Switzerland, and Edmond de Rothschild Investment Partners, France. Other new investors were Life Sciences Partners, the Netherlands, and Biogen Idec New Ventures, the United States. Existing investors also participated.
Source: www.

Biocon, Amylin to jointly develop diabetes drug

Indian biotech major Biocon and the United States-based Amylin Pharmaceuticals have entered into an exclusive agreement to jointly develop, commercialize and manufacture a peptide therapeutic for the potential treatment of diabetes. Amylin and Biocon will collaborate to develop the therapeutic potential of the compound and share development costs. The research will centre on Amylins phybrid, a peptide hybrid molecule that combines the pharmacological effects of two peptide hormones. Under the terms of the agreement, Amylin will provide expertise in peptide hormone development, particularly in the area of phybrid technology, and metabolic disease therapeutics. Biocon will utilize its expertise in recombinant microbial expression to manufacture the compound, and leverage its experience in pre-clinical and clinical development of diabetes products.

Monsanto opens first biotech research centre in China

Monsanto Company, the United States-based agri-business giant, is opening its first research centre in China, further demonstrating its commitment to forming technology collaborations in that country. The Monsanto Biotechnology Research Centre in Zhongguancun, Beijing, will strengthen the companys ties with Chinese research institutions in plant biotechnology and genomics.

The new research centre is an extension of the companys commitment to doubling yields in its core crops by 2030 compared to a base year of 2000, while reducing the amount of inputs needed per unit produced by a third. Monsanto currently invests more than US$2 million a day in research to meet this commitment to global agriculture. The Beijing research centre will participate in early stage bioinformatics and genomics research, and serve as a base for collaborations with Chinese scientists. Recently, Monsanto had announced a collaboration with Chinas Huazhong Agricultural University to further gene discovery and develop novel biotechnology traits. Monsanto also has research centres in the United States, Brazil and India.

Syngenta Ventures invests in Metabolon

Syngenta Ventures has made an equity investment in the United States-based biotech company Metabolon, which is focused on the use of metabolomics in research and diagnostics. This is the first direct investment by Syngenta Ventures, the venture capital arm of Syngenta, one of the worlds leading multinational agribusiness companies.

Metabolomics provides mechanistic insight and biochemical markers for complex biological processes. This technology aims to accelerate the development of plants with innovative new native and genetically modified traits. Syngenta Ventures will take a seat on the Board of Metabolon. Financial details of the equity investment were not disclosed.

Clinical Genomics continues joint research with CSIRO

n Australia, Clinical Genomics and the Commonwealth Scientific & Industrial Research Organization (CSIRO) have entered a new phase in their collaboration to develop improved diagnostics for cancers of the colon and rectum (bowel cancer). In an earlier research programme, researchers from Clinical Genomics and CSIROs Preventative Health Flagship used advanced genomics and mathematics to identify a number of biomarker genes capable of differentiating between bowel cancer tissue, even at its very early stages, and normal bowel tissue. They have filed jointly owned patents based on these discoveries. The challenge now is to identify which of these biomarkers can be found in clinical samples, such as blood or stool, with the accuracy to improve diagnosis of bowel cancer. The new collaboration will address this challenge with a particular emphasis on biomarkers for the early treatable stages of disease.

CSIRO has developed a suite of molecular technologies that improve detection of DNA methylation, a chemical change to the structure of DNA associated with some candidate biomarker genes. Along with Clinical Genomics, it will now employ these proprietary technologies to develop a clinical test aimed at testing patient blood and stool for the early detection of bowel cancer. If the effort is successful, these assays will be commercially developed and delivered by Clinical Genomics.

GlaxoSmithKline sees orders for swine flu vaccine soar

GlaxoSmithKline (GSK), United Kingdoms largest pharmaceutical company, has disclosed a big boost in orders for its swine flu vaccine, as governments around the world build stockpiles ahead of the winter. GSK revealed that the number of orders for its H1N1 vaccine had jumped by 50 per cent to more than 400 million since August 2009, putting the company on course for a windfall worth about 3 billion by the end of the year. GSK has received 22 government contracts since the summer, with order for 440 million doses. It manufactures the vaccine in Dresden (Germany) and Quebec (Canada), but the demand is so great about 60 per cent higher than for usual seasonal vaccines that it is also outsourcing production to third-party manufacturers.

