VATIS Update Biotechnology . Mar-Apr 2011

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Biotechnology Mar-Apr 2011

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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Australia joins global fight against pandemic threats

In a collaborative effort among the United Nations Food and Agriculture Organization (FAO) and international and Indonesian scientists, a research team from Commonwealth Scientific and Industrial Research Organization (CSIRO), Australia, recently used a pioneering technique known as antigenic cartography to ‘map’ the evolution of the bird flu virus. While helping the Indonesian government protect its vast poultry flock against the deadly disease, this work also played a vital role in helping to manage the risk to Australia’s billion-dollar poultry industry. The outcomes from this technology are a major step forward in the fight against emerging infectious animal diseases (including bird flu) and the risks they pose to human health, global food security and animal health and welfare.

CSIRO scientist Dr. Peter Daniels said that the threat of global pandemic disease outbreaks is intensifying with the increases in the world populations of both people and farmed animals. “Two of the most disruptive and potentially catastrophic threats of the last decade have been from influenza viruses that originated in animal populations – the H5N1 bird flu and the pandemic H1N1 flu that evolved in pigs,” Dr. Daniels added. “To prepare for future outbreaks we need increasing cooperation, communication and sophistication in the way the animal health sector interacts with the public health sector.”

The World Organization for Animal Health (OIE) and FAO have joined forces to create a global network of expertise on animal influenzas, known as OFFLU. According to Dr. Daniels, Chairman of the OFFLU Executive Committee, the network offers a unique way of managing influenzas in the animal health sector while communicating directly with the public health sector. OFFLU will play an active role in the process that the World Health Organization (WHO) uses to select antigens for human influenza vaccines, similar to the ‘mapping’ work that CSIRO did to help the Indonesian government ensure poultry vaccines for bird flu are effective. As a member of the OFFLU network, CSIRO’s Australian Animal Health Laboratory is one of three laboratories in the world currently collaborating with WHO to generate the scientific data that guide this process, to protect against the threat of H5N1 flu becoming a pandemic.

Thailand and the Republic of Korea in research collaboration

The National Science and Technology Development Agency (NSTDA), a government research organization from Thailand recently signed a collaborative Memorandum of Understanding (MoU) with Korea Research Institute of Bioscience and Biotechnology (KRIBB), the Republic of Korea. The MOU provides KRIBB with an opportunity to explore research collaborative initiatives with any of the four research agencies of NSTDA. In the area of nanotechnology, talks between KRIBB and NSTDA’s National Nanotechnology Centre (NANOTEC) are focused on target drug delivery for anticancer applications.

“As Thailand is seeking to increase the amount of money spent on R&D to 1 per cent of GDP by 2013, NSTDA is working diligently to support this national policy and to become an S&T solution provider for major industries in Thailand,” said Dr. Thaweesak Koanantakool, President of NSTDA. “Working with capable partners such as KRIBB to exchange research knowledge and skill is a significant pathway towards accomplishing this goal,” said Dr. Yong Kyung Choe, President of KRIBB. “The research work at KRIBB on controlled antibody immobilization is very interesting to us,” said Dr. Warayuth Sajonsang, a NANOTEC researcher. “We feel our research focus on nanoparticles drug delivery compliment the work at KRIBB and can produce successful results that would be beneficial to healthcare sector.”

Philippines views biotech as a multi-billion industry in 2011

In the Philippines, the Congressional Commission on Science, Technology & Engineering (COMSTE) has prioritized the development of biotechnology for health and food security as one of its flagship projects for 2011, recognizing its vast potential for investment. Senator Mr. Edgardo J. Angara, Chair of COMSTE, has filed a senate bill, or the Biotechnology Industry Development Act of 2010, to support the initiative of the Commission. Mr. Angara pointed out that the world biotechnology industry is a multi-billion industry. Investment in medical biotechnology alone is estimated at US $200 billion, whereas investment in agricultural biotechnology was worth US$67 billion in 2003. The start of the 21st century indicates the coming convergence of agriculture and medicine with pharmaceuticals being produced by genetically engineered plants.

The proposed bill “intends to address the weaknesses of our system to enable the country to develop a biotechnology-based industry. The private sector is given incentives to invest in biotechnology research and development (R&D) by allowing the total R&D cost and prices of shares of stocks in biotech companies as tax deductible. Majority of the government’s investments in biotechnology R&D is awarded through a government corporation so as to lessen the burden of an unwieldy accounting and auditing system.” Mr. Angara said “It is more pressing now than ever to ensure that the country has the capability to create knowledge and harness innovation.”

Economic gains of Bt brinjal estimated at US$500 million

The National Centre for Agricultural Economics and Policy Research (NCAP) of the Indian Council of Agricultural Research (ICAR) has made an exhaustive socio-economic impact assessment of Bt brinjal (aubergine) in its Policy Brief “Economic Benefits of Bt Brinjal – An Ex-Ante Assessment.” The Policy Brief covers factors such as yield gain, reduction in insecticide use, benefits to farmers and consumers, as well as policy implications of adopting Bt brinjal hybrids. The brief estimates economic gains from the Bt brinjal hybrids annually to be US$126 million assuming adoption rate of 15 per cent, US$255 million at 30 per cent and US$500 million at 60 per cent in India – significant benefits in absolute terms for a vegetable with an aggregate area coverage much smaller than that of any major food crop.

The analysis revealed that the use of Bt brinjal hybrids could result in a significant reduction in insecticide use with the overall quantity of insecticides used against fruit shoot borer (FSB) reduced by 77.2 per cent. This amounted to 41.8 per cent reduction in the total insecticide use in brinjal. The reduction in insecticide use to control FSB would also generate large savings. The yield gain computed was 37.3 per cent over non-Bt brinjal hybrids and 54.9 per cent over popular brinjal hybrids. The study also showed that adoption of Bt brinjal hybrids would reduce the prices of brinjal by 3-15 per cent and thereby increase its consumption. A considerable increase in total production of brinjal from the existing area would amount to an additional production of 30,000-119,000 tonnes, which would improve the food and nutritional security of low-income consumers. In essence, Bt brinjal offers enormous welfare potentials such as benefits to farmers with higher income, reduced insecticide use and yield gain, and benefits to consumers with higher food and nutritional security and availability of brinjal free from FSB infestation.

