VATIS Update Biotechnology . Nov-Dec 2008

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Biotechnology Nov-Dec 2008

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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US$100 million awarded for innovation in health research

Investigating anti-dengue proteins and testing dietary supplements for children with diarrhoea are among 105 projects that have received grants to explore uncharted areas in health research. The funding – US$100,000 for each project – was announced in October, as part of the Bill and Melinda Gates Foundation’s “Grand Challenges Explorations” initiative, which aims to encourage innovative ideas in health research.

An expansion of the Grand Challenges in Global Health programme, the initiative is a five-year, US$100 million funding scheme targeting early stage research to help scientists quickly establish the viability of their ideas. Mr. Pattamaporn Kittayapong, an associate professor at Thailand’s Mahidol University, won a grant to look for anti-dengue proteins that might be produced when mosquitoes are co-infected with the dengue virus and its bacteria Wolbachia. Such proteins could potentially be used as an antiviral dengue therapy.

This round’s awardees come from 22 countries in five continents, with just under 10 per cent awarded to researchers in developing countries. “The Grand Challenges Explorations grants were developed to lower the barriers to funding for anyone with a transformative idea for global health,” says Mr. Andrew Serazin, programme officer at the Gates Foundation’s Global Health Discovery. A key objective is to involve scientists who don’t typically work in global health, such as those from the developing world.


India’s agri-biotech set to touch US$5 billion by 2010

The biotechnology industry is advancing at a fast pace in India and is expected to become a US$5 billion industry by 2010, said Dr. P.G. Chengappa, Vice Chancellor, University of Agricultural Sciences, Bangalore. The agriculture sector, in particular, is likely to benefit the most from advances in biotechnology, he added, delivering the keynote address at a recent national conference on the “Impact of Biotechnology in India”. He identified investment thrust areas as vaccines, diagnostics, bioactive therapeutic proteins, bio-pesticides, bio-fertilizers, seeds, amino acids, and speciality bio-chemicals and plastics.

Outlining the developments in transgenic crops, Dr. Chengappa stated: “Bt cotton is already a success story. Other transgenic crops like rice, cabbage, tomato and brinjal are in field trials. This market is estimated to touch US$400 million by 2008. There is scope for development of varieties resistant to pest, disease and drought.” The total consumption of biotech products in India is estimated to be US$2,186 million, which is likely to touch US$4,270 million.

Source: www.safetybio.agri.

China to help Pakistan’s agriculture sector research

China will help Pakistan to broaden the long-term scientific collaboration in research and technical areas in agriculture sector, and a Memorandum of Understanding has already been inked in this regard. According to Dr. Ghulam Jilani, a member on crop sciences at the Pakistan Agricultural Research Council (PARC), PARC and the Chinese Academy of Agricultural Sciences (CAAS) would co-operate in water resource management, as well as in hybrid cotton, maize and other transgenic crops. Dr. Jilani said CAAS and PARC have reaffirmed their mutual interest focusing on the broad areas of science and technology. The two agencies will work for mutual benefits in animal science, plant science, soil science, agriculture, natural resources management and other related fields.


Brazil says yes to stem cell research, again

A few months back, Brazil’s Supreme Federal Court voted by a narrow margin to uphold legislation allowing research on embryonic stem (ES) cells, after almost three years of deadlock. The country permits research using ES cells under its Biosafety Legislation, approved in March 2005, although several limitations are applied, such as only using embryos created by in vitro fertilization and frozen for three years.

The decision in 2005 was contested by Brazil’s then Attorney General, Mr. Claudio Fonteles, who said that the legislation was against the right to life and human dignity, and therefore unconstitutional. The Ministers of the Court began discussing Mr. Fonteles’ petition in March this year. After intense debates, the Court decided by six to 11 votes in favour of upholding the 2005 approval without amendments. The remaining five Ministers also voted to uphold the basic legislation, but with restrictions.


Australia supports health and medical research initiatives

Australia has announced A$132 million (US$85 million) in National Health and Medical Research Council (NHMRC) Programme Grants and Fellowships, as well as the NHMRC European Union Collaborative Health Research Grants. Eight new programme grants, totalling A$73 million (US$47 million), will allow outstanding researchers to lead large teams at universities or institutes to focus on broad research areas, such as mental health, diabetes or cardiovascular disease. The funding allows research teams five years to pursue the best research options in their field.

The 2009 programme grants cover, among others, stopping the progress of mental illness, pathways to diabetes prevention and neural connections in the adult brain. Fifteen health care professionals across the country have also been awarded five-year practitioner fellowships. Another 80 of the best and brightest researchers will be able to pursue their careers in their areas of interest through 2009 NHMRC research fellowships. Five grants totalling A$2.40 million (US$1.55 million) will support health research projects co-funded by the European Commission, and carried out within Australian and European research institutions. Study areas include genetic factors in osteoporosis, twin studies in genetics, motorcycle safety, preventing weight gain and cancer gene-environments.



South Africa approves growing GM sorghum

South Africa has taken another step forward in the field of crop biotechnology. After a rancorous debate over whether genetically engineered sorghum, called “Super Sorghum”, should be grown in greenhouses, the South African government has given its nod to the project. The decision is a setback to anti-GMOs activists in South Africa who had waged a relentless campaign against the new sorghum variety.

Super Sorghum is nutritionally enhanced with more amino acids. The government’s decision has been lauded as “testimony that South Africa had robust biosafety laws” by the Council for Scientific Industrial Research (CSIR), which led the move to get approval. “We respect the fact that decision-makers have an obligation towards safety and that rigorous investigations are part of the process. Work on the project will now continue in our Level 3 biosafety greenhouse,” said CSIR Biosciences Executive Director, Dr. Gatsha Mazithulela. The project is being spearheaded by Dr. Florence Wambugu, a well known agricultural biotechnologist from Kenya.


RCUK opens Indian office

The Research Councils of the United Kingdom (RCUK) opened an office in New Delhi, India, in October with the objective of removing barriers to research collaboration between the two countries. Mr. John Beddington, the United Kingdom’s Chief Scientific Advisor, said that with its tradition of research excellence and ambitious plans for the future, India was an immediate choice for inclusion in the first group of RCUK overseas offices. RCUK had opened its first two overseas offices in November 2007, in Beijing, China and Washington DC, the United States.