The vaccine has been approved by European officials and the United States is expected to follow suit soon. GSK said talks were under way with governments around the world over further supplies. Authorities are also stockpiling large supplies of GSKs anti-viral treatment Relenza, which can relieve swine flu symptoms, providing another lift for revenue. GSK has unveiled plans to expand in China by establishing a joint venture with a local biotech company to produce MMR vaccines ahead of a major expansion in the Chinese public vaccine market. The move is part of a plan to diversify further into the emerging economies of Asia and Latin America. Under the Chinese deal, GSK will build a manufacturing facility, passing on its technology to enable local production within a few years. Initially, about 65 per cent of the venture will be controlled by GSK.


Yeast genomes reveal clues to boost bioethanol production

Two studies published online recently in Genome Research have analysed the genome structures of bioethanol-producing yeasts, uncovering genetic clues that will be critical in developing new technologies needed to implement production on a global scale. The two joint studies, both by researchers from Brazil and the United States, take a major step towards this goal, identifying genomic properties of industrial fuel yeasts that likely gave rise to more robust strains.

In one of the studies, Dr. Lucas Argueso from Duke University Medical Centre, the United States, and co-researchers have sequenced and analysed the structure of the entire genome of strain PE-2, a prominent industrial strain in Brazil. The groups work revealed that portions of the genome are plastic compared with other yeast strains, specifically the peripheral regions of chromosomes, where several sequence rearrangements were observed. These chromosomal rearrangements amplified genes involved in stress tolerance, helping the strain adapt to the industrial environment. As PE-2 is amenable to genetic engineering, the authors believe that their work on PE-2 will open the door to development of new technologies to boost bioethanol production.

Dr. Boris U. Stambuk from Stanford University, the United States, and his colleagues studied the genome structure of industrial bioethanol yeasts, searching for variations in the number of gene copies in five strains used in Brazil, including PE-2. They found that all five industrial strains have amplifications of genes involved in the synthesis of vitamins B6 and B1 compounds critical for efficient growth and utilization of sugar. The group demonstrated that the gene amplifications confer robust growth in industrial conditions, indicating that these yeasts likely adapted to limited availability of vitamins in the industrial process to gain a competitive advantage. The authors suggest that this knowledge can be utilized to engineer new strains of yeast capable of even more efficient bioethanol production, from a wider range of agricultural stocks.

New cancer gene discovered

A new cancer gene has been discovered by a research group at the Sahlgrenska Academy, Sweden. The gene causes an insidious form of glandular cancer adenoid cystic carcinoma usually in the head and neck, and in women in the breast also. The researchers showed that the gene is found in 100 per cent of these tumours, which could lead to quicker and better diagnosis and more effective treatment.

The newly discovered cancer gene is what is called a fusion gene, created when two healthy genes join as a result of a chromosome change. One of the two genes that form the fusion gene is known as MYB. Among other things, this gene controls cell growth and makes sure that the body gets rid of cells that are no longer needed. MYB has long been known as a highly potent cancer gene in animals. However, there was no evidence of the gene being involved in the development of tumours in humans.

Previously it was thought that fusion genes pretty much only caused leukaemia, but our group can now show that this type of cancer gene is also common in glandular cancer, says Prof. Gran Stenman, who heads the research group at the Lundberg Laboratory for Cancer Research at the Sahlgrenska Academy.

The research group also looked at the mechanism behind the transformation of the normal MYB gene into a cancer gene. Genes can be compared to blueprints for proteins. Carefully controlled regulating systems then determine when and how much of each protein is formed. One such regulating system is microRNA, which can turn genes on and off. When this cancer gene forms, this important control system is put out of action, leading to activation of the gene and massive overproduction of an abnormal MYB protein with carcinogenic properties.

Genomes of two E. coli strains sequenced

An international team of researchers from the United States, Republic of Korea and France has sequenced and analysed the genomes of two important laboratory strains of Escherichia coli bacteria. The benign strains K-12 and B, the two most important laboratory types, have been indispensable tools for biomedical and biotechnology research. The genome sequence of K-12, isolated in 1922 in the United States, has been known since 1997. Strain B was isolated in 1918 in France, as the current study discovered. The genomes of the two B strains were sequenced at the Korea Research Institute of Bioscience and Biotechnology and at Genoscope, the French centre for genome sequencing. The two B genomes each contain, like K-12, about 4.6 million nucleotide base pairs (Ts linked with As or Gs linked with Cs).

The new developments allow complete genomes of these two laboratory workhorses to be compared for the first time. Although the B and K-12 strains came into the laboratory half a world apart, their genome sequences show that they are closely related, said Dr. William Studier, a biophysicist at the Brookhaven National Laboratory (BNL) of the United States Department of Energy. The scientists found that B and K-12 genomes have non-random distribution of single base-pair differences between them.

