VATIS Update Biotechnology . Jan-Feb 2007

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Biotechnology Jan-Feb 2007

ISSN: 0971-5622

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

Co-publisher: Biotech Consortium India Ltd
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Centre of Excellence in Genomics being set up in India

The International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) and the Department of Biotechnology (DBT), Government of India, are joining hands to establish a Centre of Excellence in Genomics (CEG) at ICRISAT. A Memorandum of Agreement on the Centre was signed recently by Dr. William Dar, Director General of ICRISAT, and Dr. M.K. Bhan, Secretary of DBT. The project would help alleviate the poverty of smallholder farmers in the dry land areas of India and rest of world. The CEG would provide new technological options, build capacity of scientists and also accelerate crop improvement by halving the time required to develop new varieties.

The facility, which is expected to be fully operational over the course of 2007, would be available for researchers from other agricultural research institutes. The CEG would provide: facilities for high-throughput, low-cost, allele detection platforms to help with molecular marker-assisted selection and breeding; access to large-scale field screening for abiotic stresses such as drought and salinity; biometrics and bioinformatics support; and fellowships and training courses for scientists and students from the Indian institutes in the use of high throughput methods in breeding and research. The partnership is significant since it links international research and national research.


Brazilian gene bank becomes worlds seventh largest

A Brazilian gene bank of plant seeds has become the worlds seventh largest, behind those in the United States, China, Germany, Japan, India and the Republic of Korea. Gene banks store genetic material from plants or animals such as seeds, spores or eggs frozen in cold chambers at -20C, preserving it for over 100 years for later use. The number of seed samples stored in the gene bank managed by the Brazilian Agricultural Research Corporation reached 102,000 representing genetic material collected from 500 different plant species.

The seeds provide a wide range of genes that could be used to develop more suitable crops for every Brazilian region. With genetic improvement, it is possible to originate plants with resistance to diseases or to dryness. Gene banks can also help prevent species extinction; if the seeds are stored, plants that no longer sprout naturally can be reintegrated into agriculture.

New seeds are constantly added to the bank from international exchanges and field collections and regular tests evaluate their germination ability. The Agriculture Research Service of the United States Department of Agriculture manages the worlds largest seed bank, which holds more than 460,000 seed samples and has the capacity to store up to 1 million.


South Africa to host international genetics lab

South Africa would be the first country in Africa and the third in the world to host a laboratory of the International Centre for Genetic Engineering and Biotechnology (ICGEB), at the University of Cape Towns Institute for Infectious Diseases and Molecular Medicine.

Better disease control and management of crops are some of the issues that would be tackled by the new laboratory. The research would contribute to global efforts to stop and reverse the spread of HIV and AIDS, malaria and other diseases by 2015.

ICGEB is an international organization dedicated to advanced research and training in molecular biology and biotechnology with special regard to the needs of the developing world. Its primary focus in the field of biotechnology is on HIV and AIDS, hepatitis, rotavirus, human papilloma virus, malaria and tuberculosis. The other two ICGEB laboratories are in Italy and India.


Biotech industry sets out new policy agenda for Europe

The European biotechnology industry has published a new Industrial Biotechnology Policy Agenda for Europe, setting out a range of proposals that could see the industrial biotech sector form the basis of a future knowledge-based bio-economy (KBBE) in the European Union. The report was produced by EuropaBio, the European Association for Bio-industries and endorsed by the European Federation of Biotechnology section on Applied Biocatalysts (ESAB).

Industrial biotechnology, also known as white biotechnology, involves the use of enzymes, micro-organisms and plants to make products in a range of industrial sectors such as pharmaceuticals, chemicals, food and feed, paper and pulp, energy, textiles, materials and polymers.

EuropaBio describes KBBE as, Where biotechnologys new, clean, energy-efficient processes and innovative bio-based products create a sustainable industrial base to ensure Europes future prosperity. The report states that there is a great need to harmonise the various policy areas that involve biotechnology, such as research, climate change, sustainable development and reform of the Common Agricultural Policy.


Vatican welcomes new stem cell advance

The city state of Vatican welcomed a new way of extracting stem cells that does not use human embryos, calling it a significant advance that could help medical research without going against the beliefs of Roman Catholics. According to Cardinal Javier Lozano Barragan, Head of the Vaticans Pontifical Council for Health Pastoral Care, the discovery showed medicine could progress without destroying human embryos. The Vatican also revealed that the church was not opposed to stem cell research and was always ready to welcome real scientific progress that neither threatens nor manipulates the sources of life.

The Catholic Church and other religious groups have been staunch critics of the most common method of stem cell research, which involved extracting cells from human embryos, because they believed it to be against the laws of nature when considering these organs are human beings.

The latest announcement is based on the report from United States researchers that stem cells found in the amniotic fluid protecting babies in the womb are nearly as powerful as embryonic stem cells in producing adaptable cells that can transform medicine.


Five new stem cell centres to be established in India

Life Cell, India, a stem cell banking company is opening its five new centres in addition to the 26 centres already existing at different cities in India and is also expecting the total number of stem cell centres would move up to 50 by the end of 2008.

Cord blood stem cells have the potential to cure over 75 diseases and stem cell therapy had been prominently used in treating various diseases like leukaemia, thalassemia, anaemia and other blood disorders. Stem cell therapy could be the most promising solution for conditions like thalassemia, which is widely prevalent in the Middle East.

Life Cell will soon set up its stem cell transplant centre in Chennai in collaboration with Sri Ramachandra Medical College and Research Institute (SRMC). The centre is specialized in the field of haematology. Life Cell also has a technology tie-up with Cryo-Cell International (CCI) USA, who are pioneers in the field of cord blood banking and is the worlds biggest cord blood bank.


Biotech plays critical role in New Zealand economy

Biotechnology continues to play a critical part in New Zealands economy, contributing US$200- 270 million each year, says the New Zealand Biotechnology Industry Growth Report. The report by LEK Consulting was commissioned by the Ministry of Research, Science & Technology, New Zealand Trade and Enterprise and NZBio, New Zealands national biotechnology industry body.