France puts 260 million euros into research infrastructure

The French government has allocated 260 million euros in new funding over 10 years for nine national infrastructure projects in medical and life sciences research, as well as two demonstration projects in biotechnology. The funding is part of the first wave of a 35 billion euros economic stimulus package – now named ‘Investments for the future’ – announced by President Mr. Nicolas Sarkozy in December 2009. Of that amount, most of which has been borrowed from international financial markets, the government has allocated 21.9 billion euros to research and higher education. The 260 million euros worth of new grants brings the sums disbursed so far to 834 million euros. Further awards will be announced along with a second call for proposals.

Study reveals intricacies of biotechnology business

The opportunities that arise and whether or not they are exploited by biotechnology entrepreneurs depend to a large extent on how well connected is an individual business person and how well they mobilize their social network, says a new study. Ms. Cristina Sousa and colleagues at the National Institute of Engineering, Technology and Innovation, Portugal, explain combined studies from the technological entrepreneurship and social networking literature to uncover patterns in different network configurations.

The researchers looked at the origin, composition and structure of networks, and investigated how these variables affect the way key resources, both tangible and intangible, are used and how those affect and are affected by credibility and mediation. Previous researchers had shown that new enterprises in biotechnology were important to development of the industry. This is especially true in countries that are at an intermediate stage of development because they have a good science base and highly skilled people, but usually lack investment by large biotechnology companies. As such, scientific entrepreneurship can improve knowledge transfer and increase market value through human mobility, which is a critical factor in the growth of the biotechnology industry.

Ms. Sousa and colleagues affirm that the transformation of a technological opportunity into a commercial technology, product or service is a convoluted process, the success of which hinges on both the competence of people at the technological and non-technological level, as well as on the resources available. Success is determined not only by an entrepreneur’s capacity to identify an opportunity, but also by their ability to mobilize resources and skills. An entrepreneur’s established network and the ability to create useful new connections is usually the key. The team analysed 23 case studies from 61 biotechnology companies in Portugal for the study.


DuPont acquires Danisco

DuPont, the United States, has entered into a definitive agreement for the acquisition of Danisco, a global enzyme and speciality food ingredients company based in Denmark, for US$5.8 billion in cash and assumption of Danisco’s net debt of US$500 million. Upon closing, this transaction would establish DuPont as a leader in industrial biotechnology with science-intensive innovations that address global challenges in food production and reduced fossil fuel consumption. “Danisco has attractive, market-driven science businesses that offer clear synergies with DuPont Nutrition & Health and Applied BioSciences,” said Mr. Ellen Kullman, Chairman and CEO of DuPont.

The acquisition is expected to be financed with about US$3 billion in cash and the remainder in debt. The transaction is expected to close early in the second quarter and earnings are expected to increase in 2012, the first full year of the combined entity. “Danisco has two well-positioned global businesses that strongly complement our current biotechnology capabilities, R&D pipeline and speciality food ingredients, a combination that offers attractive long-term financial returns. This also would create new opportunities across other parts of the DuPont portfolio, including traditional materials science offerings,” added Mr. Kullman.

Eurofins signs agreement to acquire Lancaster Laboratories

Eurofins Scientific SE, Belgium, has signed a definitive agreement to acquire Lancaster Laboratories Inc. from Thermo Fisher Scientific Inc., the United States, for around US$200 million, subject to post-closing adjustments. Lancaster is a leading provider of pharmaceutical product testing services and current good manufacturing practice (cGMP) quality control in North America. In addition, it operates one of the leading environmental testing laboratories in the United States. Completion of the transaction is subject to regulatory approvals and customary closing conditions. Given that Lancaster is a single-site laboratory in the United States, no site consolidations or restructuring costs are foreseen as a result of this acquisition.

Ovarian cancer diagnostic patented in the United Kingdom

Australian diagnostics firm HealthLinx has been granted a United Kingdom patent for its protein biomarker ovarian cancer diagnostic OvPlex. The patent is the first granted to the company for its OvPlex test that uses a five-protein panel to aid early diagnoses of ovarian cancer in symptomatic women. HealthLinx is now looking to add another two proteins – AGR2 and HTX010 – to OvPlex’s panel in hopes of improving its performance. The initial results from the first stage of an ongoing 1,150-subject study suggest that adding the two new proteins could increase the test’s accuracy, the company says.

Amgen to acquire BioVex in a US$1 billion deal

In the United States, Amgen Inc. has agreed to acquire BioVex Group Inc., a biotechnology company that has two biologics in clinical development, including OncoVEX GM-CSF, a first-in-class oncolytic vaccine that may prove to be a paradigm-shifting approach to treating melanoma and other solid tumours. The transaction has been approved by the board of directors of each company. It is subject to customary closing conditions and is expected to close in the first quarter of 2011. Under terms of the agreement, Amgen will pay up to US$1 billion; US$425 million in cash at closing and up to US$575 million in additional payments upon the achievement of certain regulatory and sales milestones. Following the completion of the transaction, BioVex will become a wholly owned subsidiary of Amgen.

Optimer lands US$224 million licensing pact for its antibiotic

Japan’s Astellas is paying US$68 million upfront and promising up to US$156 million more in milestones on the future success of fidaxomicin, the experimental antibiotic from Optimer Pharmaceuticals Inc., the United States. The antibiotic had recently posted promising data. In return, Astellas gets exclusive rights to Europe as well as some other territories scattered around the globe. “We expect the Astellas collaboration will help Optimer realize the full potential of fidaxomicin and will help position this medication in these countries as the first line of treatment,” said Optimer’s CEO Mr. Pedro Lichtinger.

Fidaxomicin is an oral macrocyclic antibiotic for Clostridium difficile (CDI). In two late-stage trials fidaxomicin was equally effective in clinical cure when compared with vancomycin and was statistically superior to vancomycin. A 629-patient study reported that fidaxomicin reduced the rate of recurrence by 45 per cent when compared with vancomycin.