The genome comparisons also turned up some interesting differences between the two B strains. The two B strains REL606 and BL21(DE3) have had separate laboratory histories since 1959. Apparently, as scientists at different labs shared strains for their research, one sample got mislabelled. The current detailed genomic analysis uncovered this long-buried mix-up. With this mystery solved, every difference between the two B genome sequences could be understood in terms of the different laboratory manipulations used on the ancestral strains, Dr. Studier said. This information provided new insights into the types of changes to the genome caused by standard laboratory treatments, including exposure to chemicals, irradiation with ultraviolet light and DNA transfer between genomes.

Scientists identify genetic marker for intelligence

At Trinity College Dublin (TCD), Republic of Ireland, scientists have identified one of the first genetic indicators of intelligence. People who carry the genetic variant within a gene called NOS1 recorded lower IQ scores than those who do not carry the variant. The same test was also carried out among patients with schizophrenia and yielded the same result. Significant differences were also found in the working memory of those who carried the genetic variation and those who did not.

Dr. Gary Donohoe, a TCD clinical psychologist, said the genetic variant they have discovered is significant because it has been so difficult to make the connection between an individuals genetic make-up and their intelligence. In all, 600 people in Ireland and 1,700 in Germany participated in the study. It is hoped that the research will help better understand the nature of intelligence and mental health disorders such as schizophrenia.

A new dimension for genome studies

A new study in the United States from scientists at MIT, the Broad Institute of MIT and Harvard, University of Massachusetts Medical School and Harvard University reveals the 3-D structure of the human genome and answers the thorny question of how each of our cells stows some three billion base pairs of DNA. The work, reported in Science, may also explain how cells control which stretches of DNA are transcribed and which remain silent. Furthermore, the new technique could allow researchers to study how gene expression changes. The new structural data reveal that the human genome is organized into two separate compartments, keeping active genes accessible while sequestering unused DNA in a denser storage compartment. Each chromosome alternates between regions of active, gene-rich DNA and inactive, gene-poor stretches.

The scientists established that the genome adopts an unusual organization known in mathematics as a fractal. This architecture, called a fractal globule, enables the cell to pack DNA incredibly tightly while avoiding the knots and tangles that might interfere with the cells ability to read its own genome. The DNA can easily unfold and refold during gene activation, gene repression and cell replication. Key to deciphering the structure of genome was the development of the new Hi-C technique, which permits genome-wide analysis of the proximity of individual genes.


Inhibitor of heat shock protein is a potential anticancer drug

Scientists have long studied how Heat shock proteins (HSPs), which allow cells to survive stress-induced damage, work in order to harness their therapeutic potential. In the United States, geneticists Dr. Donna George and Dr. Julie Leu from the University of Pennsylvania School of Medicine, have identified a small molecule that inhibits the heat shock protein HSP70. They also showed that the HSP inhibitor could stop tumour formation and significantly extend survival of mice. The research was in collaboration with the lab of Dr. Maureen Murphy at Fox Chase Cancer Centre.

HSP70 is an intracellular quality control officer, refolding misfolded proteins and preventing protein aggregation, which among other disorders, is associated with neurodegenerative diseases. HSP70 also ferries proteins to their proper intracellular locations. Tumour cells, which face a lot of cellular stresses, overexpress HSP70, making it a potentially interesting anticancer target.

The cancer microenvironment exposes malignant cells to a variety of stressful conditions that promote protein misfolding. HSP70 helps cancer cells deal with this stress. Unlike normal cells, which typically express little of HSP70, cancer cells contain high levels of this protein all the time. The inhibitor PES interferes with HSP70 activities that the cancer cell needs to survive. Hence, by targeting HSP70, one can target the cancer cell. The investigators showed that PES interacts with HSP70 by blocking its stress-relieving functions. It also induces HSP70-dependent cell death by disrupting the cells ability to remove damaged components.

A protein that flattens Golgi apparatus

Researchers at the University of California, San Diego, the United States, have pinpointed a protein that keeps the protein transportation hub in the cells going. The protein works in tandem with other molecules to pull membrane packets off the surface of a cells Golgi apparatus, giving the crucial organelle its distinctive flattened shape. It is a nice simple mechanism for how the shape of something is a consequence of its function, says Dr. Seth Field, a co-author of the study.