Key findings show expenditure on biotechnology increased by 20 per cent to US$445 million during the period 2004-05, with biotechnology export revenue increasing by 30 per cent over the same period. The biotechnology industry now employs more than 2,200 people in New Zealand. While the countrys natural strengths in primary industries, forestry and horticulture shine through, the country has a balanced biotechnology portfolio with an increasing focus on medical devices and diagnostics, human health applications and industrial biotechnology.



Luminex to acquire Tm Bioscience

Luminex Corporation, the Unites States, and Tm Bioscience Corporation, Canada, have announced a definitive agreement for Luminex to acquire Tm Bioscience. Tm Bioscience is a leading DNA-based diagnostics company developing a suite of molecular diagnostic tests. Its products include tests for infectious diseases and for genetic mutations related to cystic fibrosis, sepsis and other debilitating genetic disorders. It has proprietary technologies that improve the accuracy, flexibility, speed and cost of DNA-based genetic tests. The cystic fibrosis test is the first multiplexed human disease genotyping test from Tm Bioscience to be cleared by the United States Food and Drug Administration for diagnostic use in that country.

Luminex Corporation develops, manufactures and markets proprietary biological testing technologies with applications across the life sciences industry. The companys xMAP system is an open architecture, multi-analyte technology platform that delivers fast, accurate and cost-effective bioassay results to markets as diverse as clinical diagnostics, pharmaceutical drug discovery, and biomedical research, including the genomics and proteomics research markets.


New company for genetic research in the United Kingdom

A specialist agency London Genetics has been launched to facilitate partnerships between industry and academic centres of excellence in genetics- and genomics-based research across London, the United Kingdom. It is formed by a consortium of leading London universities and research institutes, and funded by the London Development Agency. It will be the first stop for anyone looking to conduct basic research, translational research or clinical studies in London, and to expedite the translation of genetics- or genomics-based research into clinical benefits demonstrating the commercial value of genetics.

A key strength of London Genetics would be its ability to commission multi-centre studies through its partners. Using its specialist subject knowledge and extensive networks, the company can meet accurately the needs of its customers in areas such as: translational research; access to large, well-characterized, clinical cohorts; DNA diagnostics; pharmacogenetics; and high throughput genomics. In addition, it has access to cutting edge technologies, research methods and expertise in bioinformatics, data handling and analysis.


Raven signs agreement with Wyeth Pharma to develop MAbs

In the United States, Raven Biotechnologies Inc., focused on the development of monoclonal antibody (MAb) therapeutics for treating cancer, has entered into an agreement with Wyeth Pharmaceuticals to develop and commercialize selected MAbs from Ravens portfolio of antibodies to a specified target.

The agreement gives Wyeth Pharmaceuticals, a division of Wyeth, the option to obtain an exclusive licence to develop and commercialize therapies arising from the use of these designated Raven MAbs. The antibodies included in the agreement were discovered using Raven proprietary immunization technology and tumour-derived stem cell lines, and were screened to select antibodies that are active alone or in a conjugated form. Raven proprietary antibody discovery processes rapidly create monoclonal antibodies and allow researchers to quickly assess the importance of those proteins in the disease process.


CyGenics to collaborate with Zhejiang Province blood centre

CyGenics Ltd, Australia, signed an agreement with the blood centre of Zhejiang Province (ZBC) in China for work on generating human T-cells outside the body for the treatment of HIV, using the cellular growth technology of CyGenics. The patented three-dimensional growth scaffold of CyGenics, called Cytomatrix, had been shown in laboratory studies as having the ability to generate T-cells to become an artificial thymus.
ZBC has ready access to all sources of haematopoietic stem cells such as umbilical cord blood, bone marrow and peripheral blood. It would use stem cells donated for research to undertake a series of studies. Once the studies are completed, ZBC might assess the feasibility of applying the technology for the treatment of HIV subject to regulatory approval.


Ablynx, Boehringer to jointly discover Alzheimers treatments

Boehringer Ingelheim of Germany and Ablynx of Belgium have jointly announced a worldwide collaboration and licensing agreement worth US$ 265 million to discover and develop new therapies for Alzheimers disease using Ablynxs Nanobodies. Ablynx is a biopharmaceutical company engaged in the discovery and development of Nanobodies, a novel class of therapeutic proteins based on single domain antibody fragments, for a range of serious and life-threatening human diseases.

Nanobody-based therapeutics represent a major commercial opportunity, since they combine the beneficial features of conventional antibodies with desirable properties of small-molecule drugs. Because they are derived from naturally occurring heavy-chain antibodies, Nanobodies have unparalleled stability.

Nanobodies may cross the blood-brain barrier more readily than conventional antibodies owing to their special characteristics. They are able to overcome the delivery issues associated with full-sized antibodies, that can only be delivered by injection, and can be administered in a variety of ways such as injected, oral, or in sprays or creams. Nanobodies manufactured in micro-organisms also has a significant cost advantage when compared with production methods for conventional antibodies.


Invitrogen and Blue Heron enter into strategic relationship

In the United States, Invitrogen Corporation, a global leader in life sciences, and Blue Heron Biotechnology have entered into a strategic development and distribution relationship. Invitrogen will invest in Blue Heron in exchange for worldwide rights to distribute custom gene synthesis services of Blue Heron Biotechnology based on its proprietary GeneMaker platform.

GeneMaker can synthesize any gene sequence with perfect accuracy regardless of complexity or length, which makes it ideal for the synthetic biology market. Researchers across the world are increasingly turning to synthetic genes as a cost-effective and convenient alternative for traditional cloning. The technology has allowed pharmaceutical and biotechnology companies to speed up the drug discovery process through an ability to rapidly and accurately synthesize known genes and produce from them novel proteins, new vaccines and diagnostics.