Agilent sets up R&D Lab in India

Agilent Technologies, based in the United States, has expanded its life sciences and chemical analysis centre of excellence in Bangalore, India. The company also has opened a life science application development lab, in an adjacent facility, to accelerate the discovery of life science analysis workflows. Together, the centre and lab cover 8,000 ft2, making this the largest Agilent research facility in the world. “India continues to be one of the most important markets for Agilent globally, with a significant presence of high-end R&D in pharmaceuticals and biotechnology,” stated Mr. Parmeet Ahuja, Country General Manager, Agilent Technologies, India. This will be the first Agilent lab facility where development of application solutions, customer interactions and training will take place in parallel. The combined facility plays an important role not just in applications and solutions development, but also in customer education.

Pfizer and Theraclone ink US$632 R&D deal for cancer and infectious diseases

In the United States, Theraclone Sciences has signed a deal with Pfizer Inc. in which Theraclone will use its I-STAR platform technology to help Pfizer identify monoclonal antibodies against up to four undisclosed targets – two for infectious disease and two for cancer. I-STAR can quickly test tens of thousands of antibodies to find those with the most biologic activity. Pfizer would get exclusive rights to therapeutic antibodies that are discovered in the course of the deal. Theraclone could earn up to US$632 million in research funding and milestone payments. Pfizer is responsible for preclinical and clinical development of the antibodies.

CEL-SCI begins Phase III clinical trial in head and neck cancer

CEL-SCI Corporation, the United States, has announced the commencement of Phase III clinical trial for Multikine®, its flagship immunotherapy. CEL-SCI has completed all of the manufacturing and regulatory requirements to begin enrolment of the study. The goal of this study is to establish Multikine as a first-line standard of care therapy in treating newly diagnosed head and neck cancer patients. The trial is believed to be the largest head and neck cancer study ever conducted and is called “IT-MATTERS,” an acronym for: Immunotherapy Multikine Anti-Tumour Treatments. The company expects to enrol about 880 patients at about 48 clinical centres in the United States, Canada, Hungary, Poland, Ukraine, Russia, India, Israel and Taiwan province of China in the clinical trial.

Novo Nordisk’s great hopes for next-generation insulin

Novo Nordisk, based in Denmark, has great hopes for degludec, its experimental next-generation insulin. This new insulin – which is slated for a regulatory filing later in the year – comes with an easier dispensing device and allows diabetics a flexible dosing schedule. Novo plans to highlight the data that demonstrates degludec significantly lowers the risk of night-time hypoglycaemia, when blood sugar levels plunge dangerously low as patients sleep. According to Novo’s Chief Science Officer Mr. Mads Krogsgaard Thomsen, the key to a successful rollout will be to get first-time insulin users to choose degludec. Once they become loyal to the insulin, they would not lightly consider switching. That could make degludec a big winner for Novo, as the number of new diabetics continues to grow at a rapid pace.


Anti-HIV gene therapy makes T-cells resistant to HIV infection

A team of researchers from Japan, the Republic of Korea and the United States has developed an anti-HIV gene therapy method in which a bacterial gene called mazF is transferred into CD4+ T-cells. The MazF protein is an enzyme (an mRNA interferase) that destroys gene transcripts, preventing protein synthesis. The design of this mazF gene therapy vector ensures that synthesis of the MazF protein is triggered by HIV infection. When HIV infects treated T lymphocytes, MazF is induced, blocking HIV replication and making the T-cells HIV resistant. “This study illustrates a unique way in which intracellular immunization can be achieved,” stated Dr. James M. Wilson, Director of the Gene Therapy Programme at the Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, the United States.

Triple amount of genetic information

Researchers from Van Andel Research Institute (VARI), the United States, have detected approximately 9,000 activated genes in samples from adult blood spots on Guthrie cards that had been archived anywhere from six months to three years. The team reports that their modified method uses commercially available tools and can be easily adopted by others in the scientific community for use on new-born blood spots. “Genetic information from Guthrie cards is a valuable resource,” said VARI Distinguished Scientific Investigator Dr. Jim Resau. “It opens doors to examine risk factors and potentially diagnose diseases before the clinical features are present. One such disease might be Cerebral Palsy, which currently cannot be diagnosed until a child is nearly two. The information could also be used to study paediatric cancers such as neuroblastoma, which is known to be present at birth in many cases,” he added.

Guthrie cards have been used for the past 20-30 years to collect blood for mandatory new-born screening programmes in Australia, Japan, New Zealand, the United States and most countries in Europe and South America. Blood is usually collected through a heel prick 24-48 hours after birth and is placed on the cards, which may be archived after screening. Although genetic material in blood from Guthrie cards has been presumed to be degraded because of varying storage conditions, VARI researchers were able to detect more than 3,000 activated genes in each sample in a 2009 study, and recently, they were able to detect three times that amount using the new method.

Function of molecule that underlies human deafness unveiled

In the United Kingdom, new research from the University of Sheffield has revealed that the molecular mechanism underlying deafness is caused by the mutation of a specific microRNA called miR-96. The discovery could provide the basis for treating progressive hearing loss and deafness. Researchers led by Dr. Walter Marcotti, Royal Society University Research Fellow from the University’s Department of Biomedical Science, in collaboration with Prof. Karen Steel at the Sanger Institute in Cambridge, discovered that the mutation in miR-96 prevents development of the auditory sensory hair cells. These cells are located in the inner ear and are essential for encoding sound as electrical signals that are then sent to the brain.

The new study has shown that miR-96 normally regulates hair cell development by influencing the expression of many different genes associated with a wide range of developmental processes at a specific stage. The mutation hinders the development of not only the mechanically sensitive hair bundle on the cell apex but also the synaptic structures at the base that govern transfer of electrical information to the sensory nerves. These new findings suggest that miR-96 is a master regulator responsible for coordinating the development of the sensory cells that are vital to hearing. Since the mutation in miR-96 is known to cause human deafness and microRNA molecules can drug targets, the work also raises new opportunities for developing treatments to treat hearing loss.