The Indian office will focus primarily on four areas: technology for development, health research, energy and environmental change, and space technology, said Mr. Allan Thorpe, Chief Executive for the Natural Environment Research Council, one of the seven research councils that form RCUK. The office will attempt to link India’s and United Kingdom’s research programmes in the same areas, and look for further funding opportunities. It will also work with Indian funding bodies to share strategies, increase dialogue on funding priorities, and pursue and promote collaborative research opportunities.



Collaboration on Alzheimer’s disease candidate vaccines

GlaxoSmithKline Biologicals S.A. (GSKBio), Belgium, and AFFiRiS GmbH, Austria, have inked a collaboration agreement granting GSKBio exclusive rights to develop and commercialize two Alzheimer’s disease vaccine candidates that are based on AFFiRiS AFFiTOPE technology and currently in Phase I clinical development. AFFiRiS is also granting GSKBio exclusive option to develop and commercialize alternative Alzheimer’s disease vaccine candidates that are in pre-clinical development.

Under the terms of the agreement, AFFiRiS will receive an up-front payment of €22.5 million and could be eligible for future milestone payments as well as royalties. The total potential value of the agreement could reach €430 million in the event of full commercial success of the candidate vaccines. The agreement is subject to governmental authority approval.


Bayer CropScience aims to expand rice seed sale in Asia

Bayer CropScience AG, Germany, plans to expand substantially the breeding and marketing of commercial rice seed in the Asian region, with the aim of increasing the production volume eight-fold by 2017. “Furthermore, we want to intensify our research and development activities in Asia and bring a number of new rice varieties with improved plant traits to market,” explained Prof. Friedrich Berschauer, Chairman of the Board of Management of Bayer CropScience AG, at the inauguration of the company’s new rice development centre in Thailand.

The global demand for rice is expected to grow by around 30 per cent in the next 15 to 20 years, while the production is not being able to keep up. “One way of closing this gap is with hybrid rice,” Prof. Berschauer said. “We are convinced that the development and commercialization of seed with a higher yield potential is a major option for making rice production sustainably more efficient.”

Bayer CropScience has extensive expertise in the field of classical breeding and development of hybrid rice. The company markets conventional hybrid rice varieties under the Arize® brand in seven countries, which together represent over half of the world’s rice cultivation area. They include major rice producers such as Brazil, India, and Indonesia. High-quality Arize seed combines excellent genetic purity and germination capacity with a yield potential that is at least 20 per cent above that of classic rice varieties, the company claims.


Eli Lilly to fork out US$6.5 billion for ImClone

In the United States, the global pharmaceutical company Eli Lilly and the cancer therapeutics company ImClone have entered a US$6.5 billion merger agreement, under which Eli Lilly will pay US$70 per share of ImClone. Eli Lilly’s offer also represents a 51 per cent premium over ImClone’s closing price as on 31 July. Eli Lilly expects the transaction to close in the fourth quarter of 2008 or the first quarter of 2009. The company says that it is not subject to financing; the deal should be accretive to earnings on a cash basis in 2012 and on a GAAP basis in 2013.

With this deal, Eli Lilly will be able to add Erbitux to its portfolio of drugs. In 2007, worldwide sales of Erbitux grew 18 per cent to approximately US$ 1.3 billion. ImClone’s pipeline has a number of drugs in mid- to late-stage development that will add to Eli Lilly’s 13 clinical candidates. Eli Lilly has cited this as the reason for its acquisition. ImClone also has a significant focus on biologics, which Eli Lilly is trying to boost. In addition, Eli Lilly will gain from ImClone’s development and commercial centre.


Biotech firms target enhanced GM maize markets

Global biotechnology companies Monsanto and Dow AgroSciences (DAS) are now eyeing markets for more potent and pest-resistant GM maize (corn) after the successful marketing of Bacillus thuringiensis (Bt) corn since 2003. Bt corn has been promoted for its built-in resistance to Asiatic corn borer.

Before even setting foot in other Asian countries, biotechnology companies have already seen opportunities in starting out in the Philippines. The country is internationally recognized for having a more established regulatory policy on biotechnology. DAS already started its field testing of the TC 1507 variety in 2005 in the country. “We have already completed two seasons of field testing. Hopefully it will be approved for release next year,” said Mr. Antipas Criador IV, Head of regulatory and field R&D at DAS. Aside from being corn borer-resistant, TC 1507 also prevents infestation from lepidopterans such as catworms and earworms. DAS, however, did not claim resistance to other pests, saying that they are yet to resolve the data interpretation issue with the Bureau of Plant Industry.

Meanwhile, Monsanto has started testing of a multiple-gene GM corn this year. Unlike the first-generation Bt corn, which has only one gene, the second-generation Bt corn, called the Mon89, has three genes, a Monsanto official said. Monsanto will be completing its first season field trial this November. (Source:



QIAGEN acquires Biosystems unit of Biotage

QIAGEN N.V., the Germany-based provider of sample and assay technologies, has acquired all assets related to the Biosystems business from Biotage AB, the Sweden-based developer, manufacturer and distributor of products for genetic analysis and medicinal chemistry. The transaction is valued at approximately US$53 million in cash (subject to certain customary purchase price adjustments) and performance milestone payments of up to approximately US$7 million over the next four years.

Biotage’s Biosystems unit is best known for its Pyrosequencing®, which has become a fundamental technology in next-generation sequencing. It has developed PyroMark instrumentation, the world’s first real-time sequence detection system, to automate the use of the Pyrosequencing technology. The system has key advantages over other sequence analysis technologies in short length sequence detection and quantification. It is a synergistic addition to other detection technologies from QIAGEN.