Invitrogen is a leading provider of recombinant cloning and protein expression products and the premier provider of the largest fully sequenced human open reading frame clone collections. Gene synthesis builds upon this strength and would be especially useful in emerging fields such as synthetic biology. The companies will co-develop new products and services for the research and bio-pharmaceutical markets, as part of the pact.


Sanofi-Aventis enters pact with ImmunoGen for TAP tech

ImmunoGen Inc., the United States, and Sanofi-Aventis, France, have signed an option agreement that enables the French the company to gain expanded access to Immunogens tumour-activated prodrug (TAP) technology.

ImmunoGen and Aventis Pharmaceuticals Inc., predecessor to Sanofi-Aventis had established a collaboration in 2003 to discover, develop and commercialize novel antibody-based anticancer products. As part of that, Sanofi-Aventis has exclusive rights to use ImmunoGens TAP technology with antibodies to targets included in the collaboration. Exercise of the option would now enable Sanofi-Aventis to use the technology also with antibodies to targets not included in the earlier collaboration. Sanofi-Aventis has also extended the duration of the research collaboration to the maximum length, that is until 2008.

ImmunoGen has developed potent cell killing agents specifically for antibody-directed delivery to cancer cells. The company has also developed alternative means (linkers) of attaching these agents, which are derivatives of the cytotoxic agent maytansine, to cancer cells and enabling the best design to be selected for each antibody and target.


Invitrogen to partner with Wave Biotech

Invitrogen Corporation and Wave Biotech, both in the United States, have entered into a partnership to supply media-filled disposable bioreactors. Under the agreement, Invitrogen Corporation will offer its GIBCO brand cell culture media products both standard and customized to the users of Wave Bioreactors in its branded O-series Cellbag disposable bioreactor bags.

Cell bags and disposable bioreactors are easily customized to suit specific cell culture process needs for research, development or cGMP manufacturing operations.


German industry collaborating on microbial genome research

Prominent companies in the pharmaceuticals, chemicals and nutrition industries in Germany have formed an industry and science association (Industrieverbund Mikrobielle Genomforschung) for advancing microbial genome research as a technology with broad industrial application, with the cooperation of the German Federal Ministry of Education and Research (BMBF) and various academic research groups.

The use of micro-organisms in industrial biotechnology is regarded as a key technology, making it possible to quantify and use the natural metabolic activity of micro-organisms more efficiently than the previously used methods. The new venture could advance sequencing methods and functional genome analysis, which could enable the genetic configuration of organisms to be revealed and compared within a very short time. This will enable the very complex ways in which micro-organisms interact with their environment to be made increasingly predictable and as a result, it will be possible to develop products and intermediates based on renewable materials.

Chemical Weekly, 2 January 2007


Male-specific algal gene points to evolutional sex differentiation

Researchers led by Dr. Hisayoshi Nozaki at the University of Tokyo, Japan, have shed light on one route by which evolution gave rise to reproduction through the joining of distinct sperm and egg cells. The findings indicated that a gene underlying the primitive system of reproduction was likely co-opted during evolution to participate in sex-specific sperm development.

The researchers established a genetic connection between the male sexuality of an oogamous multicellular green algal species Pleodorina starrii and one of the mating types of its isogamous ancestor, the unicellular alga Chlamydomonas reinhardtii. In C. reinhardtii isogamous sexual reproduction occurs through plus (MT+) and minus (MT-) mating types. MT- represents dominant sex because the MID (minus-dominance) gene of C. reinhardtii is both necessary and sufficient to cause the cells to differentiate as MT- isogametes. No sex-specific genes related to MID have been identified in closely related oogamous species. The researchers report that they have identified a version of the MID gene in P. starrii, the PlestMID. This gene was present only in the male genome and it encodes a protein localized abundantly in the nuclei of mature sperm. The findings indicated that P. starrii maleness evolved from the dominant sex (MT-) of its isogamous ancestor. The breakthrough in understanding provides an opportunity to address any number of very interesting questions regarding evolution of oogamy as well as the origins of male female dichotomy.


Adult hair follicles provide alternative stem cells

A team of scientists from the Medical College of Wisconsin, the United States, has identified the molecular signature of epidermal neural crest stem cells in mouse. The research resolved conflicting scientific opinions by showing that these cells were distinctly different from other types of skin-resident stem cells/progenitors.

Epidermal neural crest stem cells have a high degree of plasticity, can be isolated at high levels of purity, as well as expanded in culture. Similar to other types of adult stem cells, they are readily accessible through a minimally invasive procedure and can lead to using a patients own hair as a source for therapy without the controversy or medical issues of embryonic stem cells.
The researchers, led by Dr. Maya Sieber Blum, injected epidermal neural crest stem cells in mice with spinal cord injuries. When grafted into the spine, the cells survived and demonstrated several desirable characteristics that could lead to local nerve replacement and re-myelination. The subsets of the epidermal neural crest stem cells expressed markers for oligodendrocytes, the nerve supporting cells that are essential for appropriate neuron function.


Gene that colours red apple

Led by Dr. Mandy Walker, scientists at Australias Commonwealth Scientific and Industrial Research Organization have located a gene that controls the red colour of apples. The finding could help produce more brightly coloured apples, which are rich in anthocyanins that could boost human health through their antioxidant activity.

The researchers used the latest molecular technology to measure how much of particular genes expressed in apple skin as the fruit ripened and took colour. The team focused on master genes that were activated by light, as the apple requires light to turn red when it ripens. The team was able to show that the fruit colour can be predicted even in seedling apple plants by measuring the form of this gene. By identifying master genes that were activated by light, the researchers were able to pinpoint the gene that controls the formation of anthocyanins in apples. This gene is not expressed as much in green apples.


New map on human genetic variation unveiled

Dr. Charles Lee and colleagues at the Harvard Medical School in Boston, the United States, have unveiled a new human genetic map or book of life that fills in missing pages and chapters to explain how genes are involved in common diseases. The map looks at differences in duplications and deletions of large DNA segments known as copy number variants (CNVs) which could help explain why some people are susceptible to illnesses such as AIDS and others are not. Scientists identified 3,000 genes with variations in the number of copies of specific DNA segments. The changes can influence gene activity and disease susceptibility.