New species registered based on DNA-based description

In Sweden, the previously unknown species of ribbon worm discovered in Kosterhavet National Park in 2007 has now been scientifically named using a new method. Pseudomicrura afzelii, a form of nemertean or ribbon worm, has been described and registered by researchers at the University of Gothenburg using DNA technology. “We have shown that it is possible to move away from the traditional, highly labour-intensive way of describing a new species. Developments in molecular biology have made it possible to determine the genetic code for selected parts of DNA both quickly and cheaply,” says Dr. Malin Strand who, along with Dr. Per Sundberg, published the non-traditional description of the new nemertean. They have also deposited a type specimen of the species at the Gothenburg Museum of Natural History together with a test tube containing the species’ unique DNA. Thus, the species has been given its valid formal name and can be counted as a Swedish species. The two researchers have thus opened the door to new methods for determining species.

Draft ‘genetic road map’ of biofuels crop

The first rough draft of a “genetic road map” of a biomass crop is giving scientists in the United States an inside look at the genes of a crop that may help produce the next generation of biofuels. The study has produced the “transcriptome” of the species, prairie cordgrass, according to plant geneticist Mr. Jose Gonzalez of South Dakota State University. Mr. Gonzalez said the transcriptome can be used somewhat like a map – it records the genes the plant uses to reach certain goals.

One of the reasons scientists are interested in prairie cordgrass is because it yields extraordinarily well while tolerating wet conditions, high salinity and poorly aerated soils in low areas unsuitable for growing conventional crops. But it can also survive in open arid prairies. In the study, scientists used four tissues of prairie cordgrass to produce 556,198 expressed sequence tags, or portions of expressed genes. They assembled these into 26,302 “contigs,” or overlapping DNA segments from the same gene. “We calculated probably 40 per cent of the genes in prairie cordgrass, or more than 20,000,” Mr. Gonzalez said. The scientists are looking at the genes involved in particular traits such as cell wall composition, which is very important for biofuel production. Such studies can help the breeders eventually to select populations of prairie cordgrass with better composition.

The scientists are also interested in the morphological development of the plant because that is what supports the yield of the plant through many seasons – how the plant develops underground and starts growing at beginning of the season, how it goes into dormancy in fall, how it reactivates itself next season.

Genetically modified chickens do not transmit bird flu

Chickens genetically modified to prevent them from spreading bird flu have been produced in the United Kingdom by researchers at the Universities of Cambridge and Edinburgh. This genetic modification has the potential to stop bird flu outbreaks spreading within poultry flocks. This would not only protect the health of domestic poultry but could also reduce the risk of bird flu epidemics leading to new flu virus epidemics among humans.

To produce these chickens, the scientists introduced a new gene that manufactures a small “decoy” molecule that mimics an important control element of the bird flu virus. The replication machinery of the virus is tricked into recognizing the decoy molecule instead of the viral genome and this interferes with the replication cycle of the virus. When the transgenic chickens were infected with avian flu, they became sick but did not transmit the infection on to other non-transgenic chickens kept in the same pen with them. “We expect that the decoy to work against all strains of avian influenza and that the virus will find it difficult to evolve to escape the effects of the decoy,” said Dr. Laurence Tiley from the University of Cambridge’s Department of Veterinary Medicine. This is quite different from conventional flu vaccines, which need to be updated for virus evolution, as they tend to protect only against closely related strains of virus and not prevent spread within a flock.


Synthetic proteins that sustain life constructed

In a groundbreaking achievement that could help “building” new biological systems, scientists at Princeton University in the United States have constructed for the first time artificial proteins that enable the growth of living cells. The team of researchers created genetic sequences never before seen in nature and showed that they can produce substances that sustain life in cells almost as readily as proteins produced by nature’s own toolkit. “What we have here are molecular machines that function quite well within a living organism even though they were designed from scratch and expressed from artificial genes,” said Dr. Michael Hecht, a chemistry professor who led the research. “This tells us that the molecular parts kit for life need not be limited to parts – genes and proteins – that already exist in nature.”

Dr. Hecht’s research group set about to create artificial proteins encoded by genetic sequences not seen in nature. They produced about 1 million amino acid sequences that were designed to fold into stable three-dimensional structures. Once the team had created this new library of artificial proteins, they inserted those proteins into various mutant strains of bacteria in which certain natural genes previously had been deleted. The deleted natural genes are required for survival under a given set of conditions, including a limited food supply. Under these harsh conditions, the mutant strains of bacteria died – unless they acquired a life-sustaining novel protein from Dr. Hecht’s collection. This was significant because a bacterial colony formation under these selective conditions could occur only if a protein in the collection had the capacity to sustain the growth of living cells.

New method to analyse and quantify protein changes

In the United States, Dr. Kate Carroll, an associate professor in the Department of Chemistry at The Scripps Research Institute, has devised a new method of analysing and quantifying changes in proteins that result from a common chemical process. The findings could provide new insights into the effects of a highly destructive form of protein stress in various disease models, such as cancer. Dr. Carroll conducted the study with Mr. Young Ho Seo, a research fellow at the University of Michigan.

The new technique focuses on the process of cysteine S-hydroxylation that plays a significant role in a number of events related to physiology in both health and disease, including the regulation of signalling proteins in various disease states. The ability of the new technique to focus on signalling pathways is vital, as chronic disease states can involve the modification of signalling proteins through S-hydroxylation. Measuring the amount of S-hydroxylation at specific sites within a protein would help distinguish the proteins that may be involved in pathogenesis.

Dr. Carroll had earlier found that sulphenic acid served as an early warning biomarker of the reaction between hydrogen peroxide and cysteine. With the reaction target tagged with a fluorescent dye antibody, she could read the levels of sulphenic acid levels in cell lines, including breast cancer cells. The new technique allows scientists not only to quantify the modifications to various proteins but also to monitor these changes at the level of individual cysteines within a single protein. Dr. Carroll used a class of reagents called isotope-coded dimedone and iododimedone that traps and tags sulphenic acids, allowing the cysteine sites and modified proteins to be easily identified. The tagged proteins can be then be analysed by mass spectrometry.

