VATIS Update Biotechnology . Sep-Oct 2010

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Biotechnology Sep-Oct 2010

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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Genetically modified crops are increasing steadily

From 1996 to 2009, genetically modified (GM) crops planted have seen an 80 fold increase. In 2009, 14 million farmers in 25 countries planted 330 million acres of biotech crops, according to the International Service for the Acquisition of Agri-Biotech Applications (ISAAA). In 2009, the acreage showed a 7 per cent increase (22 million acres) from 2008.

Among all the soybeans grown in the world as of 2009, three-quarters were GM crops, as was half of the cotton, one-quarter of corn and one-fifth of canola. Of the various GM traits, herbicide tolerance was in 62 per cent of the crops planted, according to ISAAA. It was also noted that 21 per cent of the biotech crops included “stacked traits”, or more than a single trait. The United States leads the world in biotech crop production compared with other countries. The figures for 2009 (in million hectares) biotech crop production were: the United States 64.0, Brazil 21.4, Argentina 21.3, India 8.4, Canada 8.2, China 3.7, Paraguay 2.2 and South Africa 2.1.

Biotechnology: improving quality of life

Biotechnology, earlier limited to agriculture, has now expanded to other fields such as medicine and energy. From discovery of drugs to determining methods of drug usage, biotechnology plays an important role. Genetic diseases and other illnesses such as hepatitis B, hepatitis C, cancer, arthritis, haemophilia, bone fractures, multiple sclerosis and cardiovascular disorders can be treated using biotechnology. With its aid, effective and inexpensive medicines can be manufactured.

Another branch of biotechnology is genetic testing, which has helped researchers in decoding DNA, studying its structure and so forth. Prenatal diagnostic screening, cancer screening and carrier screening are facilitated by genetic testing. Forensic labs are now equipped with the latest devices and testing equipment that help resolving criminal cases. Many experiments and clinical studies undertaken have thrown more light on DNA, RNA and other such complex molecular structures.

Biotechnology also helps in the conservation and protection of environment. An ever-increasing demand for fuel has caused depletion of oil resources. Biotechnology has spurred the evolution of biofuels that are derived from sugarcane, plant vegetable oils, animal fats as well as recycled greases, thereby providing a cleaner and greener environment.

With each passing day, biotechnology with its innovations and applications improves quality of human life. Over-dependence on natural resources, environmental degradation and other issues that are grappling the world today are steadily being resolved. With better medicines, finer treatments and sophisticated medical centres, the average life expectancy has also increased. In a nutshell, biotechnology has widened the horizons of modern science and improved every aspect of human life.

Monsanto explores partnerships with India on biotech traits

The Indian arm of the global seeds and agrochemicals giant Monsanto is holding talks with the Indian government to offer biotechnology traits like weed control, tolerance to moisture deficient and nitrogen application in varietal crops like wheat, sugarcane, mustard and soybean. “We are in the explorations stage and talks are in initial stages with the central government though we are yet to approach states. We are focused on R&D in seed and biotech product innovation in cotton, corn, wheat, sugarcane and soybean, all of which are relevant to enhancing productivity in India,” explained Mr. Jagresh Rana, Director, Mahyco Monsanto Biotech, India. Varietal crops are those where the farmer can reuse the old seeds for re-cultivation. Currently, the global major doesn’t have any partnerships in varietal crops, as their hybrids can’t be created and hence has not found viable business models in them. “Hence, we are looking for public private partnerships in these. We are willing to dialogue on appropriate go-to-market models,” Mr. Rana added.

To innovate and discover biotechnology traits like increased tolerance to less moisture or draught-tolerance trait in soybean or lesser application of nitrogen in wheat and reduce insect damages, the company will need to invest more than Rs 5 billion (US$110 million) over a decade and this can happen with the support of government, Mr. Rana said. He explained that there are business models for companies like Monsanto where hybrids can be created, like in cotton and corn, and the farmer has to buy fresh seeds every season. In 2009, the company entered and expanded into new partnerships with six state governments – of Gujarat, Rajasthan, Himachal Pradesh, Orissa, Karnataka, and Jammu and Kashmir – to help increase crop productivity through better hybrids seeds in corn, cotton and vegetables.

Biotechnology boosts healthcare in Viet Nam

The great progress that Viet Nam has made in biotechnology can help improve its healthcare system, says a report of the Sai Gon Hi-Tech Park. The report, by Dr. Thai Nguyen, Chief Scientist at the Park’s Biotech Division, points out that Viet Nam has achieved the critical mass required for international standard and multi-disciplinary biotechnology research and development. The country also has the conditions and resources required to elevate biotechnology into a major industry, it says.