The Human Genome Project mapped the billions of letters that make up the human genetic code and later refined the map by looking for single variations in the arrangement of those letters, called single nucleotide polymorphisms (SNPs), which make individuals unique. The CNV map provides a different way to look for genes linked to diseases by identifying gains, losses and alterations in the genome.


Two genes offer clues on sterility and fatality in hybrids

Scientists at Cornell Universitys Department of Molecular Biology and Genetics, the United States, have made the first identification of a gene pair responsible for problems unique to hybrids. The researchers have found two genes from two fruit fly species (Drosophila melanogaster and D. simulans) that interfere with each other and thereby prevent the production of male offspring. This finding sheds light on what causes fatality in hybrids and offers clues to how species evolved from common ancestors.

The research focused on Hybrid male rescue (Hmr), a rarely occurring mutation in a D. melanogaster gene, and Lethal hybrid rescue (Lhr), a similar mutation in a D. simulans gene, that make these genes non-functional. The males survive when either of these genes are turned off and then crossed with the other fruit fly species. Researchers cloned each gene and inserted an Lhr gene from D. simulans into D. melanogaster and noticed the two genes did not interfere with each other in the engineered D. melanogaster strain, though the Lhr and Hmr genes interfere with each other in hybrids. The finding supports the Dobzhansky-Muller model that suggests hybrid incompatibilities are caused by genes that have evolved from a common ancestor but diverged in each of the species. The team found that when genes from each species were compared with each other, the Hmr gene in D. melanogaster and the Lhr gene in D. simulans evolved much faster than other genes and diverged because of natural selection, a genetic change caused by pressure that benefits the survival of a species.


Researchers identify gene linked to autism

Dr. Thomas Bourgeron and co-researchers at the Institut Pasteur, France, have discovered a new gene, named SHANK3, linked to autism, a mental disability that prevents sufferers from communicating and forming relationships. The gene has a key role in the organization of neuron connections.

The study sample included five people from three families with either autism or Aspergers syndrome and reported that the children studied had anomalies in the SHANK3 gene. Earlier the research team had identified anomalies on SHANK3, which produces the proteins necessary to construct synapses, the junctions between the brains neural pathways. Significant deletions to various degrees were found in the gene. The gene SHANK3 might help explain the communication difficulties, which provide major social obstacles to many sufferers.


Rust resistance genes located

Dr. Elaine Lagudah and colleagues at Australias Commonwealth Scientific and Industrial Research Organization have discovered a DNA marker for two key rust resistance genes namely Lr34 and Yr18, enabling plant breeders to cultivate more effective rust-resistant wheat varieties.

The study revealed that the genes Lr34 and Yr18 are inherited together and provide wheat plants with improved protection against leaf rust and stripe rust. Breeders can track the presence of this rust resistance through a simple DNA test in which the marker corresponding to the gene is present. The marker was proved effective in a range of wheats from different countries such as Australia, India, China and North America, and the International Maize and Wheat Improvement Centre (CIMMYT).



GM bacteria that eat cancer

Researchers from the Johns Hopkins Kimmel Cancer Centre, the United States, have decoded a genetically modified bacterium that has been found to eat tumours and secrete a protein. The discovery has opened up potential for packaged anticancer therapies. The modified bacterium, Clostridium novyi-NT, was found effective on cancerous growths that become starved of oxygen due to lack of organized blood capillaries feeding the growth. C. novyi-NT thrives in these oxygen-deficient areas, which are unique to cancerous growth, and kills the tumour from the inside out. Surrounding normal cells and the exterior of the tumour remain unaffected, as the bacterium dislikes oxygen-rich conditions.

When C. novyi-NT was tried on mice alongside liposome-packaged chemotherapy drugs, both large and small tumours were totally destroyed and two-thirds of the mice were permanently cured. These encapsulated drugs gravitate towards the tumours, as they are large to fit through the series of tightly woven blood vessels that surround normal tissue but are small enough to fit through the irregular blood vessel systems. Liposomase, the protein secreted by the bacterium, disrupts the lipid packaging of the drug and delivers the drug.


Mutation responsible for Noonan syndrome uncovered

Scientists at Harvard Medical School, the United States, have discovered that mutations in a gene called SOS1 account for many cases of Noonan syndrome, a common childhood genetic disorder characterized by short stature, facial abnormalities, learning disabilities, heart problems and predisposition to leukaemia.

To identify candidate genes, the researchers conducted genetic analysis in children with Noonan syndrome. These patients had neither PTPN11, which was stated by a previous study as a cause of Noonan syndrome, nor KRAS, the oncogene whose mutations were identified in a small subset of severe cases. From this group, the research team identified SOS1 mutations in about 20 per cent of the cases. After modelling the positions of the mutations on crystal structures of SOS1, the scientists made recombinant versions of the mutants and expressed them in mammalian cells. They discovered that the mutants promoted excessive activation of Ras/MAP kinase pathway, which is activated also by PTPN11 mutations. The results form the first example of activating mutations in an exchange factor in human disease, and will aid in the prenatal diagnosis and genetic counselling for the disorder.


Stem cell discovery brings regenerative heart therapy close

In the United States, researchers have discovered master cardiac stem cells with the capacity to produce all major heart tissues cardiac muscle, smooth muscle and endothelial types bringing heart tissue regeneration a step closer. The new findings were researched and published independently by teams led by Dr. Kenneth Chien at Massachusetts General Hospital and Dr. Stuart Orkin at Howard Hughes Medical Institute.