Test to study proteins involved in neurodegenerative diseases

In Spain, scientists from the Institute of Biotechnology and Biomedicine and the Department of Biochemistry and Molecular Biology of the Autonomous University of Barcelona (UAB) have jointly developed and patented a method using yeast (Saccharomyces cerevisiae) to detect in human proteins the formation of oligomers – small toxic aggregations of molecules that can initiate the assembly of amyloid fibres found in neurodegenerative diseases. The test allows validating the efficacy of compounds that could dissolve or inhibit these aggregates, as well as studying at basic level the therapeutic potentiality of a large number of molecules. Oligomers are formed by the union of 2-20 molecules. Recent research seems to indicate that their toxicity is higher than that of amyloid fibres.

The new method locates and monitors in vivo the aggregation process of the protein using fluorescence techniques alone. It also allows studying compounds that inhibit oligomers as potentially therapeutic mechanisms to prevent posterior formations of amyloid plaques. The screening system was carried out by genetically modifying S. cerevisiae to link human protein aggregation to cell death. It is based on the fusion of the human peptide under study with the human variant of a protein needed for the survival of the modified yeast, dihydrofolate reductase (DHFR). The peptide aggregation deactivates DHFR protein and finally causes cell death, thereby providing a molecular detection system with tendency to aggregate and in which any compound capable of separating or inhibiting aggregation would favour cell survival.

Researchers carried out the study with the AB42 peptide, the main cause of Alzheimer’s disease. The system had efficacy only with compounds affecting oligomers, which makes it a very specific method for detecting the aggregation process. The system was also validated with chaperones, a group of proteins that increase the dissolution of protein aggregation and favour cell survival. The researchers validated the assay also by using proteins involved in Parkinson’s and Huntington’s diseases.

New method for rapidly producing protein-polymers

Bioengineers at Duke University, the United States, have developed a new method for rapidly producing an almost unlimited variety of human-made DNA sequences. These novel recombinant DNA sequences are used to produce repetitive proteins to create new types of drugs and bioengineered tissues. According to the researchers, current methods for producing these DNA sequences are slow or not robust and this has hindered the development of these increasingly important new classes of protein-based polymers. It has been already demonstrated that when a large protective macromolecule – a polymer – is attached to a protein, it greatly improves effectiveness and allows the protein to remain active in the bloodstream longer. There are many protein-polymer- based medications in use today, such as human growth hormones, drugs to stimulate blood cell formation in cancer patients and anti-viral agents.

“The new technique should be very useful in making a practically unlimited number of these protein building blocks,” said Dr. Ashutosh Chilkoti, Theo Pilkington Professor of Biomedical Engineering at Duke’s Pratt School of Engineering. The scientists used the system to synthesize genes found in two protein-polymer classes. In one, they produced protein-polymer combinations for elastin, a ubiquitous heat-controllable protein found in connective tissue. In the other, they rapidly synthesized novel glucagon-like peptide-1 (GLP-1) analogues to show variable pharmokinetic properties. GLP-1 is a hormone that acts to release insulin in the body.

Powerful methodology for stabilizing proteins developed

In the United States, a team of scientists at The Scripps Research Institute have found a new way to stabilize proteins. When the team attached a specific oligomeric array of sugars called a “glycan” to proteins having a defined structure, the proteins were up to 200 times more stable in the test tube. In the body, this stability may translate into longer half-lives for therapies, possibly lowering the overall cost of treatment for certain protein-based drugs and requiring patients to have fewer injections during a course of treatment.

The new research shows simple engineering rules do exist for achieving stability of glycoproteins in the test tube. It showed that proteins could be dramatically stabilized by integrating the standard N-glycan into a particular part of the protein – a structure known as a “reverse turn” containing a certain combination of amino acids. Reverse turns are found in the vast majority of proteins, making this methodology broadly applicable. The scientists tested their ability to increase the stability of proteins by creating glycoproteins from proteins that are not normally glycosylated – leading to increased stabilization in the test tube. These scientists have not yet looked at how long the proteins survive in the bloodstream – that work is currently under way. But the team is confident that the principles they discovered will now give scientists a new way to predictably stabilize proteins by design.

Mystery about recognition of unfolded proteins solved

For proteins to carry out any biological function, they must first assume specific three-dimensional (3D) shapes. However, a number of reactions have been described in recent years, where an interaction partner does not assume its active structure until the actual binding process commences. The great mystery as to how the binding partners could actually recognize such unstructured proteins is now being unveiled in Germany by scientists led by Prof. Thomas Kiefhaber from Technical University of München.

The scientists posed the question of whether local properties are sufficient for the recognition or the unstructured binding partner first had to assume a specific spatial structure. Possible candidates were regularly structural elements such as coiled a-helices or b-pleated sheets, in which internal hydrogen bonds are formed. The model system was the enzyme ribonuclease S, which in its active form comprises the S-protein and an a-helical S-peptide. While the S-protein has a defined 3D shape, the S-peptide on its own is initially unfolded. The researchers attempted to determine whether the S-protein recognizes the unstructured S-peptide or a small fraction of peptide molecules in their helical conformation.

Time-based measurements of the binding process of the altered peptide have now shown that the hydrogen bonds in the S-peptide, and as such in the a-helical structure, do not form until after bonding to the S-protein. Thus, they cannot play a role in the recognition process. Protein-protein recognition in this case takes place via hydrophobic interaction of the S-protein with the two spatially clearly defined areas of the unstructured S-peptide. These results are of importance for understanding the mechanism of protein-protein interactions. In the future, this method can be used to examine in detail the structure formation in proteins in other systems as well.


Pre-clinical studies with therapeutic cancer peptides reported

Q Chip Ltd., the United Kingdom, has successfully completed pre-clinical studies with formulations of two leading therapeutic cancer peptides. The peptides – Q-Leuprolide for prostate cancer and Q-Octreotide for acromegaly – were formulated using Q Chip’s innovative drug delivery platform, Q-SpheraTM. The platform enables development of long-acting injectable therapeutics with tailored release profiles and improved administration. It offers the potential for pharmaceutical companies to extend product life cycles and find the best ways to deliver novel complex biotherapeutics. The pre-clinical results demonstrated sustained release of Q-Leuprolide over both one and three months, and Q-Octreotide over one month.