Pharmicell to bring stem cell therapy to European market

Pharmicell Europe GmbH, Germany, has received the official authorization for production of somatic cell therapeutics derived from adipose tissue. The licence allows to produce and market adipose tissue-derived stem cells in Europe. With this permit, Pharmicell can provide its cell product Twelve Cell SolutionTM for a wide range of plastic-aesthetic therapies, such as wrinkle and skin treatments, breast augmentation, and breast reconstruction after breast cancer surgery and radiation. Pharmicell is the first in Europe to provide GMP-certified fat cell products for clinical uses. Its Twelve Cell Solution is produced from patient’s own fat tissue-derived cells, a composition consisting of stem cells, fat cells and other regenerating cell types. The fat tissue is processed under GMP conditions to isolate the cells, which will then be reapplied to the patient.



Rockeby biomed gets R&D grants from SPRING Singapore

Rockeby biomed, a Singapore-based healthcare group, has been awarded two grants by SPRING Singapore under the Technology Enterprise Commercialization Scheme (TECS). The first grant of S$250,000 (US$165,000) awarded under Proof of Concept (POC) is for the development of a magnetic detection platform for influenza A, including avian flu, while the second grant of S$ 500,000 (US$330,000) is awarded under Proof of Value (POV), to scale-up the production of a rapid and sensitive test incorporating fluorescence technology for the field diagnosis of influenza A.

The POC project is planned to take one year, after which, the platform will give Rockeby a unique patent protected technology that can also be applied to human seasonal influenza. Under POV, the project is planned to take two years. The platform can then be expanded to other infectious disease tests such as Chlamydia, Dengue and Foot & Mouth. Both projects have been approved for funding by TECS, and work to develop faster and more sensitive tests for influenza A, which has been the subject of pandemic fears worldwide.



Scientists find genes that increase lung cancer risk

An international research team has identified two genetic variations that appear to increase a person’s risk of developing lung cancer by up to 60 per cent. The same research team had earlier identified another gene that raised lung cancer risk. “We are looking at differences in the DNA that makes you more or less likely to develop lung cancer,” said Dr. Paul Brennan, a cancer epidemiologist at the World Health Organisation’s International Agency for Research on Cancer.

The study included scientists from 18 countries who analysed genetic mutations in more than 15,000 people – 6,000 with lung cancer and 9,000 without the disease. The researchers discovered a region on the fifth chromosome containing two genes – TERT and CRR9 – where they believe variations can boost the likelihood of lung cancer by as much as 60 per cent.

Not much is known about CRR9, but pinpointing the TERT gene is promising because it activates an enzyme called telomerase, which is key to aging and cancer, Dr. Brennan said. Implicating the TERT gene in a specific cancer can help lead to a better understanding of how cancer develops and boost the design of new drugs to stop tumours, he added.


Novel mechanism for regulation of gene expression

The Conaway Lab of Stowers Institute for Medical Research, the United States, has demonstrated that an enzyme called Uch37 is kept in check when it is part of a human chromatin remodelling complex, INO80. Uch37 is a “deubiquitinating enzyme” that can remove ubiquitin (protein tags) from other proteins. The presence of one kind of ubiquitin on a protein can mark it for destruction, while others serve as marks to affect the activity of a protein. INO80 is believed to function in both gene regulation and DNA repair by “unpacking” DNA from nucleosomes to allow access to chromosomal DNA.

Previously, the Conaway Lab had demonstrated Uch37’s association with another multi-protein complex, the proteasome – a large protein complex that degrades proteins that are unneeded or damaged. The new study shows that when bound to INO80, Uch37 can also be activated in the presence of proteasomes. “Our findings suggest that activation of INO80-associated Uch37 by transient association of proteasomes with the INO80 complex could be one way proteasomes help to regulate gene expression,” said Dr. Tingting Yao, a Post-doctoral Research Fellow and lead author on the paper.

“Tingting’s discovery of communication between INO80 and the proteasome provides new clues into the functions of both of these regulatory complexes,” said Dr. Joan Conaway, senior author on the paper. “In addition, it provides new insights into how deubiquitinating enzymes can be regulated. The ability to regulate these enzymes is very important because promiscuous removal of ubiquitin marks could lead to a failure to regulate properly the activities or levels of key enzymes and proteins in cells.” The ultimate goal of the Conaway Lab is to understand how genes are turned on and off during transcription and how regulation of chromatin structure contributes to this process.


Scientists sequence genome of cancer patient

Scientists in the United States have, for the first time, decoded the complete DNA of a cancer patient and traced her disease – acute myelogenous leukaemia (AML) – to its genetic roots. A large research team at the Genome Sequencing Centre and the Siteman Cancer Centre at Washington University School of Medicine sequenced the genome of the patient and the genome of her leukaemia cells, to identify genetic changes unique to her cancer.

The pioneering work sets the stage for using a more comprehensive, genome-wide approach to unravel the genetic basis of cancer. “Our work demonstrates the power of sequencing entire genomes to discover novel cancer-related mutations,” says Dr. Richard K. Wilson, Director of Washington University’s Genome Sequencing Centre and senior author. “A genome-wide understanding of cancer – which is now possible with faster, less expensive DNA sequencing technology – is the foundation for developing more effective ways to diagnose and treat cancer.”

Based on genetic testing with traditional methods, the patient was known to have two mutations that are common among AML patients, an indicator that she had a typical subtype of the disease, and one of the reasons why her genome was selected for sequencing. The researchers discovered just 10 genetic mutations in the tumour’s DNA that appeared to be relevant to the patient’s disease: eight of the mutations were rare and occurred in genes that had never been linked to AML. Of the eight novel mutations discovered, three were found in genes that normally act to suppress tumour’s growth. One of these mutations is in the PTPRT tyrosine phosphatase gene, which is frequently altered in colon cancer.

The scientists also showed that virtually every cell in the tumour’s sample had nine of the mutations, and that the single genetic alteration that occurred less frequently was likely the last to be acquired. They suspect that all the mutations were important to the patient’s cancer. Four other mutated genes appear to be involved in molecular pathways that promote cancer growth. In particular, one mutation was found in a gene family that also is expressed in embryonic stem cells and may be involved with cell self-renewal. Interestingly, the researchers note, self-renewal is thought to be an essential feature of leukaemia cells.