NanoGen Inc., which has been in existence for almost 10 years, makes monoclonal antibodies for cancer treatment for the local and international markets. Vabiotech Corp. has successfully used the reverse genetic approach for making recombinant vaccine for hepatitis B. Stem cell research is going on at various places, though most of it is currently at basic level. At the Natural Science University, Dr. Ngoc K. Phan has done pioneering work in setting up various embryo and adult stem-cell banks for conducting clinical studies and eventually treating patients. Last year, the Viet Nam Gene Therapy Centre was established at Bach Mai Hospital, the country’s pre-eminent public medical facility. Nanotechnology has begun to be applied in biotech areas like gene isolation and purification.

Many biotech centres receive assistance from international centres and collaborate with them. These include the Asia-International Molecular Biology Network and Global Health Sciences of University of California, the United States. A team from the United Kingdom’s Oxford University set up the Oxford Clinical Research Unit in association with Viet Nam’s Tropical Diseases Hospital to investigate major medical issues using pathological samples from local populations.

The report also identifies the tasks that need to be done to develop biotechnology in Viet Nam – like increasing international collaborations and partnerships and developing strong information-based research – and the challenges facing the industry like lack of funds for developing infrastructure.

Kenya’s cotton production set to increase six fold

Kenya is awaiting the Biosafety Act before Bt cotton can be produced on large scale. Among other things, the law will allow the commercialization of genetically modified (GM) cotton. Kenya will become the third African country to grow GM cotton after South Africa and Burkina Faso, and the first to commercialize it in Central and East Africa. According to Dr. Charles Waturu, Director of the Thika Centre of Kenya Agricultural Research Institute (KARI), this will step up cotton production from 50,000 bales per year to 300,000 bales and meet the country’s cotton deficit. Already, the taskforce formed to spearhead the commercialization of GM cotton has proposed that 100,000 acres be kept aside to kick-start the project.


Merck buys vaccine unit from Hawaii Biotech

In the United States, Merck & Co. has agreed to purchase bankrupt Hawaii Biotech’s dengue fever vaccine unit for an undisclosed sum. It is a critical move for Hawaii, which filed for bankruptcy protection last year. The sale leaves Hawaii with a West Nile virus vaccine in development. Hawaii CEO Mr. Elliot Parks said Merck’s interest in the dengue unit validates the work his company has done on the programme. “They clearly have the resources to get the products registered and into the public health system,” he noted. Merck said that the purchase is part of its strategy to develop vaccines for unmet medical needs. The vaccine will enter the clinic later this year.

International Stem Cell Corp. to set up European subsidiary

The International Stem Cell Corporation (ISCO), the United States, has signed a Memorandum of Understanding (MoU) with ARG Vermogensverwaltung AG, a German Investment Fund, to create a new European subsidiary to be funded with up to US$10 million of capital derived from ARG as well as other independent sources in Europe. ISCO Europe will be licensed by ISCO to develop and market therapeutic products derived from ISCO’s technology across Euro currency countries and Switzerland. New technologies developed by ISCO and ISCO Europe will be made mutually available. ISCO develops human parthenogenic stem cells derived from unfertilized human eggs.

ISCO is expected to own about 80 per cent of its subsidiary, which will be listed at the Deutsche Borse. ISCO Europe’s shares will not be convertible into ISCO shares on any United States exchange. With the construction of its European subsidiary, ISCO wants to gain access to new capital as well as to new scientific input. “We are creating an investment, research and development, marketing and distribution entity by adding capital and human resources from Europe to help fulfil ISCO’s goal of supplying its proprietary cells and cell therapies to the world,” said Mr. Kenneth Aldrich, Chairman of ISCO.

Camson Biotech plans joint ventures in three countries

Camson Biotechnologies, an Indian agricultural biotechnology firm, plans to set up joint ventures in three countries. “Our innovative R&D-led approach to farming and agriculture inputs has seen international interests and we are setting up business in Singapore, Dubai and Cairo in Egypt to meet the growing demand for zero residue agri-inputs,” said Mr. Dhirendra Kumar, the Managing Director of Camson Biotech. The company will be setting up manufacturing and distribution units in all three locations. These cities are strategically chosen to give Camson a central geographical presence and cater to surrounding countries to meet the increasing demand for food and agricultural products, Mr. Kumar said.

Camson Biotech has combined latest knowledge of breeding, molecular genetics and metagenomics in agriculture with the latest practices in environmental safety and protection to market a wide range of products that include hybrid seeds, biofertilizers and biocides that are non-toxic, eco-friendly and residue-free.