While the functional details of Golgi apparatus were known, its odd shape has long been a mystery. Researchers have described it as a stack of pancakes: the pancakes are membranes that enclose empty space that proteins travel through. Now Dr. Field and his colleagues have identified the protein responsible for that shape. In an analysis of the binding properties of 4,000 fruit-fly proteins, one called GOLPH3 latched onto another molecule that was known to be important to the Golgis function. Further scans found that a motor protein like those found in muscles also piggybacked on GOLPH3. The researchers found that if GOLPH3, the molecule it attached to or the motor protein was removed, the Golgi apparatus structure collapsed. The removal also shut down the Golgis function. The team concluded that the organelles stretchy shape is a side-effect of its job. The motor protein enables GOLPH3 to pull bubbles full of proteins off the Golgi apparatus and send them outside the cell. In the process, the membranes are pulled flat, like rubber bands.

A clearer view of how eye lens proteins are sorted

New research reveals how proteins that are critical for the transparency of the eye lens are sorted properly and localized in membrane bi-layers. The study by Dr. Thomas J. McIntosh from the Duke University Medical Centre, the United States, and his colleagues analyses how interactions between lipid and protein molecules can selectively concentrate proteins in certain regions of the cell membrane.

Cell plasma membranes are made of a thin bi-layer of lipids interspersed with a diverse group of proteins. These lipids and proteins are distributed across the plasma membrane in specific functional microdomains or rafts. Although raft sequestration of many classes of lipids and proteins has been extensively studied, mechanisms for sorting proteins that span the membrane to form channels are not as well understood.

The researchers were interested in examining whether the plasma membrane distribution of the major eye lens channel proteins, connexins and aquaporin, depends on how they are sorted between raft and non-raft microdomains. Using both detergent extraction and confocal microscopy to analyse reconstituted membranes, the scientists discovered that connexins were primarily located in non-raft domains. In contrast, the microdomain location of aquaporin depended on its aggregation status, which was controlled by the protein: lipid ratio in the membrane. Specifically, under conditions where aquaporin molecules are known to cluster together (homo-oligomerize), aquaporin was enriched in non-raft domains. The scientists conclude that protein-lipid interactions, as modified by aquaporin homo-oligomerization, can be a key factor in the sorting of proteins in lens cell membranes.

Hybrid molecules could help treat Alzheimers disease

One of the many mysteries of Alzheimers disease is how protein-like snippets called amyloid-beta (Abeta) peptides, which clump together to form plaques in the brain, may cause cell death, leading to the diseases devastating symptoms of memory loss and other mental difficulties. Researchers from the University of Michigan, the United States, have developed new molecular tools that can help investigate the process by which Abeta forms the telltale clumps. The molecules also hold promise in Alzheimers disease treatment.

Scientists do know that copper and zinc ions are somehow involved not only in the Abeta aggregation process, but apparently also in the resulting injury. They have also found that chelators, molecules that can mop up metal ions, hamper both Abeta clumping and the production of the harmful reactive oxygen species, suggesting that chelators could be useful in treating Alzheimers disease.

However, most known chelators cannot cross the blood-brain barrier, the barricade of cells that separates brain tissue from circulating blood, protecting the brain from harmful substances in the bloodstream. Further, most chelators are not precise enough to target only the metal ions in Abeta; they could grab and disable metals performing vital roles in other biological systems. Dr. Mi Hee Lim and co-workers used a new strategy to develop bi-functional small molecules that not only grab metal ions, but also interact with Abeta. They attached metal binding sites to molecules known for Abeta recognition. In collaboration with Prof. Ayyalusamy Ramamoorthy, they then used NMR spectroscopy to confirm that the new, hybrid molecules still interacted with Abeta.

In experiments in solutions with or without living cells, the researchers demonstrated that the bi-functional molecules were able to regulate copper-induced Abeta aggregation, not only disrupting the formation of clumps, but also breaking up clumps that already had formed. The new molecules performed better than clioquinol, a clinically available metal chelator that showed promise in trials with Alzheimers patients, but has side-effects that limit long-term use.

A protein that enhances long-term memory

What one learns through repeated study tends to be preserved longer in memory if the learning sessions are spaced out between rest intervals. Neuroscientists at Cold Spring Harbour Laboratory (CSHL), the United States, have now discovered how this so-called spacing effect is controlled in the brain at the level of individual molecules. The CSHL team, led by Prof. Yi Zhong, has found in a fruit fly model that a protein called SHP-2 phosphatase controls the spacing effect by determining how long resting intervals between learning sessions need to last so that long-lasting memories can form.

Prof. Zhongs team has shown for the first time that the spacing effect has a genetic and molecular basis. The CSHL team has also found that the duration of the resting intervals can be manipulated for achieving better memory by genetically altering SHP-2 phosphatase. This ability to exploit the spacing effects molecular control to enhance memory could be useful in a wide range of settings, such as education, advertising and, most importantly, in treating learning and memory disorders, says Prof. Zhong.

