VATIS Update Biotechnology . May-Jun 2009

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Biotechnology May-Jun 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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China looks to expand stake in stem cell technology

China will build Asias biggest base to develop uses for stem cell medical technology, which Mr. Chen Zhu, the countrys health minister, described as having huge potential for development. Chinas base will be in Taizhou, an area of Jiangsu with many medical and pharmaceutical businesses, and will cover 20,000 square metres and include a clinic, it is reported.

Stem cell techniques use the bodys master cells to create new cells that medical researchers hope can be used to fight diseases and heal injuries. Mr. Zhu said his country could become a leader in finding uses for the technology.

The stem cell and regenerative medicine sector is one of Chinas new high-tech biological sectors with the strongest development potential, Chen said in a message marking the launch of the project in eastern Jiangsu province. China is looking to expand its stake in this increasingly competitive area, where it has few of the regulatory controls and controversies that have constrained research elsewhere, he added.

Saudi Arabia sets up nanotechnology facility

Saudi Arabia is aiming to open an international research centre dedicated to nano-manufacturing. The Centre of Excellence in Nano-manufacturing Applications (CENA) is a joint venture between the King Abdulaziz City of Science & Technology (KACST) and technology giant, Intel Corporation. The centre will be based in KACST at Riyadh, the Saudi capital, and is expected to open in 2010.

KACST will provide funds for equipment, while Intel will steer research and provide expert guidance for students. In a move to tackle the brain drain in the Middle East, graduate students from the region would get CENA sponsorships.

Mr. Mohammed Kuchari, associate professor at King Abdul Aziz University, says that CENA will join a number of other new nanotechnology facilities in Saudi Arabia several research centres and the countrys first private company. It will complete the golden triangle for harnessing the combined power of education, research and private investment, he adds.

Grant from the United Kingdom for agri-biotech research

The Indian Institute of Science, Leeds University of the United Kingdom and the Indian Agriculture Research Institute have together received a 1 million grant from the United Kingdoms government to research and develop sustainable, anti-parasitic, biotech crops using new bio-technologies.

The research project will aim to conserve the growth and supply of food, control parasites and alleviate the annual global crop loss of about US$ 125 billion. It will also develop new ecological and parasite-resistant crops to bring worldwide agriculture sustainability, particularly in the semi-arid peninsular and western India. Indias Department of science and technology is co-ordinating crop research, which is expected to complete by June 2013.

Researchers from all the three institutions will look at developing technologies that would have great value for farmers in semi-arid peninsular and western India, where climate change is likely to have its largest impact. The research project, which will run for about four years, will also facilitate interaction between India and the United Kingdom in basic science and applied agriculture, translate research into application, as well as bring awareness of agricultural challenges to scientists across the world.

First camel clone born

Scientists in Dubai say they have created the worlds first cloned camel. Injaz, a female one-humped camel, was born on 8 April, after more than five years of work, United Arab Emirates newspapers reported. Scientists say DNA taken from a cell in the ovary of an adult camel was put into an egg from a surrogate mother. Injaz, which means achievement in Arabic, was born after an uncomplicated 378-day gestation period, reports said. The baby camel, weighing 30 kg, has been confirmed as being genetically identical to the camel from which the cells were taken.

New biotechnology and genomic centre for plants

A new Biotechnology and Genomic Centre for Plants (CBGP) has been set up at the Universidad Politcnica de Madrid (UPM), Spain, as a joint undertaking of UPM and Instituto de Investigacin y Tecnologa Agraria y Alimentaria (INIA). It aims to advance research for the improvement of the knowledge related to vegetal field and associated organisms. CBGP will aim to develop research and training fields, such as proteomic and biology systems. It will also focus on the efficiency of vegetal production, a key factor for the future of agriculture.

The investment for this project will come mainly through financial aid from Technology Plant Programme of the Ministry of Science and Innovation (MICINN). As per the agreement signed by UPM and INIA, MICINN will provide half million euros to this Centre every year. Another million euros will be invested to procure equipment and build the infrastructure.

CBGP, which is headed by Professor Fernando Garca-Arenal, will organize its activities in three areas: the biology of vegetal development, interaction of plant micro-organisms, and functional genomic. The research activities will cover differentiation of roots, flowering, seeds development, stoppage of growth and development in winter. These features will be a key factor for the understanding and manipulation of vegetal production because they affect the collection of water and nutrients, fruit production, and grains or wood production. It looks to understand plants adaptation to adverse conditions, such as soil salinity, that are salient for semi-arid climates and defence mechanisms (resistance and tolerance) to pathogenic micro-organisms (bacteria, viruses and fungi).

Demographics drive healthcare delivery market in APAC region

While the economic recession poses great challenges for the global industries to handle, the healthcare delivery market remains as one of the few recession-proof sectors, alongside education and entertainment industries. Growing and ageing population, globalization of medical delivery services, and growing prevalence of chronic diseases have enhanced the necessity of profound healthcare delivery systems globally.

Mr. Keith Lee, a Frost & Sullivan consultant, says that across Asia-Pacific (APAC) region, the healthcare delivery market is driven by the changing demographics, which result in the strong rise of ageing population and chronic diseases. Furthermore, the enhanced quality of healthcare in APAC has provided opportunities for countries like India, Thailand, Malaysia and Singapore to potentially develop as the medical hubs in the region. These prevailing factors growing and ageing population, increasing dominance of chronic disease, popularity of medical tourism, and the improved affordability of quality healthcare through national health insurance programmes in various APAC countries are likely to push APAC healthcare delivery sector beyond the US$570 billion mark by 2012, Mr. Lee says.

Despite the supporting growth factors in APAC healthcare delivery, majority of the developing countries are still faced with the challenges of insufficient funding for the healthcare sector in relation to the national GDP and disparity in terms of distribution of healthcare within the urban and rural regions. Furthermore, the attraction of new players and the expansion of the existing major players will likely intensify the level of competition in both the domestic and regional markets, in which majority of the healthcare providers are expected to compete on the basis of operational efficiencies and brand name leveraging, adds Mr. Lee.