Intellect gets patent allowance for Alzheimer’s vaccine

Intellect Neurosciences Inc., a biopharmaceutical company in the United States, has received a Notice of Allowance from the United States Patent and Trademark Office related to RV01 and RV02, the Company’s two lead vaccine candidates. The Notice of Allowance is a written communication stating that the patent application has been allowed and will be granted as a new patent. RV01 and RV02, generated using Intellect’s RECALL-VAX technology, have the potential to delay the onset of or prevent Alzheimer’s disease in individuals susceptible by age, genetic or other risk factor. Patents previously have been issued in Europe, Australia, New Zealand and South Africa, and are pending in Canada and Israel.

“This new patent should increase interest from potential strategic partners to collaborate with Intellect on the RECALL-VAX programme,” commented Dr. Daniel Chain, Chairman and CEO of Intellect. The company had presented the first animal data regarding RECALL-VAX in August 2007. “This vaccine could achieve the goal of a safe immunotherapy for Alzheimer’s disease, providing prevention in at-risk populations,” Dr. Chain said.

Merck and Alectos Therapeutics in new collaboration

Undaunted by the mixed results trying to come up with a new therapy for Alzheimer’s disease, Merck & Co., the United States, has finalized a US$289 million deal with Alectos Therapeutics of Canada to collaborate on new molecules for the memory-wasting ailment and other disorders. Like other developers, Merck has experienced plenty of frustration trying to develop new therapies for the disease, an incredibly elusive target that afflicts a steadily growing number of seniors.

The collaboration will target the compounds that modulate O-linked N-acetylglucosaminidase, an enzyme that is believed to be involved in the development of Alzheimer’s disease. “This is an important validation of our scientific leadership in this area and we look forward to working with Merck to realize the full value of this novel mechanism for a range of neuroscience disorders,” said Mr. Ernest McEachern, the CEO of Alectos. The pact includes an upfront payment as well as milestones.

A*STAR ties up with Cytos Biotechnology for flu vaccine

The Agency for Science, Technology and Research (A*STAR) of Singapore and Cytos Biotechnology of Switzerland have jointly announced their first collaboration on a virus-like particle (VLP) vaccine. This partnership – which involves academic and clinical partners across Singapore – aims at research, development and commercialization of a VLP vaccine to manage influenza infections. It could potentially secure an independent supply of vaccines for Singapore and other countries in the region to protect against seasonal influenza and future pandemics and extends Cytos’ R&D pipeline.

Under the agreement, Cytos Biotechnology will work with A*STAR’s Experimental Therapeutics Centre (ETC) and Singapore Immunology Network (SIgN) to develop and produce a VLP-based vaccine targeting influenza haemagglutinin protein. The vaccine candidate will then be further evaluated in pre-clinical safety and efficacy studies by DSO National Laboratories, Singapore. Duke-NUS Graduate Medical School Singapore and the Singapore Clinical Research Institute will then conduct a proof-of-concept study to evaluate the safety of the vaccine and its capacity to induce virus-neutralizing antibodies (HI titres). Thereafter, Cytos will hold worldwide, sub-licensable right to further develop, manufacture and commercialize the vaccine, while A*STAR subsidiaries will be entitled to produce the vaccine for the Association of Southeast Asian Nations (ASEAN), including Singapore. A*STAR subsidiaries can earn royalty on worldwide net sales from influenza vaccine products developed according to the terms of this agreement.

Prana Biotechnology secures patents for its pharmaceuticals

Prana Biotechnology Ltd., Australia, focuses on commercializing research on Alzheimer’s disease and other major age-related neurodegenerative disorders. In line with this, the company has now secured key patents in Europe and the United States for select PBT2 (a second-generation 8-hydroxy quinoline analog) compositions.

The United States Patent and Trademark Office (USPTO) granted Prana a composition of matter patent titled ‘8-Hydroxyquinoline derivatives’ for selected 8-hydroxyquinoline compounds, including its lead clinical asset, PBT2. It also extended the term of the PBT2 patent for another 2½ years, with a set expiration date of 21 December 2025, which could later be extended.

In the case of Europe, the mandatory nine-month post-grant opposition to its patent application has expired now, releasing the company from any third-party objections regarding the patent. The case has been placed at present on the Register of European patents, with a 20-year expiration date set for 16 July 2023, with a possible extension of term of up to five years.


Scientists pinpoint 95 gene loci linked to lipid metabolism

Along with their colleagues from the Global Lipids Genetics Consortium, scientists of Helmholtz Zentrum München (HZM), Germany, have found 95 gene loci in the human genome. Each of these loci is associated with at least one of the four most important factors of lipoprotein metabolism: total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides.