More than half of those with Noonans Syndrome a genetically inherited learning and memory disorder have mutations in PTP11 gene, which encodes SHP-2 phosphatase. To understand how this change impedes long-term memory, Prof. Zhongs team engineered these mutations into a gene (called corkscrew) in fruit flies that is the functional equivalent of PTP11 in humans. The mutant flies were taught to avoid certain odours through a regimen of repeated learning sessions broken up by resting intervals lasting 15 minutes. But this training regimen, which induces long-term memory in normal flies, failed to work in the mutants because the increased activity of SHP-2 phosphatase disturbed the spacing effect.

Normally, as each learning period ends, SHP-2 phosphatase activity inside stimulated neurons triggers a wave of biochemical signals, which have to peak and decay before the next learning session can begin. The repeated formation and decay of the biochemical signal during each rest interval induces long-term memory. In normal flies, these signal waves took 15 minutes to peak and decay. In the mutants with excess protein activity, however, the signalling wave took 40 minutes to decay. The scientists found that increased production of the protein with normal activity could shorten the duration of the resting interval to 2.5 minutes.

Scar-eating enzyme helps repair spinal damage

A group of scientists in the United States believe that they have solved one of the thorniest issues involved in repairing spinal damage. They created an enzyme chondroitinase ABC that can eat through scar tissue, allowing the injured nerve to repair itself and heal the spine. Starting with the knowledge that an unstable enzyme could do the work, the biomedical engineers at the Georgia Institute of Technology and Emory University set out to engineer a new one. They combined the enzyme with a sugar for stability and then injected it into the spine using tiny straws kept in place with a special gel. That approach worked in the injured spines of rats. The goal is that at the time the surgeon is removing the offending bone, the gel is injected to sit on top of the injury site to prevent new scar from forming, says Dr. Ravi Bellamkonda. This, however, is just one piece of a complex puzzle. To repair damaged spines, the nerve fibre growth has to be stimulated to communicate with the brain.
Source: www.fierce


Enhanced stem cells promote tissue regeneration

Researchers have enhanced stem cells ability to regenerate vascular tissue by equipping them with genes that produce extra growth factors. In a study in lab mice, they found that the stem cells successfully generated blood vessels near the site of an injury, allowing damaged tissue to survive. The new supercharged stem cells could be used to treat an infarction or to induce blood supply for engineered tissues.

After removing stem cells from mouse bone marrow, Dr. Daniel Anderson and colleagues from the Massachusetts Institute of Technology, the United States, used specially developed nanoparticles to deliver the gene for the vascular endothelial growth factor (VEGF). The stem cells were then implanted into damaged tissue areas. The nanoparticles, which scientists have also tested to deliver cancer treatments, are believed to be safer than the viruses often used for gene delivery. The technique needs more improvements before any human trials can begin, according to Dr. Anderson.

Gene therapy repairs injured human donor lungs

Scientists in the McEwen Centre for Regenerative Medicine, University Health Network, Canada, have successfully used gene therapy to repair injured human donor lungs, making them potentially suitable for transplantation into patients. This technique could significantly expand the number of donor lungs by using organs that are currently discarded, and improve transplantation results.

A team of researchers led by Dr. Shaf Keshavjee, Senior Scientist at McEwen Centre and Director of the Lung Transplant Programme, developed a technique of ex vivo gene delivery to donor lungs, before they are implanted into a recipients body. The technique is simple and effective in improving lung function. It is estimated that the number of donor organs available for lung transplants could easily be doubled with this technique.

The researchers first developed a strategy to preserve lungs at normal body temperature, with the lungs kept outside the body in a protective dome. The Toronto XVIVO Lung Perfusion System continuously pumps a solution of oxygen, proteins and nutrients into injured donor lungs, mimicking normal physiological conditions. Then, using a bronchoscope, the scientists injected an engineered adenovirus vector a common cold virus with an added IL-10 gene through the windpipe into the human lungs. The study found that the donor lungs that received the gene therapy, in addition to the ex vivo perfusion, significantly improved their function with regards to blood flow throughout the lungs and their ability to take in fresh oxygen and get rid of carbon dioxide. The boosted IL-10 effect lasts for up to 30 days in the lung.

Scientists visualize how bacteria talk to one another

Using imaging mass spectrometry, researchers at the University of California-San Diego (UCSD), the United States, have developed tools that will enable scientists to visualize how different cell populations of cells communicate. Their study shows how bacteria talk to one another an understanding that may lead to new therapeutic discoveries for diseases ranging from cancer to diabetes and allergies. In the paper published in Nature Chemical Biology, Dr. Pieter C. Dorrestein and colleagues describe an approach they developed to describe how bacteria interface with other bacteria in a laboratory setting. The scientists utilized a technology called natural product Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) imaging mass spectrometry to translate the language of bacteria.