Dr. Chiens team traced the presence of an isl1 protein from islet-1 cardiac muscle progenitor in mice through to cardiac muscle, smooth muscle, endothelial, pacemaker and non-muscle cell types. They also showed that these cells could develop from embryonic stem cells. Dr. Orkins group isolated embryonic mouse cells that expressed the cardiac-specific gene Nkx2.5+ and found that these cells differentiated into both cardiac muscle cells and the conduction system cells that carry the electrical impulses that tell the heart to beat. Some of the cells expressed a second gene, c-kit, which has the ability to expand and produce both cardiac muscle and smooth muscle cells from a single cell.

The major problem associated with using embryonic stem cells in heart regeneration is the danger of uncontrolled growth leading to cancer. This is less likely to occur when using the more developed master stem cell cultures. The use of adult stem cells to treat heart patients is currently undergoing clinical trials in the United States on patients waiting for heart transplants.


Protein fingerprint in spinal fluid could spot Alzheimers disease

Researchers have long been seeking biomarkers in blood or cerebrospinal fluid that can identify the presence of Alzheimers pathology and distinguish it from other conditions that cause dementia. Scientists at Cornell University, Ithaca, the United States, have identified a group of 23 protein biomarkers in cerebrospinal fluid that can provide a neurochemical fingerprint to help identify patients living with Alzheimers disease.

The Cornell study combined cutting-edge proteomics technology, detailed image analysis, and complex computational and statistical analyses to simultaneously compare 2,000 cerebrospinal fluid proteins from 34 patients with autopsy-proven Alzheimers disease to those of 34 age-matched controls without the disease. This effort yielded 23 proteins that individually might not point to Alzheimers but together form an identifying pattern or fingerprint specific to the illness.

For example, some of the biomarkers are linked with proteins that clog the brain of Alzheimers patients. Other molecules are associated with inflammation, also a part of Alzheimers brain pathology. Still other proteins in the group are linked to synaptic dysfunction the breakdown of communication between brain cells that occurs as Alzheimers disease progresses. While the ultimate goal is a highly accurate test that patients and doctors could use to diagnose Alzheimers disease and guide its treatment, the finding has great relevance for current Alzheimers research.


Scientists discover early key to regeneration

A team of scientists led by Dr. Michael Levin at the Forsyth Institute, the United States, has discovered that programmed cell death is required for cell regeneration to occur. Through studies of the frog (Xenopus) tadpole, the team examined the cellular underpinnings of regeneration.

They chose Xenopus tadpole for studying regeneration, as it is an ideal model that is able to regrow a fully functioning tail and all components including muscle, vasculature, skin and spinal cord. The scientists studied the role of apoptosis played in regeneration in multi-cellular organisms. They investigated the dynamics of cell number control in the regenerating tail bud and showed that despite the massive tissue proliferation required to build the tail, an early apoptotic event was needed for regeneration to occur. Normal regeneration of the tail includes a small focus of apoptotic cells; when apoptosis is inhibited during the first 24 hours, regeneration cannot proceed and the growth of nerve axons becomes abnormal. Later inhibition of apoptosis has no effect, suggesting that the programmed death of a specific cellular component is a very early step in the regeneration programme.

This research might shed light on mechanisms necessary for therapeutic regeneration in humans of tissues that are lost, damaged or non-functional because of genetic syndromes, birth defects, accidents, cancer, degenerative diseases, aging and organ failure.


Gene discovered that causes familial pancreatic cancer

A team of international researchers led by Dr. Teri Brentnall of the University of Washington, the United States, has discovered that the mutated form of a gene called Palladin causes familial pancreatic cancer, a leading cause of cancer deaths. They also showed that the Palladin gene behaves abnormally in both hereditary and non-hereditary forms of pancreatic cancer, providing the possibility that by testing for a Palladin gene mutation it might be possible to detect the families that run the risk of inherited pancreatic cancer.

Palldin gene is involved with the cytoskeleton, the structural backbone of all human cells. When the gene is functioning properly, it gives a cell its shape and enables it to move. In the case of pancreatic cancer, a mutation in Palladin allows the cell to move much more quickly than normal cells and invade the surrounding healthy tissue. The researchers developed a surveillance programme for the early detection of pancreatic pre-cancer in families who inherit the disease. By using this on members of the Family X, a family afflicted with hereditary pancreatic cancer, the scientists identified those with initial stages of the cancer. They compared DNA samples from those with pre-cancer to those who did not have the disease and isolated the cancer-causing gene to an area of Chromosome 4. All members of Family X who had the Palladin mutation were found to be affected with pancreatic cancer or pre-cancer, while other members were cancer-free.


Genetic engineering helps cattle resist mad cow disease

Researchers led by Dr. Yoshimi Kuroiwa at Kirin Brewery Co., Japan, have reported the successful use of genetic engineering to produce cattle that resist the brain-destroying bovine spongiform encephalopathy (BSE), or the mad cow disease. They hope that the genetically engineered cattle could be the source that can provide dairy products, gelatin and other products free of BSE.
The study cattle were healthy at the age of 20 months and sperm from the males was used to make the normal embryos that were employed to impregnate cows. The cattle lacked the nervous system prions that cause BSE and other related diseases. Prion protein-negative cattle could be a preferred source of a wide variety of bovine-derived products that had been extensively used in biotechnology, such as milk, gelatin, collagen, serum and plasma. The researchers made the cattle known as knockouts because a specific gene had been knocked out of them using a method called gene targeting. They demonstrated, by knocking out the prion protein gene, that normal cellular prion protein was not necessary for the normal development and survival of cattle to produce healthy calves.



Scientists map structure of DNA-doctoring protein complex

Mobile DNA, which grafts foreign genes into chromosomes of target cells, is a powerful force that shapes evolution of species, but also spreads antibiotic resistance. It is used by bacteria that spread Lyme disease and by viruses linked to certain forms of cancer. Working with the lambda virus and Escherichia coli bacterium, biologists from Brown University, the United States, have deciphered the structure of a six-protein complex critical to this gene grafting act.