IBPL to make large investment for MAbs facility

Intas Biopharmaceuticals (IBPL), an Indian biotechnology company, has signed a Memorandum of Understanding with the Gujarat government for setting up a separate manufacturing facility for monoclonal antibodies (MAbs), a recombinant mammalian platform product. IBPL will invest Rs 1.6 billion for setting up a new manufacturing facility at Sanand near Ahmedabad. It is expecting commercial activity at the new facility to start from 2011, and expand in a phase-wise manner.

IBPL will screen technologies, new molecules and identify the most promising ones, prioritising them on the basis of their business potential and compatibility. It has acquired 23,000 square metres of land and has initiated the engineering design phase for the project. The facility dedicated for MAbs, will undertake large-scale manufacturing with a capacity of 5,000 litres in phases.

BPL is planning to generate clones for commercial production of protein using state-of-the-art technologies to improve yields, quality as well as adopting novel expression systems with an objective to build intellectual property (IP) over the long run. MAbs has strong potential of generating IP in terms of patents and could provide a novel platform for delivery of many protein therapeutics.

Glaxo and Pfizer create new HIV drug company

Pharmaceutical giants GlaxoSmithKline PLC, based in the United Kingdom, and Pfizer Inc., from the United States, will pool their resources to create a new company to develop and sell HIV medicines, leveraging a minimal investment into a market-leading position. The two companies plan to blend Glaxos portfolio of HIV drugs now on the market some with patents approaching expiration with Pfizers more robust pipeline of drugs in development.

With 11 HIV medicines already on sale, the new venture will have a 19 per cent market share, ranking it second, behind sales leader Gilead Sciences Inc. The combination of a broad current revenue base and a new diverse pool of pipeline assets provides a significant platform to invest in developing and delivering new HIV medicines, said Glaxo CEO Mr. Andrew Witty. The name of the new company, to be based in London, will be announced when the deal closes, now set for the fourth quarter.

Mr. Witty said the R&D operations would remain basically unchanged. The company will have an initial capitalization of about US$373 million, 90 per cent of it from Glaxo, which will initially hold an 85 per cent equity interest in the new company, with Pfizer holding the remaining 15 per cent. As time goes by, Mr. Witty said, those stakes will grow or dwindle according to which company is producing more successful drugs. The new company will have several market-leading therapies, including Combivir, Kivexa and Selzentry. However, it will not include Glaxos vaccine programme, which will continue separately. The new company will have a pipeline of six drugs in human testing, four in mid-stage tests, and 17 experimental compounds. Based on 2008 results, the combined portfolio generates sales of around US$2.4 billion.

Monsanto plans launch of herbicide resistant Bt cotton

The United States-based multinational agri-biotech company Monsanto Holdings Pvt. Ltd. is planning to launch a herbicide-resistant genetically modified (GM) variety of Bt cotton in India, said its Senior General Manager, Public Affairs, Mr. Christofer Samuel. In the new technology, already introduced in cotton varieties available in other parts of the world, a new gene named Roundup Ready Flex would be inserted into the genome of its cottonseed Boll Guard II, which would make the plant resistant to herbicides. Nearly 35 per cent of a farmers input cost goes into physically removing weeds from the cotton growing field, which could be saved by using the new variety, said Mr. Samuel.

The company already has a herbicide named Roundup in the Indian market. Its listed Indian outfit Monsanto India Ltd. produces Boll Guard I and II, two pest-resistant Bt cotton varieties, in a joint venture with Maharashtra Hybrid Seeds Company Ltd. The company is presently undertaking a study on how to customize the seed to Indian conditions and on the farmers receptiveness to the seed, Mr. Samuel said. The seed is expected to hit Indian markets within five to six years, he said, adding that the company was also open to launching a GM sugarcane it recently launched globally.

GVK Bio ties up with Chinese firm for clinical trials

India-based integrated research services provider GVK Biosciences (GVK Bio) and Excel PharmaStudies (Excel), a clinical research organization from China, have entered into a strategic alliance to conduct clinical trials in Asia. The alliance provides clinical trial sponsors access to the talent pool, scientific skills, flexible resourcing and cost-effectiveness of both India and China, says a press release from GVK Bio.

Under the terms of the arrangement, GVK Bio and Excel will help sponsors conduct and manage Phase II-IV clinical trials, statistical analysis and medical writing. Any India trial for Excel will be carried out by the GVK Bio clinical research team and will be managed by a core project management team of Excel. Similarly, a GVK Bio China trial will be carried out by the Excel team and managed by GVK Bios project management team. This is a first of a kind alliance between Indian and Chinese contract research organizations.

Victoria in global alliance with Dow AgroSciences

Australias Victoria state has forged a global alliance for crop innovation with Dow AgroSciences LLC, based in the United States, Minister for Innovation of Victoria Mr. Gavin Jennings announced recently. The research partnership will see Victoria strengthen its position as a leader in agricultural biotechnology, as scientists in Australia and the United States work together to develop new plant traits and plant varieties for Victorian and international farmers.

The agreement which established a significant collaborative R&D effort between the Victorian Department of Primary Industries (DPI) and Dow AgroSciences LLC is the largest international agricultural biotechnology alliance undertaken by the Victorian government to date. The initial research projects will focus on the development of agronomically important technologies that will improve yields in crops to meet growing global demands for food, feed and energy, said Prof. German Spangenberg, DPIs Executive Director of Biosciences Research who is to lead the R&D efforts in Victoria.

The key crops will include canola, which is the third largest crop in Australia, and will further enhance Dow AgroSciences Omega-9 canola oil platform. Other crops targeted include maize and wheat (for traits) and bioenergy crops. The new Biosciences Research Centre, a joint venture between the Victorian government and La Trobe University, will boost Victorias ability to make these important scientific discoveries. The facility, to be located in Melbourne, will be a world-class centre for agricultural biosciences research and development.