Study results have shown that Q Chip platforms permit high levels of drug loading at high encapsulation efficiency in monodisperse microspheres, with controllable burst release after injection and near-zero-order release kinetics across the test period. Excellent correlations between in vitro and in vivo release profiles were observed. According to Q Chip’s Executive Chairman Mr. Ken Powell, “We have successfully engineered out of the microsphere manufacturing process the use of harsh solvents, high temperature and shearing forces.”

Blood vessels for laboratory-grown tissues

Researchers from Rice University and Baylor College of Medicine (BCM), the United States, have broken one of the major roadblocks on the path to growing transplantable tissue in the lab: they found a way to grow the blood vessels and capillaries needed to keep tissues alive. “The inability to grow blood vessel networks – or vasculature – in lab-grown tissues is the leading problem in regenerative medicine today,” said lead co-author Dr. Jennifer West, Bioengineering Department Chair and the Isabel C. Cameron Professor at Rice.

As its base material, a team of researchers led by Dr. West and BCM molecular physiologist Dr. Mary Dickinson chose polyethylene glycol (PEG), a non-toxic plastic widely used in medical devices and food. The scientists modified PEG to mimic the body’s extracellular matrix – the network of proteins and polysaccharides that make up a substantial portion of most tissues. They combined the modified PEG with two kinds of cells – both of which are needed for blood vessel formation. Using light that locks the PEG polymer strands into a solid gel, they created soft hydrogels that contained living cells and growth factors. After that, they filmed the hydrogels for 72 hours. By tagging each type of cell with a different coloured fluorescent marker, the team was able to watch as the cells gradually formed capillaries throughout the soft, plastic gel. To test these new vascular networks, the team implanted the hydrogels into the corneas of mice, where no natural vasculature exists. After injecting a dye into the mice’s bloodstream, the researchers confirmed normal blood flow in the newly grown capillaries.

Stem cell study could aid motor neuron disease research

Scientists have found a new way to generate human motor nerve cells in a development that will help research into motor neurone disease. In the United Kingdom, a team from the Universities of Edinburgh, Cambridge and Cardiff has created a range of motor neurons from human embryonic stem cells in the laboratory. It is the first time that researchers have been able to generate a variety of human motor neurons that differ in their make-up and display properties depending on where they are located in the spinal cord.

The research could help scientists better understand motor neurone disease. The process will enable scientists to create different types of motor neurons and study why some are more vulnerable to disease than others. In motor neurone disease – a progressive and ultimately fatal disorder – these cells break down leading to paralysis and difficulty in speaking, breathing and swallowing. In the latest study, scientists have found a way to generate a wider range of motor neurons using a process without retinoic acid. Prof. Siddharthan Chandran, Director of the Euan MacDonald Centre for Motor Neurone Disease Research at the University of Edinburgh, said “Motor neurons differ in their make-up, so understanding why some are more vulnerable than others to disease is important for developing treatment for this devastating condition.”

Bacterial enzyme boosts fight against brain tumours

New research in the United States has shown that oncolytic viruses engineered to destroy cancer cells might be more effective in treating deadly brain tumours if equipped with an enzyme that helps them penetrate the tumour. The enzyme, called chondroitinase, helps the cancer-killing virus clear its way through the thickets of protein molecules that fill space between cells and impede the virus’ movement through the tumour, say researchers at the Ohio State University Comprehensive Cancer Centre-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute who conducted the study. When tested in animals transplanted with a human glioblastoma, the most common and deadly form of brain cancer, the enzyme-armed virus improved survival by 52 per cent compared with controls, and in some cases eliminated the tumour entirely.

The enzyme is derived from Proteus vulgaris, an intestinal bacterium. It removes sugar chains that branch from molecules called proteoglycans that fill the narrow spaces between cells. By cutting away these branches, the enzyme clears a path that helps the virus spread through the tumour. Studies have shown that the enzyme-laden virus penetrates tumours in the animals’ brain significantly better than the enzyme-free control virus. “Overall, our results indicate that an oncolytic virus armed with this enzyme can have a significantly greater anticancer effect compared with a similar virus without the enzyme,” stated study leader Dr. Balveen Kaur, Associate Professor of Neurological Surgery.

Probiotic treatment for ulcers

Researchers from Spain have identified a strain of probiotic bacteria that may be useful in treating ulcers caused by Helicobacter pylori, considered one of the major risk factors for developing gastritis and gastric and duodenal ulcers. Antibiotic-based treatment for H. pylori infection is neither sufficient nor satisfactory, state the researchers, with the most successful treatments reaching 75 to 90 per cent eradication rates. Therefore the use of probiotics is a potentially promising tool to prevent H. pylori, they add.

Among probiotics Bifidobacterium is one of the favourite genera in studies focused on the prevention of gastrointestinal infection and is often used in fermented dairy products or food supplements. In the new study, the researchers tested numerous strains of bifidobacteria isolated from the faeces of breast-fed infants for activity against H. pylori. They identified a strain, Bifidobacterium bifidum CECT 7366, that had an inhibition level of nearly 95 per cent in vitro under certain conditions and tested its activity against infection in mice. After 21 days, the mice treated with the potentially probiotic strain developed significantly less ulcers than the control group. Additional tests suggest that treatment partially relieved damage to gastric tissue caused by H. pylori infection. Ingestion of the bacteria did not induce any disease or mortality in both immunocompromised and healthy mice. “The results confer to strain B. bifidum CECT 7366 the status of a probiotic bacterium with functional activity against H. pylori,” state the scientists.

Stem cell transplants help repair kidney damage

Transplanting of autologous renal progenitor cells (RPCs) – kidney stem cells derived from self-donors – has been found to improve kidney structure and function in rat models with kidney damage from pyelonephritis, a type of urinary infection that has reached the kidney. “Advancements in stem cell therapies and tissue engineering hold great promise for regenerative nephrology,” stated Dr. Abdol-Mohammad Kajbafzadeh, corresponding author of the study, from Tehran University of Medical Sciences, Islamic Republic of Iran.

