VATIS Update Biotechnology . May-Jun 2004

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Biotechnology May-Jun 2004

ISSN: 0971-5622

VATIS Update Biotechnology is published 4 times a year to keep the readers up to date of most of the relevant and latest technological developments and events in the field of Biotechnology. The Update is tailored to policy-makers, industries and technology transfer intermediaries.

Co-publisher: Biotech Consortium India Ltd
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European Commissions nod to import of GM sweet corn

The European Commission (EC) has authorized the import into the European Union (EU) of sweet corn made from Syngentas genetically modified maize line called Bt11. The decision effectively ended the ECs unofficial moratorium on GM foods, which had been in place for over five years, during which time no new GM food was approved for use.

Grain from the GM maize line Bt11 had been authorized for import into Europe since 1998 and was widely used in EU countries in feed and in derived food products such as maize oil, maize flour, sugar and syrup, snack foods, baked foods, fried foods, confectionery and soft drinks. The authorization now covers specific use for imports of canned or fresh sweet corn (maize).

Under strict EU laws, any import of the canned sweet corn would have to show clearly on the labelling that the corn had been harvested from a genetically modified plant. The new EU rules on GMOs require clear labelling and traceability. Labelling provides consumers with the information they need to make up their own mind. They are therefore free to choose what they want to buy. It is a responsible move by the EC based on stringent and clear legislation. , 19 May 2004

Human genome-wide RNAi library for research

A group of scientists led by Dr. Greg Hannon of Cold Spring Harbor Laboratory (CSHL), New York, the United States, has announced the creation of the first library of human RNA interference (RNAi) clones, which would eventually provide users the ability to shut off virtually every gene in the human genome. Based on short-hairpin RNA (shRNA), a versatile and powerful method for triggering RNAi, the library is the first DNA vector-based, human genome-wide RNAi library that is sequence-verified. Several leading pharmaceutical companies have entered into agreements with CSHL to take advantage of the strong potential for therapeutic discovery that this powerful library promises to deliver.

RNAi phenomenon has the potential to shut off only individual genes. By individually targeting more than 10,000 human genes through this sequence-based method, companies could rapidly identify and validate target genes that cause disease, and develop drugs to hit those targets.
The shRNA method developed by Dr. Hannon and his colleagues is one of the most efficient method for triggering RNAi and has been validated in a large number of studies with different animal and human cell cultures, as well as in whole animals, where the method has been shown to trigger stable, heritable gene silencing. In addition, the sequence-validated library of shRNA molecules targets each one of more than 10,000 different human genes in triplicate, with three different gene-specific interfering RNAs. According to Dr. Hannon, the method could be adopted by pharmaceutical and biotechnology industries to systematically search for targets for new drugs for cancer and other diseases. , 29 March 2004

Indian DNA rabies vaccine gets clearance for trials

The Drug Controller General of India (DCGI) has cleared for animal trials a novel combination vaccine for rabies developed jointly by the Bangalore-based Indian Institute of Science and Indian Immunologicals Ltd. of Hyderabad, India. Although the research was for the development of rabies vaccine for both veterinary and human use, the clearance from DCGI was granted only for conducting trials for the veterinary version on dogs and cattle. DCGI granted permission after being satisfied with the pre-clinical toxicity studies on animals conducted at the National Institute of Nutrition, Hyderabad, India.

The rabies vaccine is the worlds first combination vaccine containing DNA vaccine, and its trial is being held at all the veterinary institutions of India. The final data are expected in about three months. The combination vaccine, which would cost much less than the existing ones in the market, has two components: DNA encoding rabies virus surface glycoprotein (DNA vaccine) and a small quantity of inactivated rabies virus. The presence of DNA is expected to increase the stability as well as shelf life of the vaccine. Indian Immunologicals plans to sell it under the brand name Dinarab.

The research project for the DNA rabies was an industry-institute initiative, which spanned over a period of two years and was funded mainly by Indian Immunologicals. The Department of Biotechnology, Government of India, provided additional funding of US$100,000 under the Prime Minister Jai Vignan Vaccine Mission Programme for the pre-clinical toxicology studies, which are expected to be continued until the final trial on animals are completed. The rabies vaccine has received a PCT Patent from South Africa and the patent application made in 2003 is pending before the European Patent Committee.

Researchers step closer to creating oral insulin

Researchers at the University of Toronto, Ontario, Canada, have demonstrated that certain designer molecules can interact with the bodys insulin receptor, a step towards the development of an oral medication for diabetes. They have created the first small molecules using the 3-D structure of the insulin receptor. A receptor is the site on the surface of a cell to which molecules with specific tasks, such as hormones, attach themselves. Insulins task is to initiate the utilization of sugar in the blood.

This is the first time that a 3-D model of the insulin receptor on a cell surface has been created and used for drug design. The 3-D computer modelling of the receptor and the drug design were conducted at University of Torontos Molecular Design and Information Technology Centre. This knowledge was then used by the researchers to create specially designed molecules, which bind to the receptor in the same way that insulin does. In so doing, they hope to develop a drug similar to insulin that could be taken orally.

Express Pharma Pulse, 8 April 2004

DBT sanctions US$4.4 million for biotech incubator centre

The Government of Indias Department of Biotechnology (DBT) has sanctioned US$4.4 million for setting up a biotechnology incubator centre (BTIC) at Hyderabad. The first Indian biotech incubation centre is being set up by the Institute of Chemical Technology (IICT) at the Shapoorji Pallonji Biotech Park in Hyderabad, Andhra Pradesh. The equity base of BTIC, which would provide assistance to start up biotech companies, might be increased by an additional US$1.1 million through private participation. The centre is the result of a strategic linkage established by DBT, the Department of Industries and Commerce, the Government of Andhra Pradesh and the Council of Scientific & Industrial Research, seeking the growth potential of biotechnology-based industries in the state.

The incubator would provide opportunities in areas of enzymes, organic intermediates, antibiotics, recombinant proteins, biopharma products, primary and secondary metabolites and biospecialities. R&D and industry relations would grow through the incubator, as incubators play a key role in developing new ideas and making those ideas viable. IICT is expected to make BTIC operational within two years.