Amorfix and BioMosaics join hands to develop cancer test

Amorfix Life Sciences Ltd., Canada, and BioMosaics Inc., the United States, have announced a collaboration to develop and commercialize a blood-based assay for early detection of hepatocellular carcinoma (HCC) or primary liver cancer. The collaboration incorporates existing technology for the blood test licensed to BioMosaics, plus new material from Sunnybrook Research Institute (SRI), Canada, needed to improve the test, to be used by Amorfix for assay development. On successful development, the product will be commercialized by BioMosaics through its existing distribution network.

The new test is based on antibodies to the biomarker Glypican-3 (GPC3), discovered by Dr. Jorge Filmus at SRI. The collaboration utilizes BioMosaics expertise in the cancer biomarker area and the assay development capability at Amorfix. Antibodies to GPC3 are sold worldwide by BioMosaics for use in pathology laboratories to confirm HCC, and GPC3 is widely accepted as an immunohistochemical biomarker of early HCC detection.


Scientists identify key factors in heart cell creation

Researchers at the Gladstone Institute of Cardiovascular Disease, the United States, have identified for the first time key genetic factors that drive the process of generating new heart cells. The discovery, reported in the journal Nature, provides important new directions on how stem cells may be used to repair damaged hearts.

For decades, scientists were unable to identify a single factor that could turn non-muscle cells into beating heart cells. Using a clever approach, the research team led by Dr. Benoit Bruneau found that a combination of three genes could do the trick. This is the first time any combination of factors has been found to activate cardiac differentiation in mammalian cells or tissues.

Two of the three genes encode for two transcription factors, GATA4 and TBX5, which cause human heart disease when mutated and also co-operate with each other to control other genes. When the scientists added different combinations of transcription factors to mouse cells, these two seemed important for pushing cells into heart cells but they were not enough.

A surprising factor was the cardiac-specific protein BAF60c, which helps determine whether transcription factors like GATA4 and TBX5 can even gain access to the DNA regions they were supposed to turn on or off. Based on their previous observations, Dr. Bruneau and Dr. Takeuchi looked at Baf60c in heart differentiation. The effect was dramatic. Addition of the three factors directed differentiation of mouse mesoderm, which normally has the potential to make bone, blood, muscle, heart and other tissues, specifically into cardiac muscle cells (cardiomyocytes) that beat rhythmically, just like normal heart cells. Even cells that normally contribute to the placenta could be induced to transform into beating cardiomyocytes. Together, these factors give us a potent mechanism to control cellular differentiation, said Dr. Bruneau, and help understand how to reprogramme new cardiomyocytes for therapeutic purposes.

Cattle genome sequencing promises health benefits

The landmark sequencing of the domestic cattle genome, reported in the journal Science, could lead to important new findings about health and nutrition, said a participating researcher from the Michigan State University, the United States. Dr. Theresa Casey, a research assistant professor in the Department of Animal Science, joined 300 colleagues around the world in a six-year project to complete, annotate and analyse the bovine genome sequence.

The species Bos taurus includes 22,000 genes, 80 per cent of which are shared with humans. Humans, researchers conclude, are closer to the bovine sequence than to those of mice or rats, which are far more commonly used as research subjects. That realization could open new vistas for human health research. The new data are especially important given the economic and nutritional importance of cattle to humans, said Dr. Casey. Focusing on genes that regulate milk synthesis in the cow, she also co-authored a companion report discussing how the bovine lactation genome sheds light on the evolution of mammalian milk.

We believe that milk evolved primarily as an immune function, Dr. Casey said, due in part to cow milks anti-microbial properties. After comparing the cattle genome data to that already assembled for other mammal species, the scientists concluded that milk is essential to the survival of newborn mammals and that the establishment of lactation mechanisms dates back more than 160 million years. Hereford, commonly used in beef production, was the breed of cattle selected for the sequencing study.

Scientists tag a gene that may explain hair loss

Researchers in Japan have identified a gene that appears to determine cyclical hair loss in mice and believe it may also be responsible for hair loss, or alopecia, in people. The scientists, led by Dr. Yumiko Saga of the Division of Mammalian Development at the National Institute of Genetics, described how they generated a line of mice that were lacking in the Sox21 gene.

The mice started to lose their fur from post-natal day 11, beginning at the head and progressing towards the tail region of the back, they wrote. Between day 20 and day 25, these mice lost all of their body hair, including the whiskers. Intriguingly, new hair regrowth was initiated a few days later but was followed by renewed hair loss. The cyclical alopecia continued for more than two years and the researchers observed that the mutant mice had enlarged oil-secreting sebaceous glands around the hair follicle and a thickened layer of skin cells during periods of hair loss.

The gene is likely involved with the differentiation of stem cells that form the outer layer of the hair shaft, wrote the researchers, who went on to examine human skin samples, where they found evidence of this same gene, indicating that the Sox21 gene could be responsible for hair loss conditions in humans.

Scientists identify gene in breast cancer pathway

Scientists at Albert Einstein College of Medicine (AECOM) of Yeshiva University, the United States, have discovered how a gene crucial in triggering the spread of breast cancer is turned on and off. The findings could help predict whether breast tumours will metastasize and also reveal potential drug targets for preventing metastasis.

A few years ago, AECOM scientists discovered a gene called zipcode binding protein 1 (ZBP1), which helps cells to move, grow and organize spatially. ZBP1 is very active in the developing embryo but largely silent in adult tissues, says Prof. Robert H. Singer, co-chair of anatomy and structural biology and co-director of the Gruss-Lipper Biophotonics Centre. He is one of ZBP1s discoverers and leader of the current study.