The scientits had earlier solved the structure of integrase, the protein surgeon that allows mobile DNA to cut into a chromosome, insert its own genes and then sew the chromosome back up. This work was conducted using the lambda virus that infects E. coli, which serves as a model that scientists use to understand mobile DNA.

The scientists have now identified the protein complex that acts as a team of nurses during this snip-and-solder procedure known as site-specific recombination. The structure is a three-dimensional representation of the DNA within this complex. It is pictured like a double helix decked with clumps of curly, colourful ribbon. The decoding of the structure enables the scientists to know how the six proteins interact with each other and fold DNA during site-specific recombination. Biologists now have a new tool to help them understand a variety of these complexes, including ones that control cell division, gene expression and the replication of DNA.


Protein-sugar combo could boost encapsulation stability

Dr. Anita Fechner and colleagues at the Friedrich-Schiller University Jena, Germany, report that a protein polysaccharide combination for stabilizing water-oil-water emulsions could lead to customized double emulsions with improved stability to changes in pH and temperature. These results are a basis for discovering new emulsifiers and can broaden the scope for using protein-stabilized emulsions in foods containing acid or salt.

Double emulsions involve water-based droplets dispersed inside oil droplets and further dispersed inside an aqueous phase. The study looked at the potential of stabilizing water-oil-water (W/O/W) emulsions with conjugates of sodium caseinate (SC) and dextran (Dex). Vitamin B12 was used as a model encapsulate and the release of the vitamin from the inner to the outer aqueous phase was measured.

The double emulsions with encapsulated B12 were prepared using a two-step process. The inner aqueous phase consisted of water, sodium chloride, gelatin and 1 per cent vitamin B12, and was homogenized to form the emulsion with the oil phase polyglycerol polyricinoleate and MCT-oil (caprylic/capric triglyceride, Miglyol 812), provided by Sasol Germany GmbH. The double emulsion was subsequently prepared by homogenizing the water-in-oil emulsion with a second aqueous phase containing the SC-Dex conjugate or pure SC. The conjugates were found to be smaller, with uniform size distribution. Using the SC-Dex conjugate emulsifier, when the pH of the emulsion was decreased to create an acidified environment, the release of vitamin B12 into the outer water phase reduced from 40 to 30 per cent. The research team is looking at ways to optimize the conjugate formation and other effects on double emulsions.


Stretch a DNA loop to turn off proteins

The physical manifestation of DNA loops is a consequence of many biochemical processes in the cell, such as the regulation of gene expression. These loops, therefore, indicate the presence of enzymes or other proteins that are turned on. Biologists led by Dr. Douglas Smith, the University of California, the United States, have discovered that stretching the DNA molecule could turn off the proteins known to cause these loops in DNA. This molecular model showed how some proteins form loops in DNA when they chemically attach or bind at separate sites to the double helical molecule that carries the genetic blueprint of life.

The researchers showed that certain enzymes acting on DNA can be turned off by mechanically manipulating and stretching single DNA molecules. This switching-off can provide a molecular mechanism for cells to be able to sense and respond to mechanical stresses that they might normally experience. Such stresses could be generated internally by the cells themselves, such as when a cell undergoes shape changes during the cell cycle, or as external stresses from the environment.

The amount of tension or stretching that needs to be applied to the molecule is very small only one pico-Newton or one-trillionth of the force generated by the weight of an apple.


Hydrolysed whey protein lowers blood pressure

At the University of Minnesota, the United States, Dr. Joel Pins and co-researchers have announced that a daily supplement of hydrolysed whey protein can lower blood pressure in hypertensive people. The researchers looked at the effects of a daily 20 g supplement of hydrolysed whey protein (experimental group) or an unmodified whey protein (control group) on 30 pre-hypertensive or stage 1 hypertensive people (defined as having a blood pressure between 120/80 and 155/95 mm Hg). Whey contains a variety of proteins with unique functional and nutritional characteristics such as beta lactoglobulin, alpha-lactalbumin, glycomacropeptide, serum albumin, lactoferrin, immunoglobulins and lactoperoxidase. These bioactive peptides are reported to be angiotension converting enzyme (ACE) inhibitory peptides.

Dr. Pins and team also observed an improvement of low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) levels. By inhibiting the ACE conversion of angiotensin I to the potent vasoconstrictor angiotensin II, blood flow and subsequently blood pressure were improved. The study gives link between protein consumption from vegetable sources and decreased risk of hypertension.


Engineered blood protein for electrolysis of water

Scientists led by Prof. T. Suchida, Waseda University, Japan, have combined two molecules that occur naturally in blood to engineer a molecular complex that uses solar energy to split water into hydrogen and oxygen, providing an alternative to electrolysis. The researchers synthesized a large molecular complex from albumin and porphyrin, a molecule that carries oxygen around the body and gives blood its deep red colour. Porphyrin molecules are usually found combined with metals and have an iron atom at their centre in the natural stage of blood.

The scientists modified the porphyrin molecule to swap the iron for a zinc atom in the middle, which completely changed the chemistry and characteristics of the molecule. This modified porphyrin molecule was combined with albumin and altered through genetic engineering to enhance the efficiency of the process. The resulting molecular complex proved to be sensitive to light and could capture light energy in a way that allows water molecules to be split into hydrogen and oxygen molecules. The breakthrough might help develop novel ways of creating hydrogen gas for use as fuel in the future.


The giant protein titin helps in muscles building

Scientists at the Hamburg Outstation of the European Molecular Biology Laboratory (EMBL) and collaborators from Kings College in London, the United Kingdom, have collaborated to discover that a protein called titin is crucial in the formation of muscle tissue. Under the microscope, muscle looks like millions of tiny pistons connected end to end into long rows called sarcomeres, which permit the contraction and relaxation of muscle that allow bodies to move. Sarcomeres are joined at the ends by Z-disks, thick bands of densely packed molecules. Titin, the largest protein made by human cells, is anchored in the Z-disk and is so long that it spans half the length of a sarcomere. Titins size and its position, which puts it into contact with all the components of sarcomeres, had pointed to a possible role for it in sacromere assembly.