The scientists divided 27 rats into three groups, two of which were modelled with an induced pyelonephritis in their right kidneys, while the third group did not have induced disease. RPCs were obtained from the diseased animals’ left kidneys and injected into the right kidney six weeks later. Two weeks after injection, tubular atrophy was reduced. After four weeks, fibrosis was reduced and after 60 days, right renal tissue integrity was ‘significantly improved’. “We propose that kidney augmentation was mainly due to functional tissue regeneration following cellular transplantation,” said Dr. Kajbafzadeh. “Kidney-specific stem/progenitor cells might be the most appropriate candidates for transplantation because of their inherent organ-specific differentiation and their capacity to modulate tissue remodelling in chronic nephropathies.” The researchers concluded that because renal fibrosis is a common and ultimate pathway that leads to end-stage renal disease, amelioration of fibrosis may be of major clinical relevance.

NIH scientists unveil characteristics of HIV early in transmission

A new finding from scientists at the National Institutes of Health in the United States could help efforts to design vaccines and other prevention tools to block human immunodeficiency virus (HIV) in the early stages of sexual transmission, before infection takes hold. Researchers from the NIH National Institute of Allergy and Infectious Diseases have helped explain genetic differences that can distinguish some early-transmitting HIVs – viruses found in an infected individual within the first month after infection – from forms of HIV isolated later in infection. These genetic features help HIV bind tightly to a molecule called integrin a4b7. This likely enhances the ability of certain HIV viruses to complete the many steps of sexual transmission and become the “founder” virus that establishes infection in an individual.

The study also sheds light on CD4+ T cells, the primary immune cell targeted by HIV. Scientists had earlier reported that gp120, an HIV surface protein, can bind to integrin a4b7 via a receptor on the surface of the CD4+ T-cell. a4b7 helps direct HIV-infected CD4+ T cells into the gut, where the virus begins to replicate fast. Given the new finding, the scientists believe it is likely that CD4+ T cells with the a4b7 receptor play an important role in the sexual transmission of HIV.


Green Super Rice

Green Super Rice is a mix of more than 250 different potential rice varieties and hybrids variously adapted to difficult growing conditions such as drought and low inputs, including no pesticide and less fertilizer, and with rapid establishment rates to out-compete weeds, thus reducing the need for herbicides. More types of Green Super Rice that combine many of these traits are in the pipeline. Green Super Rice is already in the hands of national agricultural agencies in major rice-growing countries for testing and development. The new rice variety is an example of what is needed as part of a “Greener Revolution” called for by rice scientists around the world and is one of the driving concepts behind the Global Rice Science Partnership (GRiSP) – a plan to improve international partnerships in rice research, its delivery and impact that would also ensure that rice is grown in an environmentally sustainable way.

Technique allows identification of key maize genes

Scientists in the United States have identified the genes related to leaf angle in corn (maize) – a key trait for planting crops closer together that has led to an eight-fold increase in yield since the early 1900s. The study, by researchers from the Agricultural Research Service (ARS) of the United States Department of Agriculture (USDA), North Carolina State University and Cornell University, is the first to relate genetic variation across the entire maize genome to traits in a genomewide association study. The researchers have so far located 1.6 million sites on the maize genome where one individual may vary from another, and they used those sites to identify the genes related to changes in leaf angle. Yield increases have mostly resulted from adaptations that breeders made to maize for planting it closer together for crop density. Along with changes in roots and nutrient uptake, which also play roles in higher crop densities, the leaves of maize crop plants have become more upright to maintain access to sunlight in crowded plots.

The team of researchers found that natural mutations in genes that affect ligules – the first thick part of the leaf where it wraps around the stalk – contributed to more upright leaves. Also, the changes in leaf angle result from many small genetic effects added together; while leaf angles may vary from one maize variety to another by up to 80°, the biggest effect from a single gene was only 1.5°. “Although each gene and variant has a small effect, we can make very accurate predictions,” said Dr. Ed Buckler, senior author of the study, an ARS research geneticist in Cornell’s Institute for Genomic Diversity and a Cornell adjunct Associate Professor of plant breeding and genetics. The genomewide association study allows the researchers to examine a corn plant’s genome and predict a trait with 80 per cent accuracy. This would be analogous to predicting the height of a person by sequencing and analysing their genes, or genotyping a seed to predict traits of the plant. The methodology may be applied to other traits, crops and species, including animals.

Plants cloned as seeds

Plants have been cloned as seeds for the first time in a research undertaken by plant scientists at University of California, Davis, (UC Davis), the United States, and their international collaborators. The research is a major step towards making hybrid crop plants that can retain favourable traits from generation to generation. When hybrids go through sexual reproduction, their traits, such as fruit size or frost resistance, get scrambled and may be lost, explained Dr. Simon Chan, Assistant Professor of plant biology at UC Davis and an author of the paper. “We are trying to make a hybrid that breeds true,” he added, so that plants grown from the seed would be genetically identical to one parent. “The new discovery gets to the same result as apomixis, although by a different route,” Dr. Chan said.

DThe researchers focused their work on the laboratory plant Arabidopsis, which has certain genetic mutations that allow it to produce diploid eggs without sexual recombination. These eggs have the same genes and number of chromosomes as their parents, but cannot be grown into adult plants without fertilization by sperm. In the new study, Mr. Chan’s lab, with colleagues from India and France, crossed Arabidopsis plants programmed to eliminate a parent’s genes with either of two mutants that can produce diploid eggs. In about one-third of the seeds produced, the diploid eggs were successfully fertilized, and then the chromosomes from one parent were eliminated, leaving a diploid seed that was a clone of one of its parents.

Agave has potential as the new bioenergy feedstock

The suitability of Agave as a bioenergy feedstock can sustain high productivity in spite of poor soil and stressful climatic conditions accompanying climate change. Agave grows successfully under hot, dry conditions and is currently used in the production of beverages and food and fibre. It is now being considered a promising source of biofuel. According to Mr. E. Garcia-Moya, a professor of botany at Colegio de Postgraduados en Ciencias Agricolas in Texcoco, Mexico, “Agave is a potential candidate as a bioenergy feedstock because it does not compete for land with the production of commodities.” Waste remaining in the fields after harvest, and created during production of tequila and mescal, has the potential to provide thousands of tonnes of bioenergy feedstock per year for bioenergy production, the researchers say.