Researchers have subsequently found that ZBP1 is reactivated in several types of cancer, including breast, colorectal, and non-small cell lung cancers; but the gene is silenced in metastasizing cancer cells, as was shown by Dr. Singer and AECOMs Dr. John Condeelis, who also is co-chair of anatomy and structural biology and co-director of the Gruss-Lipper Biophotonics Centre.

The purpose of the current study was to find how the ZBP1 gene is activated and silenced, and how it influences the spread of breast cancer. After examining mouse, rat and human breast cancer cells, the scientists found that ZBP1 silencing occurs when a methyl group (CH3) attaches to ZBP1s promoter region (the segment of a gene where gene expression is initiated). The attachment of CH3 prevents the promoter from binding to a protein called beta-catenin; and without beta-catenin, the ZBP1 gene is effectively silenced.

The study, with Dr. Wei Gu as the lead author and Dr. Feng Pan a co-author, also showed that the silencing of ZBP1 increases cancer cells ability to migrate and promotes the proliferation of metastatic cells. The findings have important implications for forecasting breast cancer outcomes. According to the researchers, signs of ZBP1 silencing in breast cancer cells indicate that a breast tumour is likely to spread, information that would help in choosing a treatment strategy. The study also points to potential targets for drug treatment. The research team is investigating whether the ZBP1 gene in cancer cells could be reactivated and the cells prevented from metastasizing by selectively removing CH3 from ZBP1 promoter.

Discovering genes that protect against ageing

Scientists at the University of Liverpool, the United Kingdom, have developed a new method to help researchers identify genes that can help protect the body during the ageing process. They developed a method of analysing genes in multiple ageing tissue types in both animals and humans. The analysis, which included more than five million gene measurements, highlighted the mechanisms used by the body to protect against cellular changes with age that can result in conditions such as muscle degeneration and cognitive ageing.

The new method could help further understanding into anti-ageing interventions by identifying genes that indicate biological changes as a result of ageing. Research has suggested that some genes respond to age-related conditions by increasing key protein levels, allowing the body to manage the ageing process more effectively. Dr. Joao Pedro Magalhaes from the Universitys School of Biological Sciences explains: We developed a new algorithm to analyse microarray data of genes from different species, and combined data from multiple studies to obtain a picture of how genes respond to ageing in a whole organism. This method is similar to the way scientists study the molecular characteristics of cancer, but it is the first time it has been used to research ageing. The researchers wrote: We found that some genes previously unconnected with ageing become more abundant with age to help protect the body. We can use these genes as a biomarker or signature of ageing so that scientists can help develop products and treatments that help manage the ageing process effectively.

Genetic switch potential key to new class of antibiotics

Dr. Joseph E. Wedekind, an associate professor at the Department of Biochemistry and Biophysics at the University of Rochester Medical Centre, the United States, and colleagues have determined the structure of a key genetic mechanism at work in bacteria, including some that are deadly to humans, in an important step towards the design of a new class of antibiotics.

Researchers in Yale and New York Universities had reported in 2002 that regulatory mechanisms arising from riboswitches regulate gene expression at the level of messenger RNA (mRNA) by changing shape in ways that govern the genetic decoding process. The current study clarified, for the first time, the structure of natures smallest known riboswitch, and detailed how its structures control life processes in bacteria. Riboswitches typically work by turning off the ability of mRNA to decode genetic message. As riboswitches have not yet been found in human cells, and the hope is that future riboswitch drugs will kill bacteria without side-effects.

The current study looked at the preQ1 riboswitch that controls the ability of bacteria to produce a molecule called queuosine. In many organisms, queuosine or Q enables accurate gene expression by overcoming tRNA wobble, a built-in defect in the mRNA-ribosome-tRNA system charged with translating genes into proteins. Without Q many important bacteria lose their ability to produce gene products necessary for survival or to confer human disease.

Dr. Wedekind and colleagues solved the crystal structure of a preQ1 riboswitch in complex with its precursor metabolite preQ0. They chose to study the riboswitch from Thermoanaerobacter tengcongensis, a tough bacterium that lives at extreme temperatures and was first found in a Chinese hot spring.

The 3-D pictures that the scientists produced revealed fascinating insights about the riboswitch structure and preQ0 interactions. They show, for instance, that preQ0 binds into a buried pocket of the riboswitch, and achieves a structure usually associated with the stability of DNA or RNA chains. When the riboswitch twists into the double helix structure, the RNA that composes part of its structure aligns the bases in its chain such that they stack on top of each other, adding to their stability. Because preQ1 is a modified form of an RNA base, it stacks on the RNA bases in the riboswitch binding pocket with high affinity, adding stability to the switch that tightly locks up the mRNAs ribosome binding site.

The study further detailed how the first base of the mRNAs ribosome binding site binds to a loop of the riboswitch, the lever by which the ribosome-binding site is sequestered, and about how that binding empowers the switch to lock up, or sequester, the mRNAs ribosome binding site. The study also confirmed the preQ1 riboswitch to be uncommonly small, meaning its economical and elegant design accomplishes more function than expected for an RNA of this size.

The genetic legacy of alcoholism

An important genetic study conducted through Mayo Clinic, the United States, has identified vital new information concerning alcoholism in subjects with European ancestry. The research results indicate that alcohol dependence is highly inheritable, although specific genes and their variations associated with this illness remain unknown. Animal model studies allow identification of potential candidate genes but their relevance to alcoholism in humans and its complications, including alcohol withdrawal and seizures, require further research.

Under the direction of Dr. Victor Karpyak of the Mayo Clinic Department of Psychiatry and Psychology, a team of clinical and basic scientists investigated the sequence of the human MPDZ gene and its association with risks for alcohol dependence and alcohol withdrawal seizures.