Chronicle Pharmabiz, 8 April 2004)

Stem cell store opens in the United Kingdom

The worlds first stem cell bank, hosted by the National Institute for Biological Standards and Control, Hertfordshire, the United Kingdom, has received its first deposits. The bank will grow and store stem cells for use in medical research. The first two stem cell lines to be banked are from Kings College in London and the Centre for Life, a research facility in Newcastle upon Tyne. These stem cell lines were derived from early human embryos, from tissues donated by patients undergoing fertility treatments.

Stem cells are the fundamental building blocks of the body, and have the potential to become many different types of cell, thus helping to repair diseased and damaged tissues. Cell and animal studies have shown that stem cells could turn into brain, heart, muscle and skin. The cells can reproduce indefinitely in culture, enabling researchers to grow billions of cells for storage and research.

The stem cell bank is unique as it plans to store the full gamut of stem cell lines: embryonic, foetal and adult. Stem cells can be found in the body throughout life, and the different types are thought to have varying degrees of versatility.

Researchers plan to study them all, in the hope of developing a range of related therapies. According to Mr. Colin Blakemore, chief executive of the Medical Research Council, the United Kingdom, which co-funded the project with the Biotechnology and the Biological Sciences Research Council, the bank would ensure that researchers get to explore the enormous potential of this exciting science for the future benefit of patients. , 20 May 2004

Rasi Seeds to launch Bt-cotton

Rasi Seeds Ltd. based in Tamil Nadu, India, has become the second Indian company to receive approval from Genetic Engineering Approval Committee (GEAC) for the commercial cultivation of Bt-cotton. This approval extends for cultivation in the central and southern parts of the country using the RCH2 Bt variety of cottonseed developed by the company.
Rasi Seeds is launching Bt-cotton seeds from Kharif (rain-fed crop) season this year. It has taken four years to launch Bt-cotton seeds in India. The GEAC had deferred a decision on the application of Rasi Seeds, a sub-licensee of the Bt cotton technology that was acquired by Mahyco from Monsanto, the United States, for seed production of transgenic cotton hybrids RCH-134 and RCH-138 because of non-availability of basic data.

According to Mr. Jaikumar, Vice President, Marketing, Rasi Seeds would release approximately 300,000 packets of Bt-cotton seeds in six states Andhra Pradesh, Gujarat, Karnataka, Madhya Pradesh, Maharashtra and Tamil Nadu at the prevailing market price of US$35.30 per packet. He is optimistic about the growth of the Bt-cotton market in India, as that would benefit the farmer by reducing the cost of insecticides, reduce pollution from use of insecticides and also increase the yield of cotton.

BioSpectrum, May 2004


Human Genome Sciences looks towards India

Human Genome Sciences Inc., based in Maryland, the United States, showed interest in the Indian biotech industry at the Global Partnering Summit held recently in New Delhi. The company is looking at opportunities to work together with Indian pharmaceutical and biotechnology companies for the discovery and development of new pharmaceutical products.

According to Dr. William A. Haseltine, Founder and CEO of Human Genome Sciences, India was showing enormous change in its approach and its biotechnology industry offered immense opportunities for the domestic as well as overseas firms. He said that there was a vast skilled labour owing to the countrys deep commitment to higher education, and good infrastructure for the biotech industry. He stressed upon the need to establish strong and aggressive venture capital fund for the Indian biotech industry and research. According to him, European companies from France and Sweden, among others, formed the backbone of capital investment in the United States biotech industry and the same could be brought to India. The company was looking for collaborations with Indian biotech firms for the development of gene therapy products, small molecule drugs and diagnostic products discovered using its genomics-based technology.

BioSpectrum, April 2004

Bionomics files international patent for cancer gene portfolio

Bionomics Limited, an Australian biotechnology company based in Adelaide, has filed an international patent application covering 496 proprietary angiogenesis drug targets. The international patent application would apply to genes that Bionomics has identified using advanced technologies such as microarray and bioinformatics analyses. These technologies have enabled Bionomics to identify novel angiogenesis genes that have not been identified by other companies or research groups. The patent application claims that these genes are potentially valuable targets for drugs that treat cancer by inhibiting blood vessel growth in tumours. The patent application extends to cover a range of drugs that may be developed for these genes, including therapeutic antibodies.

According to Dr. Deborah Rathjen, Bionomics is responding to the substantial market opportunities represented by the new approaches to treating cancer by inhibiting angiogenesis. By identifying new drug targets for angiogenesis, Bionomics is in a strong position to meet the needs of pharmaceutical companies and biotechnology companies that were developing this new class of anti-cancer treatments.

Chronicle Pharmabiz, 8 April 2004

Amgen to acquire Tularik for US$1.3 billion

In California, the United States, Amgen Inc., the largest biotechnology company, signed a definitive merger agreement with Tularik, a pioneer in drug discovery related to cell signalling and the control of gene expression. Tularik Inc., also based in California, would become a wholly owned subsidiary of Amgen after the acquisition. The value of the transaction, expected to close in the second half of 2004, was estimated to be approximately US$1.3 billion.

Amgen expects that this transaction would represent an incremental increase of approximately US$100 million per year in Amgens investment in R&D for the next several years. Amgen and Tularik have complementary chemistry expertise and compound libraries that could together strengthen as well as broaden their discovery capabilities.

BioSpectrum, April 2004

Intas Pharma enters biotech drug market

Intas Pharmaceuticals Ltd. based in Ahmedabad, India, will be entering the biotech drugs market with the launch of its G-CSF (granulocyte colony stimulating factor) in June this year. G-CSF has received approvals from the Department of Biotechnology and other regulatory authorities. This would be followed by other products such as erythropoietin, interferon, interleukins and human growth hormones.

According to the company, the estimated domestic market for G-CSF, erythropoietin and interferon is about US$21 million. Intas has a ready-to-produce manufacturing facility with an area of 8,000 sq. ft. near Ahmedabad. It is expecting revenue of US$22 million in the next three years from its biotech products.