The study focused on two key questions. First, are there really genes on these loci that directly influence lipoprotein metabolism? Second, do they have any significance for possible therapy approaches? The scientists were able to answer both questions with a clear yes. Professor Thomas Meitinger, Director of the HZM Institute of Human Genetics, which also participated in the study, said: “Closer scrutiny of the gene loci revealed genetic variants which we know offer a molecular target for cholesterol-lowering drugs. That means that these genetic variants raise the potential for new target structures and thus new therapeutic approaches.” Data from 46 genome-wide association studies including more than 100,000 individuals were used in this meta-analysis. One important data source was HZM’s population-based study, cooperative health research in Augsburg region (KORA). The scientists used a variety of methodical approaches. For instance, they compared more than 2.5 million DNA building blocks from population groups of European and non-European origin, analysed genetic variants of patients with extreme lipid concentrations and confirmed some of their own findings from the genome-wide analysis in mouse models.

Antiviral gene helps suppress cross-species spread of HIV

A study in the United States by Dr. Andrea Kirmaier and Dr. Welkin Johnson of Harvard Medical School, together with Dr. Vanessa Hirsch of the National Institutes of Health, has provided direct evidence in apes and monkeys of a restriction factor gene called TRIM5 acting as a genetic barrier to cross-species transmission of a primate immunodeficiency virus related to the human immunodeficiency virus HIV-2.

Primate immunodeficiency viruses include HIV-1 and HIV-2, as well as the numerous simian immunodeficiency viruses (SIVs) found among African apes and monkeys. The distribution of SIVs among their natural hosts has a long history of viruses jumping between species, including the very recent invasions of humans by SIVs from chimpanzees, giving rise to HIV-1, and from sooty mangabey monkeys, giving rise to HIV-2. Scientists believe that the movement of viral pathogens between hosts ultimately drove the evolution of certain genes, called restriction factors, as protection against such events.

Expression of one such gene, TRIM5, renders cultured cells resistant to infection by retroviruses such as HIV-1 and HIV-2 in the laboratory. The new study confirms the ability of TRIM5 to suppress cross-species transmission of SIV in vivo. Dr. Kirmaier and colleagues took advantage of the fact that rhesus macaques have several TRIM5 versions (or alleles) in their gene pool. Hence, different macaques will harbour different TRIM5 versions, leading to the prediction that individual macaques will differ in their sensitivity to infection by viruses from other species. The investigators showed that SIVsm, a virus found naturally in sooty mangabeys, is inherently blocked by some but not all TRIM5 alleles found in rhesus monkeys.

The team also found a correlation between the combination of TRIM5 variants present in each individual rhesus monkey in the study and whether that monkey had high or low levels of SIVsm virus growing in its blood. Importantly, the same TRIM5 alleles that blocked SIVsm infection in laboratory were also present in those monkeys that had the lowest levels of SIVsm infection, and vice versa. This evidence firmly establishes what was suspected from the prior cell culture studies – TRIM5 plays a role in suppressing replication of the virus in the new host. From a practical standpoint, variation of genes like TRIM5 in rhesus monkey may be highly relevant to the central role these animals play as models for studying acquired immunodeficiency syndrome (AIDS) and vaccines against AIDS.

Gene’s role in a lifetime of memories

Researchers at St. Jude Children’s Research Hospital, the United States, showed that a gene named Prox1 is a key player in the normal development of a brain structure crucial for learning and memory, and that it remains active throughout life, nurturing the cells vital for making new memories. This study focused on a small region of hippocampus known as dentate gyrus, a brain structure needed for memory and learning that is home to the sub-granular zone where the neural stem cells destined to become granule cells are housed. This is the first report detailing Prox1’s function in dentate gyrus.

Researchers showed that the dentate gyrus fails to develop properly when Prox1 is removed at different stages of mouse development. They also demonstrated that Prox1 remains important throughout mammalian life to ensure production of new granule cells, which are needed to form new memories. The findings raise the possibility that subtle mutations in Prox1 might be linked to memory and learning problems, said the paper’s senior author Dr. Guillermo Oliver from the Department of Genetics and Tumour Cell Biology. In the study, the investigators determined that Prox1 is active in the adult mammalian brain during a particular stage of differentiation when neural stem cells change from cells of unlimited potential to more specialized granule cells. The scientists reported that in the dentate gyrus, Prox1 is produced by intermediate progenitor cells and that the lack of Prox1 results in death of these intermediate cells. Without these intermediate progenitor cells, new adult granule cells do not develop. The researchers also linked Prox1 to a feedback mechanism that signals stem cells to stop differentiating.