Sophisticated genetic research in mice isolated small regions on mouse chromosomes linked to severity of acute alcohol and barbiturate withdrawal measured by the presence and severity of seizures. Further research demonstrated that MPDZ gene is the only one in this chromosome region that has variants associated with severity of acute alcohol and barbiturate withdrawal and seizures. The MPDZ protein is a key scaffolding brain protein, responsible for synaptic structure and plasticity. It is also known to be involved in learning and memory as well as seizures and epilepsy. Thus, it is a good candidate for the human study focused on genetic predictors for alcohol withdrawal. Unfortunately, little was known about sequence variability of the MPDZ gene in humans. It is also a very long gene and its sequencing required considerable effort and costs.

To investigate the relevance of the model findings in animals for human alcoholism, Dr. Karpyak and his colleagues resequenced the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures, 59 subjects with a history of withdrawal without seizures and 64 samples from non-alcoholic subjects all with European American ancestry. They discovered 67 new, mostly rare variants in the human MPDZ gene. Sequencing allowed the first opportunity of comparing MPDZ gene in humans and mice. The study found that the human gene does not have variations identical to those of the MPDZ gene associated with alcohol withdrawal seizures in mice.

Second, the researchers used common variants to compare haplotype structure of the MPDZ gene in alcohol-dependent subjects with and without a history of withdrawal seizures and in controls who did not have alcoholism. The study revealed a significant association between MPDZ gene variant alcohol dependency without seizures, compared with the control subjects. Contrary to initial hypothesis and animal findings, the study demonstrated no significant association between MPDZ sequence variants and withdrawal seizures in humans. This suggests the potential role of MPDZ in alcoholism and/or related phenotypes other than alcohol withdrawal seizures.


Special protein helps maintain an efficient brain

A study by researchers at the University of Wisconsin-Madison, the United States, has revealed that a section on synaptotagmin-IV (Syt-IV), a protein known to influence learning and memory, is necessary for maintaining an efficient brain. The study showed that Syt-IV keeps the strength of synapses connections between nerve cells where communication occurs within a useful range that is neither too strong nor too weak. The ability of synapses to adjust over time by becoming bigger and stronger or smaller and weaker their plasticity is at the heart of remembering, forgetting and learning. A delicate balance is required for this optimal brain plasticity.

The findings, published in Nature Neuroscience, may be useful in the future for treating neurodegenerative disorders such as Alzheimers and Parkinsons diseases, as well as epileptic seizures. Early stages of these disorders may stem from synaptic deficits. If a drug or genetic treatment could be designed to control Syt-IV expression and modify its effect on other key players involved in synaptic function, synapses might work better, says senior author Dr. Edwin R. Chapman, a Howard Hughes Medical Institute professor at the UW-Madison School of Medicine and Public Health (SMPH). Dr. Camin Dean, a post-doctoral fellow in Dr. Chapmans physiology department laboratory at the SMPH, did most of the work on the study.

In exploring Syt-IV, known for fluctuating up and down during the course of a typical day, the researchers first studied it in a cell culture and then in mice in which the protein had been knocked out. We quickly found that Syt-IV strongly affects multiple aspects of signal transmission, both pre- and post-synaptically, says Dr. Chapman, adding that the protein was not located where it was expected to be.

The researchers also performed standard experiments on the mice to test a phenomenon called long-term potentiation (LTP), the primary synapse-strengthening mechanism that promotes learning and memory. When we stimulate brain pathways heavily with this experiment, we see that synapses are reinforced and produce bigger responses, says Dr. Chapman. The synapses remember the stimulation, they learn something from it and we can see evidence of that. Despite the learning disabilities, the Syt-IV-free mice produced improved LTP. In fact, it was too high.

The researchers believe that Syt-IV serves as a way to maintain synaptic homeostasis or internal equilibrium by reigning in LTP to a normal level. The protein does its work indirectly by regulating brain-derived neurotrophic factor (BDNF), a growth factor crucial for long-term nerve cell well-being. In recent years, BDNF also has been shown to affect synapses. In the experiments, Syt-IV pulled down elevated LTP by restricting the release of BDNF on the receiving side of the synapse, gearing down synaptic activity.

Protein from algae shows promise for stopping SARS

A protein from algae may have what it takes to stop severe acute respiratory syndrome (SARS) infections, according to new research. The study found that mice treated with griffithsin (GRFT) protein had a 100 per cent survival rate after exposure to the SARS coronavirus (SARS-CoV), as compared with a 30 per cent survival for untreated mice. GRFT is thought to exert its anti-viral effects by altering the shape of the sugar molecules that line SARS-CoVs envelope, allowing it to attach to and invade human cells, where it takes over the cells reproductive machinery to replicate itself. Without that crucial ability, the virus is unable to cause disease.

The researchers led by Ms. Christine Wohlford-Lenane at the Department of Paediatrics, University of Iowa, the United States, and the lead author of the study treated experimental mice with GRFT or a sham treatment and then inoculated them with the SARS virus. They analysed the anti-viral activity of GRFT and the extent to which the virus was able to invade and replicate in the mice at 2, 4 and 10 days after infection. They found that mice who had not been treated with GRFT showed 20 times more plaque-forming units of virus than treated mice.

They also noted that the lungs of untreated infected mice showed extensive necrotizing bronchitis and prominent oedema, while mice treated with GRFT showed evidence of significantly less severe lung damage. Further, mice treated with GRFT did not experience the drastic weight loss of untreated mice, which lost 35 per cent of body mass. This indicates that not only did the GRFT stop the virus from replicating, but also prevented secondary outcomes, such as weight loss, that are associated with infection, said Ms. Wohlford-Lenane.

How protein controls cancer cell migration

Focal adhesion kinase (FAK) co-ordinates how cancer cells move while at the same time staying attached to a surface, according to a group of investigators from the University of Wisconsin, the United States. The scientists, let by Dr. Keefe T. Chan from the Department of Molecular and Cellular Pharmacology, report that FAK controls movement by balancing the number of invadopodia that create a path for migration and the number of focal adhesions that hold the cell back.