Chronicle Pharmabiz, 29 April 2004

Shreya to enter insulin market

Shreya Life Sciences Ltd., Mumbai, the Indian subsidiary of the Russian Shreya Group based in Moscow, would soon be entering the domestic and export markets for recombinant insulin. The company has already started setting up a plant in Pune for production of human insulin. Targeting an overall growth in both pharma and bio-pharma in the years to come, the company is also planning significant investments in the basic R&D. According to Mr. Sujit Kumar Singh, Chairman and Managing Director of the company, close to 50 per cent of their earnings come from the export markets. Shreya Life Sciences is planning to strengthen its base in the areas of biotech and R&D, and expects an income of US$70 million for 2004-2005.

Chronicle Pharmabiz, 8 April 2004

Cipla and Avesthagen in pact for biopharmaceuticals

In India, the Mumbai-based Cipla Ltd. and Avestha Gengraine Technologies Ltd. have embarked on a collaborative biopharmaceuticals development programme for a new generation of targeted therapies. The partnership would initially focus on development of biopharmaceuticals in the area of autoimmune disorders and is expected to widen, with a bouquet of products in the pipeline to cater to other segments, such as cancer. The first bio-therapeutic product is expected within the next three years.

Under the agreement, Avesthagen would focus on the research and product development all the way through clinical trials while Cipla would concentrate on scale-up, marketing and distribution. The Indian biopharmaceutical business, presently estimated at US$200 million, is expected to grow to around US$3.3 billion by 2007-2008, dominated by recombinant proteins, vaccines and monoclonal antibodies. The Avestha-Cipla tie-up hopes to capitalize on this opportunity as a base to catapult it into markets abroad. , 12 May 2004


Whole genome microarrays for comparative genomics

Library on a Slide a novel application of microarray technology developed by Dr. Lixin Zhang and his colleagues at the University of Michigan, the United States would help researchers compare the genetic make-up of large numbers of bacterial strains to discover which genes are responsible for causing disease. Up to 30,000 whole genomes could be printed on a single slide using this product. The most vital characteristic of the Library on a Slide is that each spot on the slide contains the genomic DNA of one bacterial strain, rather than containing multiple copies of a single gene.

The researchers adapted a novel high-throughput method for isolating small DNA fragments to efficiently isolate high quality genomic DNA, and then optimized the conditions for printing that genomic DNA at high density onto a glass slide. They predict that their method would be an efficient and cost-effective way for sharing and utilizing large strain collections in comparative genomics studies. The scientists also tested techniques for identifying individual target genes at high sensitivity using fluorescently labelled probes. For testing the Library on a Slide method, the group created a sample array using a collection of E. coli genomes, and probed it to discover which genomes contained the hemolysin gene, a known virulence factor. The results from the array experiment perfectly matched with results from experiments using dot blot and Southern hybridization methods.

The researchers have envisaged other ways that their technique could develop. According to them, a single Library on a Slide could also be constructed with isolates from several related species, or species that are part of a microbial ecosystem. Such a platform would enable the examination of the extent of shared genetic elements across species, especially horizontally transferred virulence factors and antibiotic resistance genes. , 22 March 2004

Bio-computer diagnoses cancer and produces drug

The worlds smallest computer, made entirely of biological molecules, was developed by a team of scientists led by Prof. Ehud Shapiro at Weizmann Institute of Science, Rehovot, Israel. This computer was successfully programmed to identify in a test tube, changes in the balance of molecules in the body that indicated the presence of certain cancers, to diagnose the type of cancer, and to react by producing a drug molecule to fight the cancer cells.

Input, output and software of the biological computer were all composed of DNA, while DNA-manipulating enzymes were used as hardware. The input apparatus was designed to assess concentrations of specific RNA molecules, which might be over- or under-produced, depending on the type of cancer. Using pre-programmed medical knowledge, the computer then made its diagnosis based on the detected RNA levels. In response to a cancer diagnosis, the output unit of the computer could initiate the controlled release of a single-stranded DNA molecule that was known to interfere with the cancer cells activities, causing it to self-destruct.

In one series of test-tube experiments, the team programmed the computer to identify RNA molecules that indicated the presence of prostate cancer and, following a correct diagnosis, to release the short DNA strands designed to kill cancer cells. Similarly, they were able to identify, in the test tube, the signs of one form of lung cancer. The scientists hope to create a doctor in a cell, which will be able to operate inside a living body, spot disease and apply the necessary treatment before external symptoms even appear. , 28 April 2004


Rat genome reveals supercharged evolution

The genome of Rattus norvegicus (brown Norway rat) has been successfully sequenced by a team of scientists guided by Dr. Richard Gibbs of the Baylor College of Medicine, Houston, Texas, the United States. This is only the third mammal after humans and mice to have its genetic plan read. R. norvegicus has 2.75 billion pairs of DNA bases, which is slightly fewer than our 2.9 billion and slightly more than the mouses 2.6 billion. The genome analysis showed that humans, rats and mice have about the same number of genes. It also revealed that humans and rodents went out separate ways from a common ancestor about 80 million years ago, with rats and mice diverging between 12 and 24 million years ago. Even today, all three species share 280 large chunks of chromosomes that are virtually identical, suggesting that they are indispensable. These one billion or so bases form an ancestral core.

The genetic analysis revealed that almost all the human genes linked with disease so far are identical in rats too, validating the use of rats in their experiments. The availability of the rat genome, covering 90 per cent of its genetic code, would accelerate research on the genetic roots of inherited disorders in humans and would speed the creation of treatments. The identification of disease genes would in many cases be five fold quicker with a rat genome sequence. Comparisons between the genomes also yield insights into how each species had evolved.