A single bacterial species is capable of producing many bioactive compounds that can alter neighbouring organisms. The approach developed by the UCSD research team enabled them to observe the effects of multiple microbial signals in an interspecies interaction, revealing that chemical conversations between bacteria involve many signals that function simultaneously. Such exchanges by microbes are complex, involving 10, 20 or even 50 molecules at one time. Now scientists can capture that complexity, says Dr. Dorrestein.

Liver cells grown from skin cells to treat liver diseases

Scientists at the Medical College of Wisconsin, the United States, have successfully produced liver cells from patients skin cells, opening the possibility of treating a wide range of diseases that affect liver function.

The Medical College research team, led by Prof. Stephen A. Duncan, generated patient-specific liver cells by first repeating an earlier work at the University of Wisconsin-Madison that showed that skin cells could be reprogrammed to become cells that resemble embryonic stem cells. They then tricked the skin-derived pluripotent stem cells into forming liver cells by mimicking the normal processes through which liver cells are made during embryonic development. At the end of this process, the scientists found that they are able to produce easily large numbers of relatively pure liver cells in laboratory culture dishes. The researchers believe that the reprogrammed skin cells could be used to investigate and potentially treat metabolic liver diseases. The liver may be particularly suitable for stem-cell based therapies because of its remarkable capacity to regenerate.

Scientists halt brain disease with new gene therapy

An international team of scientists have used a disabled form of human immunodeficiency virus (HIV) to deliver working genes to two boys with the rare and fatal brain disease X-linked adrenoleukodystrophy (ALD). Dr. Patrick Aubourg of Inserm-University Paris Descartes, France, who led the study, said it is the first time scientists successfully used an HIV-derived delivery technique for gene therapy in humans, and the first time gene therapy is used effectively in a severe brain disease.

ALD patients gradually lose the myelin sheath, a protective layer coating the brains nerve fibres, leading to blindness, deafness, seizures and progressive dementia. X-linked ALD, the most common form, affects boys from around 6 years old, and they usually die before reaching adolescence. The disease can be halted using bone marrow transplants because the donor marrow includes cells that develop into myelin-producing cells. But finding a matching donor can be difficult and take time, and the transplant is risky.

In their study, Dr. Aubourg and his team took blood stem cells from the patients bone marrow and used the new vector system to alter them genetically by inserting a working copy of the ALD gene. The modified cells were then put back into the patients. Two years later, the scientists could still detect ALD proteins in the patients, but the disease had stopped getting worse.
Source: www.

Lung tissue generated from human embryonic stemcells

Scientists in Belgium have successfully differentiated human embryonic stem cells (hESC) into major cell types of lung epithelial tissue, using a convenient air-liquid interface. The technique could provide an alternative to lung transplants for patients with lung injury due to chronic pulmonary disease and inherited genetic diseases such as cystic fibrosis. Dr. Lindsey Van Haute and colleagues from the Department of Embryology & Genetics at the Free University of Brussels (Vrije Universiteit Brussel) demonstrated that hESC could be converted into epithelial-like cells in human models. They assessed hESC differentiation using an air-liquid interface system that mimics the conditions found in an adult trachea.

Expression data of lung-specific biomarkers from quantitative real-time polymerase chain reaction supported the differentiation into lung epithelial cells. Further, the combination of these mRNA expression results, as well protein expression, secretion and localization showed the presence of the major cell types of lung epithelial tissue. This study shows that hESC can differentiate into lung epithelial-like tissue without specific growth factors or embryoid body formation. The air-liquid interface on a porous membrane combined with low serum is sufficient to prime the cells to form an airway epithelial-like tissue. Dr. Van Haute states that hESC has the capacity to differentiate in vivo and in vitro into cells from all three germ lineages, making them particularly important in developmental biology, regenerative medicine and in vitro pharmacological studies.

Magnetic nanoparticles to diagnose, monitor and treat

The future for magnetic nanoparticles (mNPs) appears very bright. With the design of theranostic molecules, mNPs could play a vital role in developing one-stop tools to simultaneously diagnose, monitor and treat a wide range of common diseases and injuries. Multifunctional particles that are modelled on viral particles, such as the flu and HIV, are being researched and developed to carry signal-generating sub-molecules and drugs, able to reach target areas through a safe sprinkling of tiny mNPs, creating a medical means to confirm specific ailments and automatically release healing drugs while inside a living system.