The researchers obtained crystals of parts of the titin molecule bound to another protein, called telethonin, and analysed the crystals on high-energy X-ray beam lines. The extremely detailed images of the connections between the proteins revealed that telethonin has a kind of internal symmetry that lets it grasp two titin molecules running off in opposite directions, linking the tails in a unique way that might give some clues to sarcomere assembly. This work gives scientists a way to discover why some mutations in titin are linked to diseases.


Role of protein chaperone interactions in cystic fibrosis

Researchers at The Scripps Research Institute, the United States, have described key protein interactions that contribute to cystic fibrosis development. Cystic fibrosis is triggered by a genetic mutation that causes the defective folding and retention of a specific protein called cystic fibrosis transmembrane conductance regulator (CFTR) in the endoplasmic reticulum the part of the cell used for protein translation, folding and for preparation for transport to the surface of the cell. Normally, CFTR acts as a membrane channel for control of movement of sodium and chloride ions between the inside and outside of the cell. The correct salt balance across the cell surface is critical for water balance throughout the body.

The scientists used mass spectrometry and multi-dimensional protein identification technology to describe how the heat shock protein Hsp90 and other molecular chaperones and chaperone helpers control the stability of the CFTR protein. While more than 1,500 different mutations of the cystic fibrosis gene have been found by various studies, the dF508 mutation is the most common, occurring in approximately 70 per cent of all cystic fibrosis cases. In the present study, the scientists were able to reverse the disease process in cell culture for the dF508 mutation by partial siRNA silencing of the Hsp90 co-chaperone ATPases regulator Aha1. These findings might provide a new framework for the correction of cystic fibrosis and other protein folding diseases.



Enzyme breakthrough could help protect crops

Scientists from the Norwich Research Park, the United Kingdom, have claimed that an antibiotic-producing enzyme in oats can be used to protect major cereal crops from the fungal disease called take all, a disease estimated to affect half of the countrys wheat crops. The researchers, led by Prof. Anne Osbourn, found that the enzyme Sad2 helps produce a chemical that makes the plant resistant to infections. Sad2 functions in the roots and produces an antimicrobial at the site most vulnerable to fungal attack.

Researchers showed that the Sad2 gene had evolved from the ancient and highly conserved cytochrome P450 family by gene duplication and then diverged from its original role in sterols production to adopt the new function of producing an antimicrobial chemical called avenacin. The synthesis of avenacin is a multi-step process. The scientists have already identified five genes coding for different enzymes in this pathway and are isolating others. These genes were found clustered together in the genetic code of the plant; clusters of genes that have connected functions are often found in bacteria or fungi but are extremely rare in plants.


Tearing down of fungal cell wall

At the Virginia Bioinformatics Institute, the United States, Dr. Christopher Lawrence and colleagues have identified a fungal gene, namely AbNPS2, which plays an important role in the development and virulence of Alternaria brassicicola. A. brassicicola is a destructive pathogen that causes black spot disease on most cultivated Brassica crops worldwide, causing considerable leaf loss in important crops such as canola, cabbage and broccoli.

The investigators showed that disruption of the AbNPS2 gene drastically impacts the integrity of the cell wall of fungal spores produced in the reproductive phase of A. brassicicolas life cycle. The AbNPS2 gene most likely directs the synthesis of a molecule that plays an essential role in maintaining the structure of the cell wall of the conidia (spores). The spores of A. brassicicola are hydrophobic and water droplets placed on a lawn of fungal hyphae bearing normal spores are repelled and easily roll off the surface. When the AbNPS2 gene is disrupted, the linkage of the outermost layer of the fungal spore cell wall to the middle layer appears to be disturbed, destroying the architecture of the cell wall and making the spores permeable to water.

This has drastic effects on the viability of the spores.
The AbNPS2 gene encodes a large protein known as a non-ribosomal peptide synthetase, which directs the synthesis of secondary metabolites known as non-ribosomal peptides. The putative secondary metabolite produced by the protein encoded by this gene could serve as a physical bridge in the layers of the cell wall or function as a regulator of cell wall biosynthesis.


Human albumin from tobacco plants

Human serum albumin (HSA) is the intravenous protein most commonly used for therapeutic ends. HSA is employed to stabilize blood volume and to avoid risk of a heart attack. It is used for burns, haemorrhages, surgical operations or when there are symptoms of malnutrition, dehydration, chronic infections and renal or liver illnesses.

Agricultural engineer Alicia Fernndez San Milln, Spain, has developed a novel technique called plastidial transformation to produce HSA from tobacco plants in a recombinant form. According to her, plastidial transformation is an economically viable alternative, as it increases the levels of HSA by 10 to 100 times compared with levels obtained by nuclear transformation. Commercial albumin is currently extracted from blood, yeasts and mammalian cells.

With the nuclear transformation method, the gene is integrated into the DNA of the cell nucleus of the leaf and, thus, can manage only a small number of copies of the gene. With the plastidial system, on the other hand, the gene is introduced into the chloroplast, where photosynthesis takes place and where the genomes can multiply up to 10,000 times. The tobacco plant is very easy to handle genetically and is a great generator of biomass. Given that the protein is produced in the chloroplasts, the more the leaf biomass, the more albumin that can be got.


Gene breakthrough might lead to allergen-free groundnuts

At the University of Florida, the United States, Dr. Kang and his team have identified a new gene, called Ara h 3-im, in groundnuts (peanuts) that codes for a protein with no apparent allergic effects. Ara h 1, Ara h 2 and Ara h 3 are classified as important major allergens, which are recognized by more than 50 per cent of patients allergic to groundnut.