The analysis revealed that rats had been evolving faster than both humans and mice. The regions evolving fastest are those associated with the rats acute sense of smell and its use in detecting danger, marking territory and choosing mates. Rats have an estimated 2,070 smell receptor genes, about a third more than mice, and also produce more pheromone scents. Rats are also ahead in the evolution of genes that helped them detoxify chemicals in their livers and elsewhere. By knocking out genes, it might be possible to genetically engineer rats so that their detoxification machinery was identical to that of humans, improving the predictive accuracy of toxicology and drug safety testing. , 31 March 2004

Shared gene switch for all plants found

Researchers led by Dr. Sandra Floyd and Dr. John Bowman at the University of California, the United States, have found a gene-switching mechanism dating back 400 million years to the very first plants that made it onto land. According to them, a family of genes required for stem and leaf development in flowering plants is controlled in the same way in everything from mosses to a Douglas fir. The gene switching mechanism depended on microRNAs, short pieces of RNA that switch genes off by interfering with messenger RNAs that are produced when genes are read.
The researchers looked at a family of genes found in all major groups of land plants called Class III HD-Zip genes. They found that these genes were controlled by microRNAs and that the microRNA binding region was almost identical in moss, club moss, liverworts, ferns, Douglas fir, Mexican yew and Arabidopsis. Not only were the amino acid sequences of the proteins highly conserved, but also the nucleotide sequence of the microRNA binding site in the mRNA had been conserved for 400 million years. This was the first demonstration of gene regulation by a microRNA in non-flowering plants such as mosses and ferns. , 5 April 2004

New hereditary gene linked to Parkinsons disease

Scientists led by Professor Nick Wood at University College London, the United Kingdom, have discovered a new gene implicated in the early development of Parkinsons disease. In a study of families with early onset disease, they identified a novel gene, which produces a malfunctioning protein that could pave the way for new treatments for Parkinson sufferers.

The international study, which involved 14 research centres, mapped the genes in one Spanish and two Italian families where cousins had married and produced offspring. The researchers traced the chromosome location of the gene responsible for this form of familial Parkinsons disease and were able to pinpoint mutations in the gene of the affected families. The mutations in PTEN-induced kinase 1, or PINK1, led to a dysfunction of the protein, which in turn reduced the ability of brain cells to protect themselves from stress.

The discovery of this gene has revealed a completely novel and hitherto unconsidered pathway, which could open the way to identifying new forms of therapeutic treatment. The finding has also placed mitochondrial function at the centre of research into Parkinsons disease and potentially other neurodegenerative diseases like Alzheimers. , 16 April 2004

Genetic trick adapted from viruses makes versatile vectors

Dr. Dario Vignali and his co-researchers at the St. Jude Childrens Research Hospital, Tennessee, the United States, have found that the genetic trick used by viruses to replicate themselves could be used to develop gene therapy vectors in cases when cells must be modified to make high levels of different proteins. The achievement would give researchers a powerful tool for studying the roles of complex proteins in living cells. The technique would permit scientists either to restore complex protein structures that are missing in certain cells or make multiple proteins that act together as potent drugs against cancer and other diseases.

The technique is based on a genetic trick, called a self-cleaving 2A peptide, which is used by some viruses to produce multiple proteins from a single length of DNA. The researchers used genetically modified mouse T cells to test the efficiency of the technique in making the CD3 complex, which is part of the T cell receptor. The receptor allows T cells to sense targets that the cells are programmed to destroy; the T cell receptor is incomplete and cannot operate without the CD3 complex.

The researchers inserted into the retroviral vectors cassettes (groups of genes) that contained genes for the four CD3 proteins, separated by the 2A peptides. These 2A peptides acted like cleavers to break apart the long protein into the four different, similar CD3 proteins. The multicistronic retroviral vectors were then used to deliver the 2A peptide-linked CD3 gene cassettes into hematopoietic stem cells from mice that lacked the CD3 proteins, and thus could not make T cells. These genetically modified stem cells used the smaller CD3 proteins to build large TCR:CD3 receptor and subsequently restored T cell development in mice. According to Dr. Vignali, these 2A peptides would allow researchers to generate single vectors that could efficiently and reliably express multiple proteins in the exact amounts needed to permit the cell to assemble complex structures.

(Express Pharma Pulse, 15 April 2004)

Gene-rich human chromosome 19 sequence completed

Scientists at the United States Department of Energys Joint Genome Institute (JGI) and the Stanford University, both based in California, have successfully sequenced human chromosome 19, the most gene-rich of all the human chromosomes.

The team of scientists selected chromosome 19 as a sequencing target to investigate the link between DNA damage from radiation exposure and human cancer. The sequencing revealed that chromosome 19, at 55.8 million bases or letters of genetic code, represented only about 2 per cent of the human genome but featured nearly 1,500 genes. They included genes that code for such diseases as insulin-dependent diabetes, myotonic dystrophy, migraines and familial hypercholesterolemia. Beyond the significant revelation that chromosome 19 has more than twice the gene density of the genome-wide average, it also offered a fertile landscape for exploring evolutionary motifs. Chromosome 19 has a highly repetitive sequence and a high GC content. An intriguing picture emerged, revealing large blocks of gene conservation with rodents as well as segments of coding and non-coding conservation with more distant species such as the pufferfish, Fugu rubripes, which was also sequenced at the JGI.

Unlike earlier draft human genome sequences, the version of chromosome 19 was 500 times better in terms of contiguity and accuracy. The quality of the finished chromosome 19 sequence far exceeded the 1 in 10,000 base pair error rate set by the International Human Genome Sequencing Consortium; the error rate was estimated to be much less than 1 in 100,000 base pairs. Embedded in this sequence information was critical regulatory networks of genes tasked with controlling such functions as repairing DNA damage from exposure to radiation and to other environmental pollutants. With this high-quality sequence now made freely available to the scientific community, more light would be shed on individual responses to medicines. This would enable the development of more sensitive diagnostics for susceptibility to a wide array of important diseases. This would help in tailoring more effective individualized therapeutic strategies. , 31 March 2004

Research describes genes active in human embryonic stem cells

Research conducted by Dr. Ralph Brandenberger and colleagues at Geron Corporation, California, the United States, has identified genes active in human embryonic stem cells (hESCs) and in hESCs undergoing differentiation. The work, which was performed under Gerons prior collaboration with Celera Genomics Group in Maryland, has elucidated signalling pathways operative in hESCs that likely play key roles in their growth and differentiation. This would facilitate derivation of useful differentiated cell types for therapy, and might also lead to the development of novel tools for drug discovery.