The magnetic component of the direction-giving nanoparticles is normally ferric oxide, which is coated in a biocompatible surface, sometimes using, for example, fatty acids, to provide stability during the particles journey through ones body. For biomedicine, the particles are useful because they allow the addition of specific signal triggering molecules to identify certain conditions, or dyes to help in medical imaging, or therapeutic agents to remedy a wide-range of afflictions.

As documented, mNPs have sparked interest after being attached to stem cells and used in vivo to remedy heart injury in rats. On humans, Germanys Charit Hospital used a technique, called hyperthermia, that involved mNPs destroying a particularly severe form of brain cancer in 14 patients. The technique, using well-tested knowledge that tumour cells are more sensitive than healthy cells to temperature increases, employs mNPs to direct nano-heaters towards the inoperable tumours and, essentially, cook them to death.


Beneficial effects of nano-agriculture

With potential adverse health and environmental effects often in the news about nanotechnology, scientists in Arkansas, the United States, are reporting that carbon nanotubes (CNTs) could have beneficial effects in agriculture. Their study found that tomato seeds exposed to CNTs germinated faster and grew into larger, heavier seedlings than other seeds. That growth-enhancing effect could be a boon for biomass production for plant-based biofuels and other agricultural products, they suggest.

The study by Ms. Mariya Khodakovskaya and her colleagues note that considerable scientific research is underway to use nanoparticles wisps 1/50,000th the width of a human hair in agriculture. The goals of nano-agriculture include improving the productivity of plants for food, fuel and other uses. The scientists report the first evidence that CNTs penetrate the hard outer coating of seeds. Nanotube-exposed seeds sprouted up to two times faster than control seeds. Further, the seedlings weighed more than twice as much as the untreated plants. Those effects may occur because CNTs penetrate the seed coat and boost water uptake, the researchers state. This observed positive effect of CNTs on the seed germination could have significant economic importance for agriculture, horticulture, and the energy sector, such as for production of biofuels, they add.

Drought-tolerant plant gene discovered

An international group of plant scientists, led by Dr. Gonzalo Estavillo and Prof. Barry Pogson at the Australian National University, Canberra, have discovered a subtle mutation in Arabidopsis plant that may have far-reaching implications for establishing drought resistance across the plant kingdom. We discovered a particular mutant gene called SAL1 that enabled plants to survive longer without added water, and seeing the obvious potential, we began to investigate, said Dr. Estavillo.

One potential the group is currently exploring is the application of the mutation to food crops such as rice or wheat, and the researchers will now begin to introduce the mutant characteristics into the elite wheat cultivars currently used in agriculture industry. The ultimate aim of the project is to develop wheat lines with improved drought tolerance and water use, explained Dr. Estavillo. The next step will be to identify wheat mutant plants lacking SAL1 genes identified by molecular biology procedures. We expect that these mutants should remain green, turgid and photosynthetically active, producing more leaves, flowers and seeds during mild to moderate water deficit.

The SAL1 mutation has the advantage of offering less controversial solutions to the enhancement of food crops. As the basis of the mutation is a missing gene, it would also be potentially possible to create drought-tolerance in a plant like wheat without employing transgenic methods, or what is commonly referred to as genetic modification (GM) technology, which rely on splicing genes into existing genomes. Instead, using traditional plant breeding techniques, drought resistance traits could potentially be introduced through a process of interbreeding, alleviating both public concerns about GM food stock, as well as introducing drought resistance to commercial varieties of the plant as quickly as possible.

Drought-hardy maize ready for field trials

Drought-resistant maize varieties will be making their way from the greenhouse to the field as soon as South African scientists get the regulatory green light. The researchers at the University of Cape Town in South Africa have genetically engineered maize to contain four genes from the desiccation-resistant Xerophyta viscosa plant commonly known as the resurrection plant. The genes give X. viscosa its ability to withstand 95 per cent dehydration.

The X. viscosa genes act as a signal to the maize plant to go into survival mode when it becomes dehydrated, explains Dr. Jennifer Thomson, a microbiologist at the University of Cape Town and leader of the research project funded by The Maize Trust. The modified plant is expected to withstand environmental conditions that currently result in a greatly reduced harvest, such as late rains. She hopes to start field trials, in cooperation with the Department of Agriculture, early in 2010 after negotiating biosafety regulations that control the cultivation of genetically modified organisms in South Africa.

Maize containing an insect-resistance gene is grown in developing countries including the Philippines and South Africa. Drought-resistant maize is being trialled in Asia while maize resistant to maize streak virus is in development. Efforts are also underway to engineer maize with nutritional benefits.