Genetic code of Spirulina platensis cracked

Thailand’s centre of expertise for biotechnology, National Centre for Genetic Engineering and Biotechnology (BIOTEC), reports that its scientists have successfully cracked the genetic code of blue-green algae, Spirulina platensis, and aim to complete sequencing the organism’s genome by early next year. The project was conducted in partnership with King Mongkut University of Technology Thonburi, Kasetsart University and Chiang Mai University.

The 24-member project team working on the decoding of the S. platensis genome was led by Associate Professor Supaporn Cheevadhanarak of King Mongkut University of Technology Thonburi and Assistant Professor Jeerayuth Chaijaruwanich of Chiangmai University. Dr. Somvong Tragoonrung, a BIOTEC researcher in the team, said that they chose to decode the genetic sequence of S. platensis because of its complexity, which had caused problems for teams in other countries. “We have completed sequencing 90 per cent of the S. platensis genome, which has around 5.8 million base pairs,” he added. Thailand is ranked third in the world for production of S. platensis.


First glimpse of a key DNA repair protein at work

Repairing breaks in the two strands of the DNA double helix is critical for avoiding cancer. In humans and other organisms, a molecular machine called the MRN complex is responsible for finding and signalling double-strand breaks (DSBs), and then launching the error-free method of DNA repair called homologous recombination. Dr. John Tainer of the Life Sciences Division at the United States Department of Energy’s Lawrence Berkeley National Laboratory, leading a team of his colleagues from the Scripps Research Institute, has revealed how the central component of the MRN complex performs its essential functions.

DSBs occur naturally about ten times a day in every human cell; they are one of the most highly toxic and mutagenic kinds of DNA damage, implicated in cancer as well as many other diseases. Because cancer cells are more susceptible to damage than many normal cells when dividing, DSBs are created deliberately in most cancer therapies to kill dividing tumour cells. The deliberate inactivation of DNA repair pathways may be an even more powerful method of killing cancer cells, because cancer cells often have defects in repair or signalling of DNA damage that would cripple them if left unrepaired.

The MRN complex is hence a key target for both new cancer therapeutics and for controlled gene targeting to treat inherited disorders. The core of the MRN complex is the protein Mre11. However, without good models of how Mre11 interacts with DNA, it was impossible to know how Mre11 recognizes the ends of the broken DNA and how it remodels DNA sequences. Dr. Tainer’s team resolved this by going beyond images of the stand-alone structure of Mre11 to study Mre11 bound to DNA during the first steps of DSB repair.

What the team found is that Mre11 not only finds the ends of broken DNA strands and links them together but also remodels the DNA in preparation for the work of other repair proteins, an essential function of Mre11 on which successful homologous recombination depends. Further studies allowed the researchers to determine how mutations of the mre11 gene affect the protein’s ability to do its job and in some cases to cause disease.


Landmark study unlocks stem cell’s DNA secrets

In a pathbreaking study led by an eminent molecular biologist at Florida State University (FSU), the United States, researchers have discovered that as embryonic stem (ES) cells turn into different cell types, there are dramatic corresponding changes to the order in which DNA is replicated and reorganized. The findings bridge a critical knowledge gap for stem cell biologists, enabling them to better understand the enormously complex process by which DNA is repackaged during differentiation – when ES cells, jacks of all cellular trades, shed this pluripotency to become masters of specialized functions.

Using mouse and human ES cells, FSU scientists led by Dr. David M. Gilbert have shown, with unprecedented resolution along long stretches of chromosomes, which sequences are replicated first and which occur later in the process of differentiation. “Understanding how replication works during embryonic stem cell differentiation gives us a molecular handle on how information is packaged in different types of cells in manners characteristic to each cell type,” said Dr. Gilbert. “That handle will help us reverse the process in order to engineer different types of cells for use in disease therapies.”

Dr. Gilbert identified two major therapeutic hurdles thus: “First, the methods currently used rely on the unnatural retroviral insertion of genes into patients’ cells, and these genes are capable of forming tumours. Second, this method is very inefficient as well because only one in 1,000 cells into which the genes are inserted becomes pluripotent.” He said there is a need to learn how cells lose pluripotency so that the process can be efficiently reversed without risks to patients.

The problem, however, is that adult cells are very specialized and have tucked away the information they no longer need on how to become other cell types. But, Dr. Gilbert noted, one time that the cell “shows its cards” is during DNA replication. “During this process, which was the focus of our FSU research, it is not just the DNA that replicates,” he said. “All the packaging must be replicated as well in each cell division cycle.” He explained that ES cells have many more, smaller domains of organization than differentiated cells, and it is during differentiation that they consolidate information. ‘Domain consolidation’ is the name that the scientists have given to the new concept they discovered.



Breakthrough in genetic map of wheat

Scientists from the French National Institute for Agricultural Research (INRA) said they have constructed a map of the largest wheat chromosome – chromosome 3B. The research demonstrates that it may be possible down the road to map out the entire wheat genome, which is five times larger than the human genome and 40 times larger than that of rice. More than 15 countries are taking part in the International Wheat Genome Sequencing Consortium (IWGSC) that attempts to sequence the whole genome of wheat, which is one of the world’s leading cereal crops and a staple food for one-third of the world’s population. INRA is helping to lead IWGSC, which includes countries such as Australia, the Czech Republic, Israel and the United States.

The genetic map of wheat is considered as particularly instructive to scientists, because unlike many “diploid” plants and animals, which have just two sets of chromosomes, wheat is a “polyploid” – the term used to describe organisms with three or more sets of chromosomes. The research study can be used to better understand genetic questions pertaining to a range of widely cultivated polyploid plants, including wheat, cotton and tobacco.



Unusually flexible ‘two-in-one’ enzyme

Scientists from Ruhr-University Bochum, Germany, have solved the structure of an unusually flexible enzyme in a virus that infects marine cyanobacteria Prochlorococcus. The virus can produce specific pigments more effectively than its host can. It requires only one enzyme, in contrast to the host Prochlorococcus, which needs two enzymes. The virus makes use of phycoerythrobilin synthase, a “two-in-one” enzyme.