Genome structure linked to developmental diseases

In the United States, a team of researchers from Whitehead Institute, Massachusetts Institute of Technology (MIT), University of Massachusetts and University of Colorado has discovered that each cell type in the human body has a unique genome structure, which is due to a newly discovered mechanism that controls the genes. The protein complexes that create this genome structure play a pivotal role in regulating gene transcription and cell state, and have been implicated in multiple developmental diseases.

“I think we have a fundamental new insight into the underlying causes of several neurological and developmental diseases, including Opitz-Kaveggia syndrome, Lujan syndrome and Cornelia de Lange syndrome,” says Whitehead Institute Member Dr. Richard Young. According to the paper from Dr. Young’s lab, a DNA loop formed at the beginning of cell-type-specific genes enables activation of these genes. Each cell type has its own gene expression programme to maintain its cell state. For gene activation, regulatory factors and gene expression machinery bound to two different parts of the DNA, called the promoter and the enhancer, must come in contact. This contact, which is facilitated and maintained by protein complexes called Mediator and Cohesin, forms a set of DNA loops that is specific to each cell type.

That is a big surprise, says Dr. Young, whose lab is deciphering the overall cellular circuitry required to regulate gene expression and cell state. The scientists didn’t expect that the DNA loops are formed by Mediator and Cohesin at active cell-type-specific genes. Problems with this DNA loop structure can interfere with the activation of cell-type-specific genes, which can cause the cell to lose its normal state. Mutations in Mediator and Cohesin can cause various developmental syndromes and diseases.

Influence of Vitamin D on genes linked to diseases

Recent research has dramatically highlighted the extent to which vitamin D deficiency may increase susceptibility to a wide range of diseases. Scientists have mapped the points at which vitamin D interacts with human DNA, and identified over 200 genes that it directly influences. They used new DNA sequencing technology to create a map of vitamin D receptor binding across the human genome. The vitamin D receptor, a protein activated by vitamin D, attaches itself to DNA and thus influences what proteins are made from human genetic code.

Led by Dr. Sreeram Ramagopalan from Wellcome Trust Centre for Human Genetics in the United Kingdom, the researchers found 2,776 binding sites for the vitamin D receptor along the length of the genome. These were unusually concentrated near a number of genes associated with susceptibility to autoimmune conditions such as multiple sclerosis (MS), systemic lupus erythematosus, Crohn’s disease and rheumatoid arthritis, and to cancers such as chronic lymphocytic leukaemia and colorectal cancer. The scientists also showed the vitamin’s significant effect on the activity of 229 genes including IRF8, previously associated with MS, and PTPN2, associated with Crohn’s disease as well as type 1 diabetes.

Apple genome sequencing will help grow better plants

Led by horticultural genomicist Dr. Amit Dhingra at Washington State University (WSU), a team of scientists from WSU and University of Washington (UW) in the United States sequenced and analysed a unique version of the genome of the golden delicious apple in which all duplicated chromosomes are genetically identical. This information was then used to validate the sequence of the more complicated heterozygous golden delicious apple.

Microbiologist Dr. Roger Bumgarner’s lab at UW provided the initial sequencing expertise to the project, which was later complemented and replaced by sequencing expertise in Dr. Dhingra’s genomics lab. WSU computational biologist Dr. Ananth Kalyanaraman contributed to the analysis by comparing the apple genome with that of pear, peach and grape to identify the differences and commonalities that exist between these fruit crops. Besides sequencing the apple genome, the team answered one old question. Scientists have for years argued vehemently about the ancestor of the modern domesticated apple. The question is now answered: Malus sieversii, a native of the mountains of southern Kazakhstan, is the apple’s wild ancestor. Now that that question is settled, scientists will begin using the apple genome to help breed apples with desirable new traits, such as disease resistance and more health-benefiting qualities.


Immune system protein could be a cancer research target

CD74 is a protein that is expressed in and on cells of the immune system, such as B lymphocytes and antigen presenting cells. This protein is known for its function in facilitating antigen presentation enabling the immune response. It also serves as a survival receptor on cells of the immune system, and that its stimulation by its natural ligand – migration inhibitory factor (MIF) – prevents apoptosis (self destruction) of these cells. CD74 is markedly expressed on numerous tumours – ematologic as well as epithelial – and can serve as a prognostic marker.

A team of scientists headed by Professor Idit Shachar from Weizmann Institute of Science, Israel, has demonstrated that CD74 is expressed on colon epithelial cells. CD74 expression on these cells was shown to increase colon epithelial cells survival upon stimulation by its natural ligand MIF. These findings were further supported by their demonstration in the mouse colorectal cancer cell line, CT-26. Stimulation of CD74 expressed on these cells led to Akt phophorylation and Bcl-2 expression resulting in elevation of cell survival. These findings could open a new target in the research of colorectal cancer.