It has been known that FAK spurs focal adhesions to disengage and that it is more abundant in metastatic tumours. It was also understood that cancer cells can send out extensions called invadopodia, which release enzymes that dissolve the extracellular matrix (ECM) and clear a path for the cell to move through. As they move, cancer cells gain traction by temporarily attaching to the ECM through focal adhesions. The new study, which appears online in the Journal of Cell Biology, sought to understand whether FAK also regulates invadopodia.

The team removed FAK and found that breast cancer cells were much less invasive. To their surprise, however, the FAK-lacking cells sprouted extra invadopodia. The cells also sported large focal adhesions that were particularly sticky. The group observed that in FAK-lacking cells, FAKs helper protein, Src, localized near invadopodia. Src usually works with FAK to phosphorylate tyrosines in proteins like paxillin which then disassemble the focal adhesion. The scientists found that in cells missing FAK, the phosphorylated proteins accumulated in invadopodia. The next question, the researchers say, is how FAK and Src integrate these events to promote invasion.

Heart protein regulates blood vessel maintenance

In a study led by Dr. Akiko Hata of Tufts University School of Medicine, the United States, scientists have shown that four-and-a-half LIM domain protein 2 (FHL2), a protein expressed in the heart, inhibits the genes necessary for the quiescence of vascular smooth muscle cells (vSMCs), which line blood vessels.

In diseases such as atherosclerosis or normal tissue damage caused by balloon angioplasty, vSMCs undergo a process where they transit between a resting state and a proliferative state. The ability to transit between the two states is necessary for the normal development of blood vessels, regulating blood pressure, and repairing vessels that suffer from injury.

By understanding the pathways that modulate vSMCs, we are closer to being able to develop reagents to ameliorate abnormal function of blood vessels, says Dr. Hata. The researchers have previously shown that bone morphogenetic proteins (BMPs) play a role in the maintenance of SMCs in the pulmonary artery. In this study, the research demonstrates that FHL2 inhibits activation of genes that are involved in contraction of SMCs by at least one of the BMPs. They found that FHL2 is important in the regulation of vasomotor tone, or the contraction and relaxation of muscles in the blood vessel, the dysfunction in which is thought to cause high blood pressure.

Brain protein key to Parkinsons, drug addiction

Scientists have identified a protein that appears not only to be central to the process that causes Parkinsons disease but could also play a role in muting the high from methamphetamine and other addictive drugs. The action of the protein, known as organic cation transporter 3 (oct3), fills a longstanding gap in scientists understanding of the brain damage that causes symptoms like tremor, stiffness, slowness of movement and postural instability. In a paper published online in the Proceedings of the National Academy of Sciences, scientists at the University of Rochester Medical Centre and Columbia University, the United States, have shown that oct3 a protein that shepherds molecules into and out of cells plays a critical role, bringing toxic chemicals to the doorstep of the brain cells that die in patients with Parkinsons disease. Oct3 is involved in the brains response to addictive drugs like methamphetamine as well.

Symptoms of Parkinsons stem from the death of a very small, specialized group of brain cells called dopamine neurons. For decades, scientists have been trying to understand why those cells die. The current study supports a role for astrocytes, a type of cell that is the most common in the brain and identified as a player in Alzheimers disease, amyotrophic lateral sclerosis, epilepsy, and other diseases.

Dr. Kim Tieu of University of Rochester Medical Centre, a corresponding author of the paper, had earlier studied how the brain handles MPTP, a chemical that ultimately damages the same brain cells that are injured in patients with Parkinsons disease. Scientists use MPTP as a model for the disease because it causes an identical type of brain damage. In the brain, MPTP is converted primarily in astrocytes to MPP+, a chemical that is deadly to dopamine neurons.

The current study fingers oct3 as the shepherd that escorts toxic MPP+ out of the astrocytes and into the space surrounding dopamine neurons. That is where another molecule known as the dopamine transporter brings it into the neuron itself. When the team blocked or genetically removed oct3 in mice, the dopamine neurons in the brains did not die despite the presence of MPTP in the brain. Without oct3, MPP+ were confined inside astrocytes and did not affect the dopamine neurons. When oct3 was present in the usual amounts, dopamine neurons died as expected.

The team also showed that oct3 plays a role in the brains response to methamphetamine. Oct3 is critical for helping astrocytes soak up excess dopamine in the space around neurons. When dopamine is not removed as quickly or thoroughly as usual, people can feel euphoric, but they can also experience serious brain damage.


Stem cell transplantation helps diabetics become insulin-free

The majority of patients with type 1 diabetes who underwent a certain type of stem cell transplantation became insulin-free, with good glycaemic control, and also increased C-peptide levels, an indirect measure of beta-cell function, according to a recent study led by Dr. Richard K. Burt of the Northwestern University Feinberg School of Medicine, the United States. Clinical evidence indicates an inverse association between beta-cell preservation and function and chronic complications of type 1 diabetes mellitus (DM), and the higher the C-peptide levels, the lower the incidence of some types of complications of type 1 DM.

A previous study had found that autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in 15 patients with newly diagnosed type 1 DM resulted in the majority of patients becoming insulin free during the follow-up, which averaged about 19 months. HSCT, which uses a patients own blood stem cells, involves the removal and treatment of the stem cells, and their return to the patient by intravenous injection.

Dr. Burt and colleagues conducted a study to determine if post-transplant insulin independence was due to improved beta-cell function and found that of the 23 patients, 20 experienced time free from insulin (12 continuously and 8 transiently). Patients remained insulin-free for an average of 31 months (range, 14-52 months). Eight patients relapsed and resumed insulin use at low doses. The majority of patients achieved good glycemic control. Following long and sustained monitoring, Dr. Burth and colleagues concluded that autologous non-myeloablative HSCT is able to induce long and significant increases of C-peptide levels associated with absence of or reduction of daily insulin doses.