Mr. Thorben Dammeyer, a member of the research team led by Prof. Nicole Frankenberg-Dinkel, solved the 3D structure of the enzyme. He discovered a flexibility that allows sections of the protein to assume different positions – an unusual property for proteins in combination with their substrate. In contrast to its cyanobacterial relatives, the P-SSM2 virus does not harvest light for photosynthesis using red and blue pigments; it employs chlorophyll, just like higher plants. “We have discovered the genetic blueprint for an enzyme within the virus. This enzyme is capable of producing the red pigment more effectively than its host, which has convinced us that the pigment cannot be unimportant for Prochlorococcus, even if it is not required for light trapping,” Prof. Frankenberg-Dinkel stated.

The scientists used X-ray diffraction analysis to determine the 3D structure of the enzyme at atomic resolution both alone and in complex with its natural substrate, the green biliverdin IXa. This molecule was found in the binding pocket of the protein, where the conversion into a red pigment takes place. Prof. Frankenberg-Dinkel explained that the scientists were able to see how different parts of the enzyme around the binding pocket are capable of assuming different positions.


A molecular identity crisis: a ribozyme without RNA!

Not all enzymes that are assumed to require an RNA component in order to function do actually contain RNA. This surprising discovery was made during a project that focused on RNase P enzyme. Contrary to the accepted scientific theory, a research team from Vienna, Austria, has proved that certain forms of RNase P do not contain any RNA.

Ribozymes are enzymes that function only in the presence of RNA, and hail from a long-gone age when biochemical processes were still controlled by RNA molecules. RNase P, an enzyme that modifies transfer RNAs, is one such ribozyme. All previously characterized forms of this enzyme confirmed assumptions about their RNA component. Yet, evidence has also been uncovered over the past two decades that has cast doubt on the universality of this finding and indicated that this enzyme could be made up solely of proteins.

The research team, led by Prof. Walter Rossmanith at the Medical University of Vienna, has provided conclusive evidence by successfully identifying the components of human mitochondrial RNase P. “RNase P is made up of three proteins that are solely responsible for the catalytic capacity of the enzyme without any RNA,” says Prof. Rossmanith. The identification of the three proteins also resolved another question in molecular evolution research: how is a ribozyme replaced by a protein enzyme? The answer is that the protein-only mitochondrial RNase P developed in parallel to a pre-existing ribozyme. Eventually, it replaced the latter. It is interesting to note that the three protein components have been recruited from entirely different biochemical pathways and yet they have nevertheless retained their original functions.


A motor protein that rewinds DNA

Two biologists at the University of California-San Diego (UCSD), the United States, have discovered the first of a new class of cellular motor proteins that “rewind” sections of the double-stranded DNA molecule that become unwound in “bubbles” that prevents the expression of critical genes. In humans, this would ultimately lead to death, said Dr. Jim Kadonaga, a professor of biology at UCSD who headed the study. “What we discovered is the enzyme that fixes this problem,” he added.

The UCSD researchers’ findings are also important because they provide biomedical scientists with a greater understanding of the molecular mechanisms that lead to a rare genetic disorder called Schimke immuno-osseous dysplasia. “We knew this particular protein caused this disease before we started the study,” said Dr. Kadonaga. “We just didn’t know what it did.” What HepA-related protein (HARP) did astounded Dr. Kadonaga and Dr. Timur Yusufzai.

The two molecular biologists had earlier found that HARP burns energy in the same way as enzymes called helicases and, like helicases, are attached to the dividing sections of DNA. But while helicases use their energy to separate two annealed nucleic acid strands, this protein did the opposite – it rewinds sections of defective DNA and thus seals the two strands together again. The UCSD biologists termed their new enzyme activity an “annealing helicase”. Dr. Kadonaga says, “Just as there are DNA-DNA helicases, there are RNA-DNA helicases and RNA-RNA helicases. So it doesn’t take a lot of imagination to foresee that there are probably going to be RNA-DNA annealing helicases and RNA-RNA annealing helicases. The field potentially can be fairly large.”


Protein ‘tubules’ hide avian flu virus from immune recognition

A protein found in the virulent avian influenza virus strain called H5N1 forms tiny tubules in which it “hides” the pieces of double-stranded RNA formed during viral infection, thus preventing antiviral immune response from infected cells, according to researchers at Baylor College of Medicine (BCM), the United Sates.

Two domains of the protein NS1 combine to form tiny “tubules” in which double-stranded RNA is hidden from the immune system, said Dr. B.V. Venkataram Prasad, a BCM professor, and Dr. Zachary A. Bornholdt, his student, now at the Scripps Research Institute. “Once we confirm the importance of this structural information, we should be able to design drugs to block this action,” said Dr. Prasad. The two researchers had earlier recognized the importance of NS1 in the virulence of influenza viruses, particularly H5N1, a form of avian flu associated with more than half the deaths in a 2004 bird flu outbreak. They described the structure of an area of the protein called the effector domain. In the current study, the two scientists “crystallized” the entire protein. By doing this, they were able to determine its structure using X-ray crystallography. This technique and cryo-electron microscopy enabled scientists to determine the 3D structure of proteins.

That structure revealed a previously unsuspected idiosyncrasy of NS1 in H5N1 that could explain the virus’ virulence. In most cases, when an infected cell is exposed to a virus, double-stranded RNA molecules are formed triggering a potent anti-viral response that involves production of interferon. However, the two domains of NS1 in this H5N1 interact to form tiny tubules. The double-stranded RNA is hidden or sequestered in these structures. The cell never sees a significant length of the RNA and does not marshal its immune forces to the fight the virus. The scientists believe also that cellular factor binding sites found on the surface of the tubules also play a role in fooling the immune system.


New enzyme may revolutionize production of plastics

In future, polymethyl methacrylate (PMMA, better known as acrylic glass) could be made in an environmentally friendly way using natural raw materials such as sugars, alcohols or fatty acids. PMMA is manufactured by polymerizing methyl methacrylate (MMA). Scientists at the University of Duisburg-Essen and the Helmholtz Centre for Environmental Research, both in Germany, have found in a bacterial strain an enzyme that could be used for the biotechnological production of a precursor of MMA.