Protein that shuttles RNA into mitochrondria

An essential cell protein plays a key role in shuttling RNA into the mitochondria, the “power plant” of the cell, according to scientists at Jonsson Comprehensive Cancer Centre, the Department of Chemistry & Biochemistry and the Department of Pathology & Laboratory Medicine of the University of California Los Angeles (UCLA), the United States. In the study, the UCLA scientists show a new role for a protein called polynucleotide phosphorylase (PNPASE) in regulating the import of RNA into mitochondria.

Reducing the expression of PNPASE decreased RNA import, which impaired the processing of mitochondrial genome-encoded RNAs. Reduced RNA processing inhibited the translation of proteins required to maintain the electron transport chain that handles oxygen to produce energy in the form of adenosine triphosphate (ATP), the energy currency of a cell. With reduced PNPASE, unprocessed mitochondrial RNAs accumulated, protein translation was inhibited and energy production was compromised, leading to stalled cell growth.

“The study yields new insight on how cells function at a very fundamental level. This information provides a potential new pathway to control mitochondrial energy production and possibly impact the growth of cells, including certain types of cancer cells,” said Dr. Michael Teitell, co-senior author of the study. The study could have implications for studying and treating certain cancers, which rely on cellular energy to grow and spread, as well as mitochondrial disorders such as neuromuscular diseases. Dr. Carla Koehler, co-senior author of the study said: “If we can understand how this pathway functions in healthy cells we could potentially uncover defects that help in transforming normal cells into cancer cells.”

Merlin protein controls liver stem cells, affects liver cancer

A protein known to be involved in a rare hereditary cancer syndrome may have a role in the regulation of liver stem cells and the development of liver cancer. A research team Massachusetts General Hospital (MGH), the United States, has found that the protein, called merlin and encoded by the neurofibromatosis type 2 (NF2) gene, controls the activity of adult stem cells that give rise to the two major types of liver cells.

The researchers found that infant mice lacking functioning NF2 tumour suppressor gene in their livers developed dramatic overgrowth of liver stem cells, to the point of crowding out hepatocytes. Mice that did not die from a lack of functioning liver cells soon developed the two major types of liver cancer, and the fact that stem cell overgrowth preceded tumour development strongly suggested that the undifferentiated progenitors were the source of the tumours. Blocking the expression of NF2 in the livers of adult mice had minimal effect on the animals unless a portion of the liver was surgically removed, setting off the regeneration process and leading to stem cell over-proliferation and tumour development. Dr. Andrea McClatchey, who led the research, explains that their findings provide new information about liver stem cells and how their proliferation is controlled; identifies a new animal model for liver cancer, the lack of which has seriously impeded understanding the disease; and suggests that liver tumours may originate from liver stem cells and that excess epidermal growth factor receptor (EGFR) signalling leads to liver tumour development. “We also showed that merlin’s role in cell-to-cell communication is essential for cells to stop growing when they fill the appropriate space. Since liver progenitors need to be poised to regenerate in case of injury, they may be particularly sensitive to the loss of merlin’s regulatory function,” Dr. McClatchey said.

A protein that can cause fragile bones

Too little of a protein called neogenin results in a smaller skeleton during development and sets the stage for a more fragile bone framework lifelong, researchers at Medical College of Georgia (MCG), the United States, report. A developing mouse with neogenin deficits has poorly defined digits and is generally smaller, including having small growth plates, an indicator of future development, said Dr. Wen-Cheng Xiong, developmental neurobiologist in the MCG Schools of Medicine and Graduate Studies and corresponding author of the study. Dr. Zheng Zhou, assistant research scientist, is first author.

Neogenin doesn’t make bone; rather, it forms a protein complex essential to turning on cartilage-producing genes. “Each cell type has a master gene. Neogenin is not that, it is more of a modulator,” Dr. Xiong said. If it is mutated, cartilage and bone formation is disrupted, though not halted. Neogenin could thus be a good therapeutic target for turning the tide on cartilage or bone loss that occurs in osteoarthritis. Neogenin, which helps direct neurons during brain development and aid in regulation of iron levels, is found throughout bone and cartilage and numerous other tissues. Dr. Xiong notes that neogenin’s pervasiveness reflects its many functions, depending on the stage of life and location. The researchers suspect the protein has multiple roles in adulthood as well, albeit slightly different ones. In adulthood, neogenin may be more of an overseer, keeping tabs on functions it influences, such as formation of bones. It resumes an instigator’s role when something goes amiss. These findings provide new insight into skeletal development, as they point towards a potential new direction for treating osteoarthritis.