As part of their collaboration, Geron and Celera produced cDNA libraries from undifferentiated hESCs and three partially differentiated progeny cell populations. The over 148,000 physical clones sequenced represent more than 32,000 transcripts, expressed genes in the human genome. These data were analysed to identify over 600 genes preferentially upregulated or downregulated in undifferentiated hESCs and to assemble a blueprint of molecular pathways functional in hESC differentiation.

According to Dr. Brandenberger, the research represented a unique large-scale comparison of genes expressed in undifferentiated hESCs and their differentiated progeny. This approach allowed fine discrimination of gene expression patterns between directly related cell types, thus permitting identification of genes likely to be important in the maintenance of undifferentiated hESCs and in the transition to the early differentiated state. Controlling the growth and differentiation of hESCs could be used as the key to developing well-characterized cell populations for therapeutic use.

Bioresearch Online, 17 May 2004


Stem cells may lead to baldness cure

Dr. George Cotsarelis and his co-researchers at the University of Pennsylvania, Philadelphia, the United States, have shown that bald mice could grow hair after being implanted with a type of stem cell. The study could lead to a cure for baldness. The project marked the first time that blank slate stem cells were able to induce hair growth. These cells had the ability to generate hair when taken from one animal and put into another.

The study suggested that the existing stem cells could be isolated using isolation processes and reimplanted them in the areas where people were bald. The study confirmed that hair follicles contained blank slate stem cells that gave most humans a full head of hair for life. Although they were called stem cells, they differed from embryonic stem cells. The biologists studying regenerative qualities of hair, however, cautioned that a baldness cure was still years away.

Chronicle Pharmabiz, 18 March 2004

GM bacteria used to fight cancer

Scientists led by Dr. Georges Vassaux of Cancer Research Molecular Oncology Unit at London, the United Kingdom, and the London Queen Marys School of Medicine and Dentistry used a genetically altered version of the food poisoning bug E. coli to deliver a cancer-killing enzyme directly into the cells.

Tests using E. coli showed that over 90 per cent of cancer cells were destroyed. The bacteria were made to carry an enzyme called purine nucleoside phosphorylase into cancer cells. The enzyme works in conjunction with a powerful anti-cancer drug called 6-MPDR, which cannot be activated until the enzyme is inside the cancer cells. When researchers targeted mouse tumours with the bacteria-drug combination, it appeared to slow down tumour growth and cause large numbers of cancer cells to die. The researchers used a version of E. coli that had been modified so that it could no longer grow, divide or cause disease. They added a gene called invasin to give E. coli he power to enter human cells by passing through their outside membranes, which it cannot normally do. They also added a second gene, called listeriolysin O, which instructs the E. coli to release the enzyme it is carrying once it is inside the cancer cell. With a few important genetic modifications, the bacteria were turned into efficient delivery capsules, able to penetrate the outside membrane of cancer cells and protecting purine nucleoside phosphorylase until it is safely inside. This has provided the scientists with a method of breaking through previously impenetrable barriers around the cells.

The therapy might also attack cancer cells in a second way. Introducing neutered bacteria into a patients body, though harmless, would provoke the immune system and help to direct it against the tumour. According to Dr. Vassaux, using bacteria to treat tumours is an innovative new therapy to deliver treatments to cancer cells and might offer the potential to target cancer cells with a range of different therapeutic molecules. , 22 April 2004

Scientists create mice with human immune systems

At the Institute for Research in Biomedicine, Bellinzona, Switzerland, a team of scientists led by Dr. Markus G. Manz has created mice with human immune systems, making it possible to study diseases that attack humans, without using people as subjects. The researchers took blood stem cells from human umbilical cord and transplanted them into infant mice that didnt have their own immune systems. The transplanted cells created many types of human immune system cells including T-lymphocytes, B-lymphocytes and dendritic cells. Moreover, Dr. Manzs team found that these human immune cells worked along with the mouses own cells to make lymph system organ structures, a major component of the bodys immune system, and to produce regular immune responses.

The humanized mouse model could provide a valuable tool to study pathogens that specifically target the human immune system and test potential therapeutic interventions. Further development could make it very useful in analysing the human immune system, including how the system develops, its function and its response to infectious agents such as Epstein-Barr virus and HIV. Moreover, the model could prove useful for vaccine development and for studying therapies against a whole range of pathogens for which no animal model exists. , 1 April 2004

Immune cells grown in a dish

Dr. Juan Carlos Ziga-Pflcker and colleagues at the University of Toronto, Ontario, Canada, have grown potentially limitless T cells in the laboratory in an experiment that would help boost therapy for cancer and HIV. The T cells were made from mouse embryonic stem cells, which normally form all the tissues in a mouse embryo. The scientists started by identifying a molecule, called DL1 that was essential in T cell production. They genetically engineered cells to make DL1, and then grew embryonic stem cells on top of this concoction. The DL1 stimulated the stem cells to make immature immune cells and when these cells were implanted into mice lacking an immune system, they in turn made mature T cells, helping the mice fight off a mild viral infection.

Scientists hope that T cells grown from human embryonic stem cells might one day be used in cancer and HIV patients whose own supply had been wiped out. HIV patients could be given cells genetically enhanced to fight the virus. The technique would work best if the immature immune cells could be delivered into the thymus. Further, the lab-made immune cells could be used for any patient, because they lacked surface molecules that trigger rejection. And because embryonic stem cells keep dividing indefinitely, they might sprout an unlimited supply. The new technique could also help in knowing how T cells develop and function. , 22 March 2004

Engineered virus provides impetus in search for HIV vaccine

A team of scientists led by Dr. Michael Barry at Baylor College of Medicine, Texas, the United States, has engineered a hybrid gene therapy vector that contains components of two viruses. This vector could provide a vehicle for producing a vaccine against a host of diseases, including the human immunodeficiency virus. The vector uses potent features of adenovirus that normally infects respiratory tissues and of reovirus that infects the mucosal membranes of the gut. To develop this potential vaccine vector, a key protein of reovirus that allows it to enter the gut was exchanged into adenovirus to retarget this non-infectious gene therapy vector into mucosal surfaces. According to Dr. Barry, mucosal targeting vector might prove quite potent for repelling viruses like HIV-1 and infectious bioweapons, since most pathogens enter the body at mucosal surfaces. It would be first tested as an HIV vaccine in mice and if found successful, it might be useful for a wide variety of other pathogens.