The new enzyme called 2-hydroxyisobutyryl-CoA mutase, discovered by Dr. Thore Rohwerder and Dr. Roland H. Müller, enables the branching of a linear C4 carbon structure. Compounds of this type are precursors of MMA. The revolutionary aspect is that this enzyme, integrated into metabolically appropriate micro-organisms, can also transform sugars and other natural compounds into the products desired. Until now, the only way to produce this precursor – 2-hydroxyisobutyrate (2-HIBA) – was a purely chemical process based on petrochemical raw materials.

The chemicals industry worldwide is searching for suitable biological processes, so that in future, renewable raw materials can also be used as a basis for MMA synthesis. The mutase presented here provides the solution: an enzyme that shifts a functional group from one position to another within a molecule.



A little protein for a big problem

Sarcospan, an overlooked and undervalued protein, has got its moment in the spotlight. Ms. Angela K. Peter and colleagues at the University of California-Los Angeles, the United States, has shown that adding it to muscle cells might ameliorate the most severe form of muscular dystrophy. In Duchenne muscular dystrophy (DMD), the mutated dystrophin protein fails to anchor correctly to its membrane glycoprotein complex. Without this anchoring, muscle cells experience contraction-induced damage. Sarcospan’s structure suggests that it might stabilize the membrane complex, the scientists decided to test the effects of increasing sarcospan expression in a DMD mouse model.

Instead of improving the dystrophin-glycoprotein interaction, the increased sarcospan coaxed a dystrophin relative called utrophin to spread out on the muscle membrane. Utrophin is normally restricted to the neuromuscular junction, where it serves a role similar to that of dystrophin. The extra sarcospan prompted higher levels of utrophin in the cell, but not by increasing its expression. It instead stabilized extra-junctional utrophin complexes, which normally form early in development and then disappear after the first few weeks. The true importance of this discovery will lie in its potential for human therapeutics, specifically gene therapy, considering sarcospan’s small gene size (600 bp) that would allow easy packaging into the safest viral vectors.




A DNA-based vaccine shows promise against avian flu

New research by scientists in the United States and Taiwan province of China has led to a vaccine with the potential to stop most strains of H5N1 flu viruses in their tracks, as demonstrated in mice. Prof. David D. Ho, Scientific Director of the Aaron Diamond AIDS Research Centre, New York, along with his colleagues at Taiwan’s Academia Sinica, built the vaccine using DNA rather than dead virus particles grown in chicken eggs. Such a vaccine, comprising plasmid DNA that has been genetically modified to elicit specific immune responses, is much easier and faster to modify and produce – critical advantages when facing an epidemic.

Because H5N1 viruses are incredibly diverse and mutate fast, Prof. Ho and his collaborators first created a consensus sequence that incorporated all of the conserved parts of the gene encoding the virus’s outer protein. To deliver it, a point where DNA vaccines often fail, the researchers turned to electroporation, a technique that helps increase uptake of the vaccine. By combining their consensus-sequence vaccine with a small electric stimulus, the researchers found that their mouse subjects responded with an incredibly broad immune reaction.

“It could be that the vaccine in its current form could protect against most of the H5N1 viruses out there,” says Prof. Ho. Even if it can’t, he notes, if a different strain of H5N1 begins to circulate, it should only take a few days to obtain its genetic sequence and adapt the existing vaccine to fight it. A version of the consensus vaccine is already being produced, so that it can move into human clinical trials as quickly as possible.



Chemical from medicinal plant helps fight HIV

Like other kinds of cells, with age, immune cells lose the ability to divide because a part of their chromosomes known as a telomere becomes progressively shorter with cell division. As a result, the cell changes in many ways, and its disease fighting ability is compromised. A new study by University of California-Los Angeles AIDS Institute study has found that a chemical from the root of Astragalus, used in Chinese herbal therapy, can prevent or slow this progressive telomere shortening, which could make it a key weapon in the fight against HIV. The researchers say that the chemical TAT2 has the potential to supplement or even replace the ‘highly active anti-retroviral therapy’, which some patients do not tolerate well and is expensive.

Generally, the telomeres in cells are sufficiently long that they can divide many times without a problem. Moreover, when fighting infections, T-cells – a lymphocyte that plays a central role in cell-mediated immunity – can turn on an enzyme called telomerase, which can prevent the telomeres from shortening. However, when dealing with a virus that can’t be fully eliminated from the body, such as HIV, the T-cells fighting the virus can’t keep their telomerase turned on forever.

The researchers tested TAT2 in several ways. First, they exposed the CD8 T-cells, the “killer” T-cells that help fight infection, from HIV-infected persons to TAT2 to find that the chemical not only slowed the shortening of the telomeres but improved the cells’ production of soluble factors called chemokines and cytokines, which had been previously shown to inhibit HIV replication. The scientists separated out the CD8 T-cells and the CD4 T-cells in blood samples from HIV patients. They treated the CD8 T-cells with TAT2 and combined them with the CD4 T-cells in the dish to find that the treated CD8 cells inhibited production of HIV by the CD4 cells.



A vaccine type with potential to protect against TB

Researchers are a step closer to finding a vaccine that better protects against tuberculosis (TB). An experimental vaccine for TB tested at St. Louis University (SLU), the United States, appears likely to offer significantly better protection against the potentially fatal disease than the standard TB vaccine called Bacille Calmette-Guérin (BCG). “Not only was it as safe as the standard vaccine, it induced a better immune response, which suggests it will be more effective at protecting against tuberculosis,” said Dr. Daniel Hoft, Director of the Division of Immunobiology at SLU’s School of Medicine, who led the study.

The investigational vaccine is made from a weakened TB germ line from one of the strains of the current TB vaccine, which was created more than 75 years ago. The new recombinant vaccine uses an antigen to help focus the immune system on blocking aggressive and deadly TB organisms. In this Phase I clinical trial, researchers vaccinated 35 study participants. BCG vaccine was given to 17 study participants, while the other 18 received the investigational recombinant BCG vaccine. Researchers compared five immune functions induced by the vaccines and found that the investigational vaccine induced more powerful responses against the disease. The investigational vaccine also was safe and well tolerated. The study thus demonstrated that the concept of using a recombinant vaccine holds promise as a better protection for people against TB.