Hybrid protein tools for gene cutting and editing

A team of researchers from Iowa State University, the United States, has developed a type of hybrid proteins that can make double-strand DNA breaks at specific sites in living cells, possibly leading to better gene replacement and gene editing therapies. The team led by Dr. Bing Yang, an assistant professor of genetics, development and cell biology, developed the hybrid protein by joining parts of two different bacterial proteins. One is called a TAL effector, which functions to find the specific site on the gene that needs to be cut, and the other is a nuclease enzyme that cuts the DNA strands.

Dr. Yang hopes the research will lead to the ability to modify genomes by cutting out defective or undesirable parts of DNA, or by replacing defective or undesirable gene segments with a functioning piece of replacement DNA – a process called homologous recombination. He says that his hybrid proteins can be constructed to locate specific segments of the DNA in any type of organism. “This breakthrough could eventually make it possible to efficiently modify plant, animal and even human genomes,” said Dr. Yang.

The proteins work by binding onto the specific segment of DNA that the researcher wants to change. They do this by finding the specific area to be cut in the DNA sequence. Once the protein binds onto the DNA at the correct spot, its other half cuts the double-stranded DNA. Bad or undesirable DNA can be resected (removed) and good or more desirable DNA can be introduced. When the DNA heals, the good DNA is included in the gene.

Engineered coral pigment helps scientists in protein study

A team of scientists has shown that a variant form of a fluorescent protein (FP) originally isolated from a reef coral has excellent properties as a marker protein for super-resolution microscopy in live cells. The scientists were from University of Southampton School of Ocean and Earth Science (SOES), the United Kingdom, and Karlsruhe Institute of Technology and University of Ulm in Germany. “Fluorescent pigments from corals and related animals have proved to be invaluable lead structures to produce advanced markers for biomedical research,” said Dr. Jörg Wiedenmann from SOES. “They enable a plethora of exciting experiments, including non-invasive study of dynamical processes within live cells.” Photoactivatable FPs (PA-FPs) can, as their name suggests, be switched on by light. When light of a particular wavelength is shone upon them they start to glow, emitting light of characteristic hue.

Dr. Wiedenmann and his collaborators previously described EosFP, a PA-FP from the reef-building coral Lobophyllia. Genetic engineering yielded the variant IrisFP with dual photoactivation capacity. In one mode, it is irreversibly ‘photo-converted’ from a green- to a red-emitting form under violet light. In a second mode, these two light-emitting forms can be switched on and off more or less at will using light of different wavelengths (‘photo-switching’). For use in cell biology experiments, PA-FPs are genetically fused to proteins of interest, and expressed in live cells. Small regions of the cell are then illuminated with laser light of specific wavelength, causing the marker proteins to emit light at another wavelength. This allows dynamical cell processes to be visualised and studied under the microscope. In the native state, four molecules of IrisFP join together to form a tetramer, creating problems for fusion-protein applications. To get round this, the scientists modified the protein by introducing four mutations, which reduces the tendency of individual IrisFP molecules (monomeric, mIrisFP) to form tetramers. This mIrisFP maintains dual photoactivation capacity and possesses excellent properties as a genetically encoded fluorescent marker protein, explained Dr. Wiedenmann.


Brain cells on silicon chip

Medical scientists at University of Calgary, Canada, who proved it is possible to cultivate a network of brain cells that reconnect on a silicon chip, have been involved in the development of new technology that monitors brain cell activity at a resolution never achieved before. The simpler-to-use silicon chips, developed jointly with the National Research Council Canada (NRC), will help future understanding of how brain cells work under normal conditions and permit drug discoveries for a variety of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

“This technical breakthrough means we can track subtle changes in brain activity at the level of ion channels and synaptic potentials, which are also the most suitable target sites for drug development in neurodegenerative diseases and neuropsychological disorders,” says Prof. Naweed Syed, who heads the Department of Cell Biology & Anatomy, and a member of the Hotchkiss Brain Institute. The new “neurochips” are automated. Previously it took years of training to learn how to record ion channel activity from brain cells, and it was only possible to monitor one or two cells simultaneously. Now, larger networks of cells can be put on a chip and observed in minute detail, allowing the analysis of several brain cells networking and performing automatic, large-scale drug screening for various brain dysfunctions.