Genetic study on disease resistance in maize

In the United States, crop scientists and plant pathologists from the Agricultural Research service (ARS) of Department of Agriculture (USDA) and five universities are sifting through millions of genetic sequence variations in the genes of maize (corn) to identify 51 gene regions associated with resistance to Southern corn leaf blight disease, a major plant pathogen. Dr. Jim Holland, a crop science professor at North Carolina State University (NC State) and an ARS research geneticist, and co-authors Dr. Peter Balint-Kurti, an ARS research plant pathologist and geneticist working in NC State’s Plant Pathology Department, and Mr. Kristen Kump, an NC State graduate student, joined researchers from Cornell University, the University of Delaware and the University of Missouri to examine a set of 5,000 maize varieties called the maize nested association mapping population. Using this population allowed the researchers to zero in on the parts of the genome that confer the resistance. The scientists said the search for Southern corn leaf blight resistance gene regions in maize is like looking for a specific house in a large city without knowing the address.

“Using this nested association mapping population, when we find associations with Southern corn leaf blight disease, we know we are on the right street and may be have the right house,” Dr. Holland stated. “If we know which genes control disease resistance, we can make better predictions about which maize varieties will be resistant to disease and focus on breeding those lines.” Dr. Holland and Dr. Balint-Kurti hope to build upon these results to learn more about how genes confer resistance to Southern corn leaf blight and whether they may also provide resistance to other similar types of diseases in corn and other plant species.

Potential bioenergy feedstock could fight weeds

Researchers at the Centre of Advanced BioEnergy Research of University of Illinois in the United States report that several herbicides used on corn also have good selectivity to Miscanthus x giganteus (Giant Miscanthus), a potential bioenergy feedstock. “No herbicides are currently labelled for use in Giant Miscanthus grown for biomass,” said Mr. Eric Anderson, an instructor of bioenergy. “Our research shows that several herbicides used on corn are also safe on this rhizomatous grass.” M. x giganteus is sterile and predominantly grown by vegetative propagation, or planting rhizomes instead of seed. This can be a very costly investment and needs a 1-2 year establishment period. Mr. Anderson’s research showed that the grass does not compete well with weeds during establishment, especially early emerging weeds.

The study screened 16 post-herbicides and 6 pre-herbicides in a greenhouse setting. Several herbicides, particularly those with significant activity on grass species, caused plant injury ranging from 6-71 per cent and/or reduced M. x giganteus dry mass by 33-78 per cent. Researchers then narrowed these herbicides down to the safest options and evaluated them in field trials replicated over two years. Field trials confirmed the greenhouse experiments. Pre-emergence herbicides and herbicides with broadleaf-specific activity generally did not produce significant injury or reduce above-ground biomass, while herbicides with considerable grass activity tended to cause injury in the range of 22-25 per cent and reduce biomass by 69-78 per cent.

While there remains no approved label use for herbicides on M. x giganteus for biofuel production, Mr. Anderson hopes this research can serve as a foundation either for growers to begin an IR-4 speciality product process or for a major chemical company to add it to their label in the future.

Genetic origin of cultivated citrus determined

A team of researchers from Southwest University, China, has conducted a study that provides genetic evidence of the origins of a variety species of today's cultivated citrus. The team, led by Dr. Zhiqin Zhou, analysed amplified fragment length polymorphism (AFLP) fingerprints – a technique that has been used successfully to assess the origin of potato cultivars – with chloroplast DNA (cpDNA) sequence analysis and nuclear internal transcribed spacer. “The combination of nuclear DNA and cpDNA data allowed us to identify the exact genetic origin of the cultivated citrus,” the researchers wrote.

The results proved that lemon were derived from citron and sour orange, and grapefruit was a hybrid that originated from a cross between sweet orange and pummelo. The data demonstrated that sweet orange and sour orange were hybrids of mandarin and pummelo, while rough lemon was a cross between citron and mandarin. The data also confirmed that bergamot was a hybrid of sour orange and citron, with sour orange as the maternal parent and citron as the paternal parent. The evidence confirmed a species of Papeda to be the female parent and Citrus medica as the male for Mexican lime. The researchers said that a clear understanding of the citrus genetic background is necessary for better characterization and utilization of citrus germplasm, and that this research will provide important new information for breeding of citrus.


DNA Nanotechnology: Methods and Protocols (Methods in Molecular Biology)

Currently, nanotechnology is exposing the properties of DNA in unprecedented detail leading to new insights on the biological behaviour and function of DNA. This book shows the procedures to follow to repeat methods that lead to such constructs or to the mastering of the characterization techniques used to study them. Topics covered in this guidebook include methods for preparing the nanostructures; advanced instrumental techniques to manipulate and characterize molecules and nanostructures; lists of the necessary materials and reagents; step-by-step, readily reproducible laboratory protocols; and notes on troubleshooting and avoiding known pitfalls.

Contact: Humana Press, 999 Riverview Drive, Suite 208, Totowa, NJ 07512, United States of America. Tel: +1 (973) 2561 699; Fax: +1 (973) 2568 341; Website:

Stem Cells and Neovascularization in Tissue Engineering

Tissue engineering is considered a promising new tool to improve the repair and restoration of tissue function and to rebuild new tissues. Stem cells are being extensively studied for use in tissue engineering because of their ability to develop into a variety of tissues. This volume addresses various scientific and engineering principles and technologies associated with the regenerative capabilities of stem cells. It provides results of preclinical and clinical trials and provides guidelines for the use of stem cells in tissue engineering and regenerative medicine.

Contact: CRC Press, 6000 Broken Sound Parkway, NW (Suite 300), Boca Raton, FL 33487, United States of America. Tel: +1 (800) 2727 737; Fax: +1 (800) 3743 401; E-mail:


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