Key trigger of embryonic stem cell differentiation in new light

Clusters of mouse embryonic stem (ES) cells called embryoid bodies more closely approximate true embryos in organization and structure than previously thought, according to researchers at the Stanford University School of Medicine, the United States. Harnessing the signals that influence the cells’ fate may help researchers more accurately direct the differentiation of ES cells for use in therapy.

The researchers found that embryoid bodies have hallmarks of gastrulation – a remarkable developmental step that launches a hollow ball of cells towards becoming an organism with three distinct types of precursor cells. They showed that this process is initiated by a single signalling pathway in embryoid bodies and in real embryos. Enhancing or blocking this signal affects what the cells become, the scientists found.

The researchers used easily tracked reporter genes, which are expressed only when cells are responding to Wnt signals, to figure out when and where Wnt is active in mouse embryos and embryoid bodies. Using this system, they learned that Wnt-responsive cells first appear in 6.5-day-old embryos in an area called the primitive streak that forms on what will become the posterior side of the embryo. It is the first step towards gastrulation, wherein an outer layer of cells dimples inwards at what will be either the mouth or anus to form the three distinct precursor cell types shared by most animals: the ectoderm, the endoderm and mesoderm.

Wnt-responsive cells in the embryoid bodies also spontaneously form a primitive streak, though they never truly gastrulate. Supplementing the naturally occurring Wnt signal with “extra” Wnt protein accelerated the formation of the primitive streak, while adding proteins that blocked Wnt activity inhibited it. The extra Wnt caused the Wnt-responsive cells to differentiate primarily into mesendodermal precursors (which can become either mesoderm or endoderm) and inhibited the formation of neurectoderm (ectoderm destined to become cells of the nervous system). Blocking Wnt activity tipped the balance in the other direction, causing the cells to shun mesendoderm and become mainly neurectoderm. The researchers also identified one specific factor, called bmp, that triggers the cells’ Wnt-responsive pathways. Inhibiting this factor stops the spontaneous formation of the primitive streak in the embryoid bodies.


Scientists coax brain cells in mice to regenerate

Dr. Zhigang He and colleagues at the Children’s Hospital, Boston, the United States, have found a way to get damaged nerve cells in the brains of mice to repair themselves – a finding that may offer new treatments for spinal cord and brain injuries. Turning off proteins that keep nerve cell growth in check allowed the scientists to stimulate regrowth in mice with damaged optic nerves.

Meanwhile, another team at Genentech Inc. found that blocking a protein that hinders cell repairs allowed nerve cells to regenerate in vitro. The two findings together offer important leads on ways to coax damaged nerves in the brain and spinal cord to fix themselves. The studies focused on nerve fibres called axons that carry electrical signals throughout the body.

Dr. He’s team focused on a gene network called the mTOR pathway, which is very active when young nerve cells are first growing but becomes less active once nerve cells mature. Nerve injury appears to shut down this network completely. Two proteins – PTEN and TSC1 – appear to be responsible for silencing this pathway, the team discovered. “If we get rid of those proteins, axons can regenerate very dramatically,” Dr. He said. Mice genetically engineered to lack the proteins kept more neurons after an injury to the optic nerve than normal mice, and the mutant mice were able to grow new axons within two weeks.


Key HIV protein points to more powerful AIDS drugs

In the United States, scientists at University of Michigan have provided the most detailed picture yet of a key HIV accessory protein that foils the body’s normal immune response. Based on the findings, they are searching for new drugs that may someday allow infected people to be cured. “There is a big hole in current therapies, in that all of them prevent new infection, but none attack the cells that are already infected and hidden from the immune response,” says Dr. Kathleen L. Collins, the study’s senior author.

The study details the complex actions of a protein, HIV-1 Nef, that is known to keep immune system cells from doing their normal jobs of detecting and killing infected cells. Dr. Collins and her team showed how Nef disables two key immune system players – major histocompatability complex 1 proteins (MHC-1) that present HIV antigens to the immune system, and CD4, the cell-surface receptor that normally locks onto a virus and allows it to enter the cell – inside an infected cell.

By pushing the MHC-1 proteins into an infected cell’s “trash bin” so that they fail to alert the T cells, Nef’s actions allow active virus to hide and reproduce. Once a cell has been infected, Nef destroys CD4. The result is that this encourages new virus to spread to uninfected cells. Nef’s activities are variable and complex. But the research team’s findings suggest that the many pathways involved may end in a final common step. That could make it possible to find a drug that could block several Nef functions.



Hybrid rice developed for salt-encrusted land

Mr. Zhu Peikun, a scientist from Shenzen, China, says he has developed a strain of rice that thrives in salt-encrusted lands. He crossed cordgrass with rice to create a hybrid rice strain that can tolerate high levels of salt in the soil. The hybrid rice strain was tested in the east coast province of Shandong, the second most populated province in China. Based on the results, Mr. Zhu said, the hybrid rice could yield as much as 874 tonnes per acre. As much as 75 per cent of China’s arable land is salina, or land encrusted with salt, he said.


An essential gene for forming ears of corn

Dr. David Jackson at the Cold Spring Harbour Laboratory, the United States, and a team of plant geneticists have identified a gene essential in controlling development of the maize (corn) plant. The new research extends the growing biological understanding of how the different parts of maize arise – important information for a plant that is the most widely planted crop in the United States and a mainstay of the global food supply.

The researchers found that a gene called sparse inflorescence1, or spi1, is involved in the maize plant’s synthesis of the growth hormone auxin. This chemical messenger is produced by the tip of a growing shoot. When the hormone is applied to only one side of the shoot, that side grows faster, causing the tip to bend. In a more complex process, auxin also helps to shape structures such as leaves or the female organs (ears) and male organs (tassels) of corn. The initial stages of these structures are called meristems, which consist of versatile, undifferentiated cells analogous to the stem cells found in animals.

Dr. Jackson and his colleagues from University of California San Diego, California State University and Pennsylvania State University, discovered that meristems emerge from an interplay between the synthesis of auxin by various cells and its motion between them. Disrupting either its production (by causing a mutation in the spi1 gene) or its motion results in stunted, defective organs.