How plants and bacteria `talk to thwart disease

In plants, a receptor molecule pairs up with a specific molecule on the invading bacteria to spur the immune system into action to defend against the invasion of the disease-causing microbe. Unwrapping some of the mystery from how plants and bacteria communicate in this dance of immunity, scientists at the University of California-Davis (UCD), the United States, have identified the bacterial signalling molecule that matches up with a specific receptor in rice plants to ward off a devastating disease known as bacterial blight.

Because similar pairs of receptors and bacterial signalling molecules are known to exist not only in rice but also in other plants, as well as animals and humans, we are hopeful that this work will lead to new strategies for controlling diseases in plants and people, said UCD plant pathologist Dr. Pamela Ronald, who led the research. In 1995, Dr. Ronalds laboratory had identified the XA21 gene, which produces a receptor protein that recognizes Xanthomonas oryzae pv. Oryzae (also known as Xoo), which causes bacterial blight disease. Xoo and other species of Xanthomonas infect virtually every crop species in the world. Subsequent discoveries revealed that receptors with striking structural similarities to the XA21 receptor protein exist in other plants, flies, mice and even humans. These receptors were later named pattern recognition receptors or PRRs because they have the ability to recognize, and launch a protective immune defence against, molecules that occur across species in a large class of disease-causing microbes. In the new study, Dr. Ronald and her colleagues identified a peptide, a compound that they call ax21, as the molecule that binds with the XA21 receptor protein. The binding triggers a defence response against the bacterial disease.

The researchers note that ax21 is also found in many other species of Xanthomonas as well as in Xylella fastidiosa, a microbe that causes the devastating Pierces disease in grapes. Furthermore, ax21 is even found in Stenotrophomonas maltophilia, a bacterium that causes respiratory tract infections in humans.
Source: www.bioscience

Hard winter wheat varieties

The Agricultural Research Service (ARS) of the United States Department of Agriculture (USDA) has released the first hard winter wheat varieties bred and developed for production in the eastern areas of the country. NuEast, a hard red winter wheat, and Appalachian White, a hard white winter wheat, were bred by ARS plant pathologist and geneticist Dr. David Marshall.

Soft winter wheats which are used to make pastries, cookies and biscuits are typically grown in the eastern United States. Hard wheats, which are best suited for making bread, have not been traditionally successful in the eastern states because the areas humidity increases the incidence of disease in the field. This in turn affects yield and the quality of the grain. NuEast addresses these problems. In field tests, NuEast had significantly higher grain yield than the check varieties. It also showed moderate reaction to powdery mildew, but was more resistant than some check varieties. NuEasts resistance to leaf rust is good, and it is moderately resistant to stem rust. Very few hard white wheats are grown in the United States. The main challenge with growing hard white wheat under humid conditions in the east is the pre-harvest sprouting typically associated with white wheats, says Dr. Marshall. Over three years of testing, Appalachian White had much higher yield than the only other variety that could be considered acceptable in the eastern states. Appalachian White also showed a higher level of resistance to powdery mildew, stripe rust, leaf rust and Hessian fly.


Prebiotics and Probiotics Science and Technology

The dietary use of live microorganisms has a long history. Soured milks and cultured dairy products were in use even before the existence of microorganisms was recognized. Food fermentation using microorganisms is one of the oldest methods for producing and preserving food. The aim of this publication is to provide a comprehensive overview on the advances in the field. The two volumes present the science underpinning the probiotic and prebiotic effects, the latest in vivo studies, the technological issues in the development and manufacture of these types of products, and the regulatory issues involved. The publication is so structured as to cover all aspects of the topics in a logical manner, avoiding replication. It would serve as a useful reference for both scientists and technologists working in academic and research institutes, as well as the industry.

Bioinformatics Methods in Clinical Research

In Bioinformatics Methods in Clinical Research, experts examine the latest developments impacting clinical omics, and describe in great detail the algorithms that are currently used in publicly available software tools. They discuss statistics, algorithms, automated data retrieval methods, as well as experimental consideration in genomics, transcriptomics, proteomics and metabolomics. Composed in the highly successful Methods in Molecular Biology series format, each chapter contains a brief introduction, provides practical examples on methods, results, and conclusions from data mining strategies wherever possible, and includes a Notes section which shares tips on troubleshooting and avoiding known pitfalls.

For the above two publication, contact: Customer Service Centre, Springer GmbH, Haberstrasse 7, 69126 Heidelberg, Germany. Tel: +49 (6221) 345 4301; Fax + 49 (6221) 345 4229; E-mail:


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