This hybrid vector would also be useful in studying the specific interactions of this reovirus protein in the host. This was difficult earlier owing to the complex genetics of reovirus. These complex interactions could now be studied using the simpler genetic system provided by the adenoviral vector. , 15 April 2004

Crohns disease gene isolated

At University of Toronto, Ontario, Canada, a team of researchers led by Dr. Katherine Siminovitch has isolated a gene that predisposes people to Crohns disease. This was a critical step towards improved diagnosis of the disease and developing better therapies for Crohns disease, an inflammatory bowel disease whose existing treatments are considered unsatisfactory. Using DNA samples from family groups, Dr. Siminovitch and her team employed a technique called positional cloning to first locate the chromosome containing the gene and then identify the gene. The gene isolated by the researchers produced a protein that sat on the cell surface and regulated how substances enter and exit the cell. In a majority of Crohns disease patients, this protein functioned improperly and allowed toxins easier access to the cell.

The ability to test for this protein malfunction would help doctors distinguish between Crohns disease and ulcerative colitis, the other major form of inflammatory bowel disease known. This information could also be used to diagnose Crohns disease at an earlier stage and to develop new approaches to treatment. The findings should shed additional light on the basic causes of chronic inflammation, which also lead to rheumatoid arthritis besides Crohns disease. The team of researchers is now working on the development of a chemical that would alter the protein to restore its normal function. , 12 April 2004

Gene therapy restores function of damaged heart cells in lab

In the United States, Dr. Walter Koch at Jefferson Medical College of Thomas Jefferson University, Philadelphia, and his co-workers at Duke University Medical Centre, North Carolina, successfully employed gene therapy in the laboratory to help damaged heart cells regain strength and beat normally again. The scientists used a virus to carry a gene into the heart cells of individuals who had suffered from congestive heart failure. The gene introduced into these heart cells blocked the activity of an enzyme that was increased in failing human hearts and which contributed to the loss of the hearts contractile strength during the development of heart failure. When the activity of this enzyme was blocked by gene therapy, the heart cells were able to contract at normal strength and their overall performance improved.

It was known to the researchers that the beta-adrenergic receptor system (which drives the heart) fails to work properly in individuals with congestive heart failure. Dr. Kochs team targeted beta-adrenergic kinase (ARK1), an enzyme that gets elevated in human heart failure. One of the functions of the enzyme is to switch off the beta-adrenergic receptors, causing dysfunctional beta receptor signalling. A failing heart then has little capacity to respond to exercise or stress because there are fewer receptors and the remaining receptors are more or less turned off. In the laboratory dish, the researchers infected heart cells from patients who underwent cardiac transplantation owing to end-stage heart failure with an adenovirus (a common cold virus that had been rendered non-infectious) that encoded both ARKct a peptide that could block ARK and a so-called reporter gene protein, which glowed green. The latter provided a signal to the scientists that the inhibitor was indeed present in the heart cells. They then used a video camera to measure how strong the individual heart cells were beating.

According to Dr. Koch, this was the first work in actual human hearts to show efficacy of ARKct as a potential therapy and more importantly, it proved that the enzyme ARK1 was a target for heart failure treatment. This work would eventually lead to clinical trials in human. , 6 April 2004


Bumper compendium of human genes released

A group of 152 researchers from 11 countries, known as the H-Invitational international consortium led by Dr. Takashi Gojobori at the Japan Biological Information Research Centre, Tokyo, Japan, has published a detailed compendium of about two-thirds of all human genes. The database links 21,037 validated genes to a huge amount of biological data and has been hailed as a major step forward for medical and biological science. It contains a large part of information about the functions of the roughly 30,000 genes of the human genome.

Users of the consortiums website would soon be able to explore each genes structure and the alternative ways it could generate RNA messages. They would also be able to assess the predicted 3-D structures of the proteins encoded by the genes and their cellular location. Another analysis made possible by the database was the gene difference between individuals, as compared with mouse genes.

The team expects the freely accessible database to boost efforts to hunt down the genetic triggers of many diseases. Pharmaceutical researchers are also expected to make use of the resource. , 20 April 2004

Strand-Interfocus agreement for European market

Strand Genomics in Bangalore, India, has announced its distribution agreement with Interfocus in Suffolk, the United Kingdom, to sell Avadis, Strands flagship product for microarray data analysis and visualization. Interfocus would represent Avadis in Austria, France, Germany, the United Kingdom and Switzerland.

Avadis brings the very best in data mining techniques and the finest in software engineering to microarray gene expression analysis. It combines deep scalable analysis algorithms with a powerful visualization engine and the ability to access data and annotations. The uniqueness of Avadis stems from its depth in all the three dimensions that facilitate discovery access, visualization and analysis. It is a solution that meets all the needs of gene expression researchers with a superior performance-to-price feature, and is available in three editions explorer, prophetic and pride.

Being well established in Europe, Interfocus would help Avadis penetrate the European market and gain a significant market share. Sales Director of Interfocus, Mr. Marcus Cannon, feels that in a very competitive market, Avadis would offer value and would be an important driving force in Europe.

Chemical Weekly, 13 April 2004

First genome-scale computational model of gene regulation

Bioengineers led by Prof. Bernhard Palsson at the University of California San Diego (UCSD), the United States, has produced the first genome-scale computational model of the gene regulatory system in E. coli. The model would help define the rules that govern cell function and quickly enable an exponential increase in the understanding of the regulatory system in E. coli.

According to Prof. Palsson, the research was evidence of how much more quickly biological discovery would progress now, given that high-throughput experimental tools for gathering large volumes of data are available and the use of these tools could be guided by computer models. The work demonstrated that a cellular regulatory system could be reverse-engineered at the genome scale, and the model could then be used to systematically gain new knowledge about how the cell functioned. The UCSD model included a network for 1,010 genes, including 104 regulatory genes, whose products together with other molecules regulated the expression of 479 of the 906 genes known to be involved in cellular metabolism.