“In maize, spi1 mutations cause severe developmental effects,” Dr. Jackson said. The work helped demonstrate that spi1 in maize has evolved a crucial role in auxin biosynthesis, and is essential for what plant scientists call inflorescence development – the process in seed plants in which a shoot forms that supports the plant’s flowers.



Olive stones could yield biofuel

Scientists have discovered that olive stones can be turned into bioethanol, a renewable fuel that can be used as an alternative to petrol or diesel. The development gives the olive processing industry an opportunity to make profitable use of the four million tonnes of olive stones it generates every year. The process was developed by scientists from the Universities of Jaén and Granada in Spain.

“The low cost of transporting and transforming olives stones make them attractive for biofuels,” said researcher Mr. Sebastián Sánchez. The olive stone, produced in processing of olive oil and table olives, makes up around a quarter of the total fruit. It is rich in polysaccharides that can be broken down into sugar and then fermented to produce ethanol.


Scientists develop cancer-fighting tomato

A purple tomato genetically engineered to contain nutrients more commonly seen in dark berries helped prevent cancer in mice, British researchers have reported. Cancer-prone mice fed the modified fruit lived significantly longer than animals on a standard diet with and without regular tomatoes, according to Prof. Cathie Martin and colleagues at the John Innes Centre, United Kingdom. “The effect was much bigger than we had expected,” said Prof. Martin, a plant biologist.

The study focused on anthocyanins, a type of antioxidant found in berries such as blackberries and blackcurrants that have been shown to lower risk of cancer, heart disease and some neurological diseases. Using genes that help colour the snapdragon flower, the researchers discovered they could get the tomatoes to make anthocyanins – turning the tomato purple in the process.

Mice genetically engineered to develop cancer lived an average of 182 days when they were fed the purple tomatoes, compared with 142 days for animals on the standard diet. The researchers cautioned that trials in humans are a long way off and the next step is to investigate how the antioxidants actually affect the tumours to promote better health.



Research on plant viruses may lead to improved crop yields

An inter-disciplinary group of scientists has obtained the first detailed information about the structure of the most destructive group of plant viruses known – flexible filamentous viruses. The cost of worldwide crop losses due to plant diseases is estimated at US$60 billion annually. The 300-plus species of flexible filamentous viruses are responsible for more than half of all virus damage. “Their flexibility makes them very difficult to analyse,” says Prof. Gerald Stubbs at Vanderbilt University, the United States, who directed the study.

Besides scientists from Vanderbilt, the five-year project had the participation of researchers from the Department of Energy’s Brookhaven National Laboratory and Argonne National Laboratory, Boston University, Illinois Institute of Technology and University of Kentucky. The result of this effort was determination of the low-resolution structures of two flexible filamentous virus species – soybean mosaic virus and potato virus X. The researchers found that the external protein coats of the two viruses are extremely similar although they come from two different viral families, Potyviridae and Flexiviridae. The exchange of genes between different viruses is a well-known phenomenon and usually takes place when two viruses invade the same host, Prof. Stubbs says.

Some potential applications of the research results include engineering molecules based on the viral structure that interfere with the viruses’ ability to infect plants. Another possibility would be to introduce modified versions of viruses or to coat protein genes into a plant to protect it from viral and insect attacks. Yet another possible application would be to use modified viruses to introduce genes that instruct plants to make other useful products – for example, antibiotics or other drugs.



A gene that may contribute to improved rice yield

A team of researchers, including Pennsylvania State University Distinguished Professor of Biology Dr. Hong Ma, has identified a gene in rice that controls the size and weight of rice grains. The gene may prove to be useful for breeding high-yield rice and, thus, may benefit the vast number of people who rely on this staple food for survival.

The researchers first searched for and identified mutant strains of rice that exhibited underweight grains. They found a mutant that is defective in its ability to produce normal-sized grains, says Prof. Zuhua He, a biologist at the Chinese Academy of Sciences and the leader of the team. The group then examined the mutant and found that it carried a mutation within the GIF1 gene responsible for controlling the activity of the enzyme invertase, which converts sucrose to substances that then are used to create starch.

Next, to test the ability of the GIF1 gene to control the production of invertase, the team measured the activity of invertase within a normal strain of rice, in which the GIF1 gene lacked any mutations, and within a mutant strain of rice, in which the GIF1 gene contained a mutation that caused a defect in the invertase activity. The scientists found that invertase activity in the mutant strain was only 17 per cent of the activity that was seen in the normal strain, suggesting that the GIF1 gene does control invertase activity.

The team then created a transgenic lines of rice in which the GIF1 gene was overexpressed and found that, compared with normal strains, the transgenic rice had larger and heavier grains. It also found that the GIF1 gene is one of the genes that were selected during the domestication of rice. The scientists hope that their findings will help others to create hybrid varieties of rice that produce even larger grains.




Colloidal Nanoparticles in Biotechnology

In this publication, Dr. Abdelhamid Elaissari, an internationally respected author and researcher, reports on and analyses a broad range of major findings from new studies on the use of colloidal nanoparticles in biomedical, food and environmental diagnostics and analyses. Throughout the presentation, the book uses a blend of classical tools, including optical microscopy, atomic force microscopy, microsystems and microfluidics, to help the reader have full knowledge of colloidal nanoparticles for research and applications.

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Nutrigenomics and Proteomics in Health and Disease

Nutrigenomics and Proteomics in Health and Disease: Food Factors and Gene Interactions aims to compile the current science based upon nutrigenomics and proteomics in food and health. Coverage includes many important nutraceuticals and their impact on gene interaction and health. Authored by a stellar international team of multi-disciplinary researchers, the publication acquaints food and nutrition professionals with these new fields of nutrition research and conveys the state of the science to date. Several chapters are devoted to genomics/proteomics and specific disease and health conditions. The heart of the book focuses on food factors-gene interaction, covering lipids; proteins, amino acids and peptides; carbohydrates; carotenoids; phytochemicals; prebiotics and probiotics; and minerals.

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