The scientists reported that a previously unidentified complementary DNA produced a protein with potentially reduced allergenicity. In the case of the newly identified Ara h 3-ims, the N-terminal sequence is different and distinct from the other allergens and this changes the proteins ability to bind to immunoglobulin E (IgE), an antibody that is capable of initiating powerful immune responses. Using a technique called immunoblotting, distinct differences were translated into the Ara h 3-im polypeptide not recognized by IgE, isolated from blood taken from groundnut-sensitive patients. This finding opens up the opportunity to genetically modify or breed mutationally a groundnut with the allergen Ara h 3 replaced by the non-allergen Ara h 3-im. Initial results indicate that Ara h 3-im has potentially lower allergenic properties than previously characterized groundnut allergens, which might aid in the production of a hypoallergenic groundnut.


Plant virus as delivery vehicle for green insecticide

Dr. Dov Borovsky and colleagues at the Florida University, the United States, have succeeded in modifying the plant-destroying tobacco mosaic virus (TMV) into one that fights crop pests and mosquitoes. The scientists genetically modified the TMV so that it produces an environmentally benign, natural insecticide called trypsin modulating oostatic factor (TMOF), thereby turning the pathogen into a microscopic chemical factory. The modified virus is harmless to plants.

The TMV produces TMOF in the protein coating its exterior surface and inoculated plants accumulate more TMOF when the virus reproduces. TMOF stops insects from producing a crucial digestive enzyme called trypsin and causes them to starve to death, unable to draw nutrients from food. The virus reproduces well in plants, but it cannot replicate itself from one generation of plant to another; farmers would therefore need to inoculate their crops each year.

By processing the leaves of the plants that have accumulated large amounts of TMOF, the chemical can be extracted and reduced to a powder to make effective mosquito control agents. The powder can be used in sprays to kill adult mosquitoes and mixed into baits that target mosquito larvae.


Sugar-gelatin alternative to pure gum Arabic

Dr. Vikas Kaushik and Dr. Yrj Roos from University College Cork, Ireland, have investigated gum Arabic, sucrose and gelatin in various ratios for the encapsulation of limonene, the major flavour in orange oil. A matrix of sucrose, gelatin and gum Arabic could encapsulate citrus flavours and offer a potentially cheaper alternative to pure gum Arabic in the encapsulation process.

Of the two previously reported concentrations of limonene encapsulated using the freeze-drying technique, the 9:1 (total solids:limonene, w/w) concentration resulted in the highest retention in the matrix. In the current study, with an encapsulation matrix consisting of equal measures of gum Arabic, sucrose and gelatin (1:1:1, w/w/w), 84 per cent of the limonene could be encapsulated. Electron microscopy revealed that the freeze-dried product was a dent-free, flake-like structure resistant to shrinkage. High retention levels of limonene in freeze-drying might be achieved by homogenizing the emulsion containing gum Arabic- sucrose-gelatin (1:1:1) at a single stage pressure of 100 MPa.


Super lettuce turns sour foods sweet

Researchers at the University of Tsukuba, Japan, have genetically engineered lettuce, a temperate annual or biennial plant most often grown as a leaf vegetable, into a living factory capable of producing large quantities of miraculin, a protein that could fool taste buds into thinking acidic foods and liquids are actually sweet.
Miraculin works by bonding to sweet receptors on the tongue. Sweet receptors stay on taste bud and accumulate sweet molecules, which set them off.

Normally they can be set off only by chemicals that are actually sweet, but miraculin distorts their shape and they become responsive to acids instead of sugar and other sweet things. The effect of miraculin lasts as long as the protein is bound to the tongue, which could be up to one hour. Miraculin makes most acidic foods taste sweet, though acids remain acidic, but does not improve the taste of bitter things.

The main natural source of miraculin is an African berry, Richadella dulcifica called miracle fruit, but it is difficult to extract miraculin from the berries and purify it. The scientists were able to obtain up to 40 micrograms of miraculin per gram of lettuce leaves, a tremendous amount considering the potency of the exotic protein.


Cotton: food for the millions?

Research spearheaded by the United States Agricultural Research Service (ARS) suggests that cottonseed could one day become a significant source of low-cost protein. The research team showed that by coupling RNA interference technology (RNAi) with a seed-specific gene promoter, it is possible to reduce gossypol levels within cottonseed and not reduce the levels of gossypol and related compounds in the foliage. The presence of gossypol in the foliage helps protect the plant from attack by insects. Gossypol is a toxic pigment that can be safely ingested only by ruminants with complex stomachs. Hence, most of the nutritious meal produced during cottonseed processing is currently sold as cattle feed.

Use of the RNAi technology to develop new cotton lines could lead to plants with low enough gossypol levels in the seed that the 44 million tonnes of cottonseed produced yearly could be used to provide roughly 10 million metric tons of protein: enough meet the total protein needs of almost a half billion people.



Tissue Mechanics

Tissue Mechanics describes the nature of the composite components of a tissue, the cellular processes that produce these constituents, the assembly of the constituents into a hierarchical structure, and the behaviour of the tissues composite structure in the adaptation to its mechanical environment. It is organized as a textbook for the student needing to acquire the competencies in the subject.

Contact: Ms. Eileen Purelis, Springer Science+ Business Media LLC, 233 Spring Street, New York, NY 10013-1578, United States of America. Tel: +1 (212) 460 1507; Fax: +1 (212) 460 1581


Nutrition and Genes: The Opportunities and Challenges of Nutrigenomics

As with all biotechnologies in the midst of rapid growth, nutrigenomics faces ethical, legal and social implications that will likely affect the public and the medical community. This book identifies and examines the anticipated risks and expected benefits of nutrigenomics from an ethical angle.

Handbook of Therapeutic Antibodies

Volume I of this comprehensive reference source for the development, production and therapeutic application of antibodies presents established technologies and clinical applications. Volume II provides a look at emerging technologies, new therapeutic concepts and clinical studies. The last volume features detailed and specific information about each currently approved type of antibody, including the clinical data.

Contact: John Wiley & Sons (Asia) Pte. Ltd., 2, Clementi Loop #02-01, Singapore 129809. Tel: +65 6463 2400; Fax: +65 6463 4604



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