The team conducted a series of experiments focused on E. colis response to oxygen deprivation and made predictions of cellular behaviour through simulations with the previous in-silico model. These predictions guided high-throughput data-gathering experiments using gene chip technology. In the laboratory, the team created strains of E. coli in which genes involved in oxygen regulation were deleted, and then subjected the strains to experiments both with and without oxygen. When the predicted outcomes did not match the experimental outcomes, the experimental data were used to update the in-silico model. Through this process, the team uncovered new details about how E. coli responded to oxygen deprivation and identified 115 previously unknown regulatory mechanisms.

They also identified new regulatory interactions for genes that no one had previously described, basically opening up a whole new research area in terms of characterizing regulatory networks in E. coli. Another observation by the team was that the microbes regulatory network was much more complex than was expected for such a relatively simple single-cell microbe. That meant that the lessons learned through the E. coli modelling process would help scientists model much more advanced organisms such as mice and even humans. , 5 May 2004

Indian Bioinformatics Society to certify professionals

The Government of India plans to constitute Indian Bioinformatics Society (IBS) with a mandate to certify the quality of human resources in bioinformatics through a national-level eligibility test. The formation of the IBS has been recommended by the national coordinators of the Biotechnology Information System (BTIS) programme of Department of Biotechnology (DBT). A national system of recognition of trained bioinformatics personnel would help optimal utilization of human resources available in the emerging sector of bioinformatics. IBS would be asked to take the responsibility of sharing the human resource within the bioinformatics society. It would also take a lead role in conducting multi-centric research and educational activities in bioinformatics.

BTISnet comprising an Apex Centre at the DBT, 10 specialized Distributed Information Centres (DICs) in identified major areas of biotechnology and 50 Distributed Information Sub-Centres (Sub-DICs) would play a pivotal role in the materialization of IBS. The government recognized certification is expected to streamline the functioning of private bioinformatics institutions in the country. The certification, an indirect way of ascertaining the quality of training imparted by the institutions, is expected to help increase the standards of bioinformatics education and services offered by them.

Chronicle Pharmabiz, 13 May 2004


Self-assembling proteins to help repair human tissue

A team of researchers led by Dr. James L Harden at Johns Hopkins University, Maryland, the United States, has created a new class of artificial proteins that could assemble themselves into a gel and encourage the growth of selected cell types. This biomaterial, which could be tailored to send different biological signals to cells, would help those who are developing new ways to repair injured or diseased body parts.

According to Dr. Harden, this would be an important new tool for tissue engineers to help them do their work more quickly and efficiently. Tissue engineers use hydrogels (macromolecular networks immersed in an aqueous environment) to provide a framework or scaffold upon which to grow cells. The team at Johns Hopkins is the first to produce a self-assembling protein gel that could present several different biological signals to stimulate the growth of cells. The scientists hope to advance their techniques to be able to treat medical ailments by growing replacement cartilage, bones, organs and other tissue in the lab or within a human body.

Express Pharma Pulse, 8 April 2004

Action mechanism of RNA helicase enzymes redefined

A team of scientists led by Dr. Eckhard Jankowsky at the Case Western Reserve University School of Medicine, Ohio, the United States, has provided new insight into the function of RNA helicases, also called DExH/D-RNA helicases. They have found direct evidence that these enzymes could utilize energy gained from hydrolysis of ATP to change shape and composition of RNA-protein complexes without unwinding RNA duplexes. It was earlier assumed that these enzymes used energy stored in APT molecules to exclusively unwind double-stranded RNA.

The team showed that two different RNA helicases could displace proteins from single-stranded RNA and that duplexes were not necessarily disrupted by the enzymes during their biological functions. The findings essentially redefined the mechanism of action of RNA helicases and constituted a paradigm shift in assessing roles of these enzymes in virtually all biological processes that involved RNA.  6 May 2004

Scientists create 22-amino acid bacterium

Reasearchers at The Scripps Research Institute and its Skaggs Institute for Chemical Biology, La Jolla, California, the United States, have modified Escherichia coli to use a 22-amino acid genetic code. They engineered this modified form of E. coli to make myoglobin proteins with 22 amino acids incorporating the unnatural amino acids O-methyl-L-tyrosine and L-homoglutamine in addition to the naturally occurring 20. The scientists have thus demonstrated the simultaneous incorporation of two unnatural amino acids into the same polypeptide. The research is a boon, as it proves that multiple unnatural amino acids could be added to the genetic code of a single modified organism. This could open the door for making proteins within the context of living cells with three, four, or more additional amino acids at once.

The research team succeeded in making the 22-amino acid E. coli by exploiting the redundancy of the genetic code. Several of the 64 codons are redundant, coding for the same amino acid, and three of them are nonsense codons they do not code for any amino acid at all. One of these, the amber stop codon UAG, played an important role in the research. The team knew that if it could provide the cells with a tRNA molecule that recognized UAG and a synthetase loading enzyme that loaded this tRNA with an unnatural amino acid, there would be a way to site-specifically insert the unusual amino acid into any protein.

Starting with a tRNA/synthetase pair from the organism Methanococcus jannaschii, the scientists created a library of E. coli cells, each encoding a mutant M. jannaschi synthetase, and changed its specificity so that it could be used to recognize the unnatural amino acid O-methyl-L-tyrosine. To do this, they devised a positive selection whereby only the cells that loaded the orthogonal tRNA with any amino acid would survive. Then they designed a negative selection whereby any cell that recognized UAG using a tRNA loaded with anything other than O-methyl-L-tyrosine dies. In so doing, they found their synthetase mutants loaded the tRNA with only the desired unnatural amino acid. When a ribosome reading an mRNA within the E. coli cells encountered UAG, it inserted the unnatural amino acid O-methyl-L-tyrosine. Furthermore, any codon in an mRNA that was switched to UAG encoded for the new amino acid in that place, giving the team of scientists a way to site-specifically incorporate novel amino acids into proteins expressed by E. coli.