Common virus may cause high blood pressure

A common virus may be a major cause of high blood pressure, researchers have said in a finding that may bring new approach to treating hypertension. Based on a series of studies in mice, they said cytomegalovirus or CMV a herpes virus that affects some 60 to 99 per cent of adults globally appears to increase inflammation in blood vessels, causing high blood pressure. When combined with a fatty diet, CMV may also cause hardening of the arteries, a major risk factor for heart attacks, strokes and kidney disease.

Dr. Clyde Crumpacker of Harvard Medical School and Beth Israel Deaconess Medical Centre, the United States, said the research offers the first direct proof of the virus causing persistent infection in blood vessels. He said the study suggests vaccines and antiviral drugs may offer a new approach at treating hypertension.

In experiments, Dr. Crumpacker and colleagues found elevated blood pressure in lab mice infected with the virus. Significantly, 30 per cent of infected mice on a high-fat diet also had signs of atherosclerosis, strongly suggesting that the CMV infection and the high cholesterol diet might be working together. In another study of kidney cells in infected mice, the team found high levels of the enzyme renin, which is known to cause high blood pressure. They found the same high rates of the enzyme in human blood vessel cells infected with CMV.

Key to potential treatment for allergy-induced asthma

In a research that could lead to new asthma drugs, scientists at Yale School of Medicine, Hydra Biosciences Cambridge and University of California San Francisco, the United States, have found that a protein may be a trigger for allergy-induced asthma in mice. They also demonstrated how a drug known to reduce inflammatory and neuropathic pain may also inhibit asthma symptoms in mice. The new study tracks the role of the ion channel protein TRPA1. While the exact function of TRPA1 in the airway inflammation of asthma is not completely understood, scientists do know from previous research that this protein is a sensor for chemical irritants such as cigarette smoke and certain chemicals that also trigger asthma. TRPA1 is found in airway nerves that mediate pain and irritation, as well as trigger coughing and sneezing.

The researchers found that mice with no TRPA1 showed fewer signs of asthma. When compared to normal mice, those lacking the gene for TRPA1 had greatly diminished inflammation, airway mucus and bronchoconstriction, said the papers lead author, Dr. Sven-Eric Jordt, assistant professor of pharmacology at Yale School of Medicine. Moreover, administration of HC-030031, a pharmacological agent that inhibits pain related to TRPA1, to mice with asthma reduced their symptoms. Blocking TRPA1 may prevent the infiltration of the lung by the inflammatory cells responsible for asthma symptoms such as wheezing and mucus overproduction, Dr. Jordt explained.

Biodegradable gel as a treatment for oesophageal cancer

Gastroenterologists at Rush University Medical Centre, the United States, are studying the safety and efficacy of a new chemotherapy system for patients with oesophageal cancer. The unique drug therapy delivers a highly concentrated dose of chemicals injected directly on to the hard-to-reach tumours in the oesophagus non-surgically. Scientists at Rush are trying to determine if the gel treatment can reduce the size of the cancerous tumours.

The experimental drug, called OncoGel, is made of two major components, the ReGel drug delivery system a gel made up of ingredients used in biodegradable stitches, and paxclitaxel, a well established, FDA-approved anti-cancer chemotherapy agent. Patients receive a one-time injection of OncoGel during an endoscopy. Pilot studies showed OncoGel as continuously releasing the chemotherapy agent paclitaxel in concentrated doses at a higher magnitude than in just delivering it through the blood for up to six weeks, reports Dr. Sohrab Mobarhan, the studys principal investigator and clinical director of the Coleman Foundation Comprehensive Clinic for Gastrointestinal Cancers.

Octopus venom can treat allergies, cancer

An understanding of the structure and mode of action of venom found in all octopuses, cuttlefish and some squid can help design drugs for the management of pain, allergies and cancer. The scientists led by Dr. Bryan Fry, a biochemist at the University of Melbourne, Australia, analysed the genes for venom production from different species of octopus and found that a venomous ancestor produced one set of venom proteins, but over time, additional proteins were added to the species chemical arsenal.

The origin of these genes also sheds light on the fundamentals of evolution, presenting a prime example of convergent evolution where species independently develop similar traits. The team will now work on understanding why very different types of venomous animals seem to consistently settle on the similar venom protein composition, and which physical or chemical properties make them predisposed to be useful as toxin.

Stem cell therapy may cure blindness

Scientists in the United Kingdom has developed a treatment that involves replacing a layer of degenerated cells with new ones generated from embryonic stem (ES) cells to cure age-related macular degeneration (AMD), the most common cause of blindness. According to the scientists, in 6-7 years time, it will become a routine, one-hour procedure. In the new therapy, ES cells are transformed into replicas of the missing cells. They are then placed on an artificial membrane that is inserted in the back of the retina. Laboratory trials completed by the scientists have shown that ES cells can prevent blindness in rodents with a disease similar to AMD. They have also successfully tested elements of the technology in pigs.

Lead scientist Prof. Pete Coffey from University College London said the treatment would take less than an hour, so it really could be considered as an outpatient procedure. Dr. Peng Khaw of Moorfields Hospital, a team member, added that stem cell therapy offers a great hope for the patients around the world who cannot be treated with conventional treatment. Pfizer, the pharmaceutical research company, will financially back bringing the new therapy to patients.


HIV vaccine from genetically engineered plants

A research team at Swedens rebro University has succeeded in changing the genes in plants so that they can function as a vaccine against human immunodeficiency virus (HIV). Through genetic modification, the plants have acquired the capacity to produce a protein that is part of the virus. Mice that have been fed the plants have reacted and formed antibodies against the HIV protein.

As the HIV virus mutates rapidly, it is not possible to create an effective vaccine that is based on the entire virus. Instead, the researchers selected a protein, p24, that exists in all HIV viruses and looks roughly the same in the various virus lines, says Dr. Ingrid Lindh, author of the study. To get plants to produce the p24 protein, the gene that underlies the process must be a part of their own genetic make-up. As it is impossible to transfer the gene directly from the virus to the plant, the researchers first placed the gene into a bacterium that was then transmitted to the plants. The plants produced p24 and also passed on this ability to their off-springs.