Similarly, the scientists made an engineered tRNA/synthetase orthogonal pair from the polar archean organism Pyrococcus horikoshii that recognized the four-base codon AGGA. This led to incorporation of unnatural amino acid L-homoglutamine in the polypeptide. By placing both these systems within the same E. coli cell, the scientists proved the principle that it was technically possible to have mutually orthogonal systems operating at once in the same cell. , 11 May 2004

Anti-aging enzyme target found

Dr. Ronen Marmorstein and his colleagues at The Wistar Institute, Philadelphia, the United States, have discovered the activation of key anti-aging enzyme. They revealed the workings of a family of enzymes called sirtuins that were critical to such processes as metabolism, aging and cancer development. The discovery could lead to formulation of a drug that flipped on longevity switches, and potential interventions that might boost the activity of the sirtuin Sir2, which had previously been linked to life extension in yeast and worms.

According to Dr. Marmorstein, Sir2 sirtuin silenced gene expression and stabilized the genome in yeast. Sirtuins were highly conserved in humans. The research team was exploring the idea that if sirtuins could be activated, genomic stability could be promoted and cancer as well as other aging-related problems could be decreased. The team focused on the molecular details of how sirtuins worked, using a yeast sirtuin as a model and captured three dimensional images of it to gain a structural picture of its enzymatic activity. This led the team to a binding site, which activated the sirtuin when blocked. Using virtual libraries of molecules, researchers are now identifying molecules with structures that might bind to that site and serve as Sir2 activators. , 17 May 2004


Oil-rich GM plant may ease pressure on fish stocks

Plant biologists led by Dr. Baoxiu Qi and Dr. Colin Lazarus at Bristol University, Bristol, the United Kigdom, have developed a genetically modified plant that produces all the healthy fats found in oily fish. The weedy type of cress was modified as an alternative source of polyunsaturated fats known as omega-3 and omega-6 fatty acids, out of which omega-3 is abundant in certain fish. The cress was modified with genes taken from three different micro-organisms and its production of the fats indicated that it could be used as a viable alternative source of healthy fats.

The potential benefits of genetically modified oil-rich cress include its use to help reduce heart disease and improve brain function and mood. The use of modified plants would take the pressure off severely depleted fish stocks. Oils made from the plants were also likely to be more pure than many fish oil supplements. People with diets lacking in the fats from fish might stand to benefit. These plants could also be turned into animal feed. , 17 May 2004

GM corn cuts carbohydrates

Dr. Daniel Gallie and his colleagues at University of California, Riverside, the United States, have created a genetically engineered breed of corn with half the usual amount of carbohydrates but double the fat and protein. The teams main hope is that the GM corn would supplement protein-deficient diets in many parts of the world. It might also prove a boon to farmers who want such high-energy corn for their pigs and chickens. Dr. Gallie and his team studied corn flowers, which came in pairs called florets. Normally, only one floret in each pair is pollinated and that survives to make a corn kernel. Inside each kernel is an embryo rich in protein and oils, which would sprout a new seedling, and a carbohydrate-rich endosperm that nourishes it.

The team genetically engineered corn plants so that the flowers produced a hormone that enabled both florets to survive and to be pollinated. The resulting corn kernels contained two embryos and a smaller, squashed endosperm. As a result, the corn packed double the normal amount of protein and fat but only half the carbohydrate.

According to Dr. Gallie, the low-carbohydrate trait might be bred into other strains of corn, and many companies were interested in developing the crop. If the prototype corn was grown commercially, it could find a market among the crowd following low-carbohydrate diets. But like any genetically engineered crop, it would have to clear regulatory and ethical hurdles before it could be sown. , 11 May 2004

Brazil maps Arabica coffee genome to improve quality

Genome mapping of Arabica variety of coffee was successfully completed by scientists led by Dr. Alan Carvalho Andrade at the Brazilian governments agricultural research agency, Embrapa. So Paulos research foundation, Fapesp, helped coordinate the coffee genome project, which cost US$2.05 million and was funded by the National Coffee Development Fund of Brazil.

The project sequenced 200,000 nucleotides found on 11 chromosomes containing 35,000 genes. These formed the blueprint for the beverages taste, texture, flavour and other qualities. The aim of the project was to improve quality and yields by protecting coffee against disease and vagaries of weather.

According to Andrade, it was uncertain how long it would take to start commercial production of improved coffee varieties. However, researchers had estimated that cost savings of 50-100 per cent could be made on herbicides, pesticides and other crop chemicals, and that productivity could be raised by 30-50 per cent. , 20 April 2004


Computational Genomics: Theory and Application

Written by leading international experts, this comprehensive book details the application of current computational methods to protein science and DNA. Among the topics covered are: database search, sequence analysis and comparison, multiple sequence analysis, large-scale EST analysis, genome browsing, protein structure prediction, microarray data analysis and proteomics. Topics are covered with a practical approach that enables biologists to perform analyses and comparisons of sequence data and to determine functional and structural characteristics of proteins. In particular the book aims to provide an understanding of the ways in which such analyses and comparisons are performed. Suitable for bioscientists who are just getting to grips with computational biology, the book also offers enough detail to act as a guide for experienced bioinformaticians at the cutting edge of the technology.

Protein Expression Technologies: Current Status and Future Trends

Advances in protein expression technologies have mushroomed in recent years. In this book, internationally renowned authors have reviewed current and emerging expression technologies. Detailed reviews of the molecular genetics of expression systems in various organisms are presented. Topics covered include: expression of extremophilic proteins; expression in E. coli, Bacillus spp., Saccharomyces cerevisiae and methylotrophic yeasts; insect cell expression and the baculovirus system; and Chinese Hamster Ovary cell lines for large-scale protein production. Two emerging expression systems Methylobacterium extorquens AM1 and Caulobacter crescentus are also coverd in this essential reference book.

Contact: Horizon Scientific Press, Rowan House, 28 Queens Road, Hethersett, Norwich NR9 3DB, United Kingdom. Tel: +44 (1953) 601106; Fax: +44 (1953) 603068.


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