In the next phase, mice were fed with the p24 plants. The mices immune defence reacted just as the researchers had hoped, producing antibodies against the protein. In other words, this functioned as a vaccine. This raises hopes that a similar reaction in humans would make them immune to HIV. To increase the potency of the vaccine, these scientists are plan to add more HIV proteins together with other compounds that reinforce the bodys reaction to HIV-specific proteins. In parallel with this, they will work to select a suitable vegetable that is easy to cultivate in different climates and is readily accepted in different cultures.

Bt brinjal completes final field testing

With the completion of the final round of field testing of the Basillus thuringiensis (Bt) brinjal (eggplant or aubergine), the biotechnologists at Krishi Vigyan Kendra (KVK), India, have claimed success in eradicating the fruit and shoot borer (FSB) menace, besides ensuring safety of consumers and environment. The Bt varieties and their non-Bt counterparts were subjected to critical observation for level of expression of Cry1Ac protein, FSB infestation, occurrence of beneficial and non-target insects all through the trial period in regular intervals.

FSB is the most damaging pest on brinjal crops and conventional management methods have not succeeded in mitigating its infestation in eggplant. Biotechnology provided the tools for precision Bt gene transfer that yielded a line of the vegetable with sustainable resistance to FSB. Close to its commercial release, the Bt brinjal is the first Bt vegetable crop in India and the first brinjal variety in the world. In addition to reduction in pesticide usage, minimization of yield loss and economic benefits, experts believe that Bt brinjal has a significant role in improving the nutrition status of the masses, since it is one of the largest produced and consumed vegetables in the country.

Golden rice an effective source of vitamin A

The beta-carotene in golden rice converts to vitamin A in humans, according to researchers at Baylor College of Medicine (BCM) and Tufts University, the United States. Golden rice was developed in the early 1990s with the goal of creating rice that had beta-carotene a vitamin A precursor in the rice grain. In its current form, golden rice contains 35 micrograms of beta-carotene per gram. We found that four units of beta-carotene from golden rice convert to one unit of vitamin A in humans, said Dr. Michael Grusak, associate professor of paediatrics at the Childrens Nutrition Research Centre at BCM.

The scientists determined this by feeding five healthy adults a predetermined amount of specially labelled golden rice and measuring the amount of retinol, a form of vitamin A, in the blood. However, more research is necessary before golden rice is made commercially available. The next steps of the research include incorporating this technology into the rice grains found in various regions and continuing testing the conversion rates in humans.

Engineered corns vitamin boost

A genetically modified (GM) corn (maize) fortified with three vitamins has been created by European scientists. The modifications make the growing maize produce large amounts of beta carotene and precursors of vitamin C and folic acid. The development marks the first time any plant has been engineered to make more than one vitamin. The team, led by Dr. Paul Christou from Spains University of Lleida, transferred genes into immature embryos of a variety known as M37W. The embryos were bombarded with metal particles coated with chunks of DNA that, if taken up by the embryo, would alter its internal biochemical processes to make it produce the vitamins.

Subsequent analysis of sample plants grown from the GM seeds showed that the maize was indeed successfully manipulated into producing the vitamins. The changes induced in the corn also persisted through a couple of generations of the plants. The yield of vitamins vastly exceeds any produced by conventional plant breeding methods write the researchers from universities in Spain and in Germany. The researchers state that those eating 100-200 g of the fortified maize would get almost all their recommended daily allowance of vitamin A, and folic acid and 20 per cent of the ascorbate they need.

Gene that allows plants to survive through stress

An international team of scientists has identified a key gene that allows plants to defend themselves against environmental stresses like drought, heat and freezing. Plants have stress hormones that they produce naturally and that signal adverse conditions and help them adapt, said team member Dr. Peter McCourt, a professor of cell and systems biology at Canadas University of Toronto.

The researchers, led by Dr. Sean Cutler from University of California Riverside, the United States, have identified the receptor of the key hormone in stress protection called abscisic acid (ABA). Under stress, plants increase their ABA levels, which help them survive a drought through a process not fully understood. A receptor is a protein molecule in a cell to which mobile signalling molecules may attach. Usually at the top of a signalling pathway, the receptor functions like a boss relaying orders to the team below that then executes particular decisions in the cell. The scientists used a new approach called chemical genomics to identify a synthetic chemical, designated pyrabactin, which specifically activates an ABA receptor in the model laboratory plant Arabidopsis. With pyrabactin in hand, it was now possible to directly identify the ABA receptor

Virus-resistant GM potato, groundnut under trial stage

In India, genetically modified (GM) virus-resistant potato and groundnut, and drought and salinity-tolerant rice are under various stages of trials. The programme is spearheaded by the Agricultural Biotechnology Support Project -II (ABST-II) of the Cornell University, the United States, which helped the development of brinjal resistant to the fruit and shoot borer and led to its commercialization.

For fighting the dreaded late blight virus in potatoes, ABST-II has assisted the transfer of Rb gene to the Central Potato Research Institute (CPRI). The gene was isolated from a wild relative of potato by the researchers at the University of Wisconsin, the United States, and incorporated into a popular potato variety in that country. CPRI has transferred the Rb gene to two popular varieties kufri jyothi and kufri bahar. These will be field-evaluated during May-June 2009.

Cornell Universitys College of Agriculture and Life Sciences, and Donald Danforth Plant Sciences Centre, the United States, teamed up with Acharya N.G. Ranga Agricultural University, the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), and the National Bureau of Plant Genetic Research (NBPGR) to develop transgenic groundnut with ability to fight tobacco streak virus (TSV). Two varieties of groundnut plants were developed and were being evaluated in green house. Under ABST-II the trehalose gene has been transferred to the Directorate of Rice Research to be introduced into local rice varieties and screen them for drought tolerance.


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