New cellular ‘armour’ prevents infection by AIDS virus

In Spain, research led by Dr. Félix Goñi, Director of the Biophysics Unit at Consejo Superior de Investigaciones Científicas-Universidad del País Vasco (CSIC-UPV) Joint Centre, has led to the development of a novel method of attack against the human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS). The method involves creating a prevention system – an ‘armour’ in the cells likely to be infected and thus impede the virus from accessing them and compromising the immune system. Except one, practically all current treatments for AIDS virus are based on halting the progress of the virus once it is inside the host cell.

The study – which also had the participation of a team from the CSIC Centro Nacional de Biotecnología (CNB) and another from the CSIC Instituto de Quimic Avanzada de Cataluña (IQAC) – lays down the bases of possible future pharmaceutical drugs that will enable combating HIV at its initial phase. It is based on the regulation of the fluidity of the cell membranes and seeks to avoid the phenomenon known as the fusion of membranes, a consequence of contact between the cell membranes and the membrane of the virus itself. What the researchers are seeking with this study is to strengthen the cell membrane structure, making it more rigid, in order to avoid fusion of membranes and, thus, the inoculation of the cell by HIV.

The research started three years ago and has employed various techniques in the field of chemistry and molecular biology. Dr. Gemma Fabriàs at IQAC synthesised the GT11 molecule, Dr. Santos Mañes from CNB studied the viral infection of the cells, and the CSIC-UPV Joint Centre carried out work at the molecular level to demonstrate the changes in the rigidity of the membranes when the GT11 molecule is incorporated into them.

Thymus cells transform into skin cells

Researchers have been able to transform cells taken from the thymus into skin cells – a discovery that may have important ramifications for the field of organ regeneration. In collaboration with University of Edinburgh, the United Kingdom, a Swiss research team isolated thymic epithelial cells (TECs) from the thymus of a rat and integrated them into the rat’s skin cells with surprising results. The findings show that these stem cells change their genetic make-up according to their environment to contribute to the long-term functioning of the skin, even producing hair for up to a year after implantation. TECs switched over from what they were originally intended for – teach T-cells to recognize and destroy bacteria and cancer cells – and took up a novel role in accordance with their new environment.

“These cells really change track, expressing different genes and becoming more important,” explains Prof. Yann Barrandon, who heads Stem Cell Dynamics Laboratory, a chair shared by the Ecole Polytechnique Fédérale de Lausanne (EPFL), the University of Lausanne and its teaching hospital Centre hospitalier universitaire vaudois.

The experiment’s results show that TECs have the ability to express genetic markers, unlike its original make-up, when placed in different micro-environments. Until now, experiments using hair follicle stem cells to maintain hair and skin growth have met with limited results. TECs have proven effective for up to a year after implantation, a major improvement over the three-week performance of bona fide hair follicle stem cells. These findings can not only create new opportunities in the field of organ transplantation and regeneration, but also call into question standard biological models by showing that it is possible to create tissues from cells with different embryonic origins.

Nanotech enables doctor’s camera to see cancer cells

Researchers in the United States have added nanotechnology to an off-the-shelf digital camera to help doctors distinguish healthy cells from cancerous cells in the human body. Rice University scientists said that doctors can use the souped-up camera to see cancerous cells on the camera’s LCD monitor. Targeted nanoparticles deliver fluorescent dyes to help doctors easily and quickly distinguish healthy from dangerous cells.

When the nanoparticles deliver dye to the cell, a small bundle of fibre-optic cables attached to a US$400 Olympus E-330 digital camera capture images. The dyes cause the cell nuclei to glow brightly when lighted with the tip of the fibre-optic bundle. Dr. Rebecca Richards-Kortum, a Rice University professor and the study’s lead author, noted that because the nuclei of cancerous and pre-cancerous cells are notably distorted from those of healthy cells, abnormal cells are easily identifiable. The scientists tested three different types of cells: cancer cell cultures that were grown in a lab; tissue samples from newly resected tumours; and healthy tissue seen in the mouths of patients.

Key step in body’s ability to make red blood cells found

At Southwestern Medical School of University of Texas, the United States, researchers found that a tiny RNA fragment prompts stem cells to mature into red blood cells. The researchers also created an artificial RNA inhibitor to block this process. Such interventions, if fruitful in humans, might be useful against some cancers and other diseases, such as polycythemia vera, in which the body produces a life-threatening excess of blood cells. Conversely, a drug that boosts red blood cell production might be useful against anaemia, blood loss or altitude sickness. “The important finding is that this microRNA, miR-451, is a powerful natural regulator of red blood cell production,” said Dr. Eric Olson, senior author of the study and Chairman of Molecular Biology. “We also showed that a man-made miR-451 inhibitor can reduce miR-451 levels in a mouse and block blood-cell production. We hope that this inhibitor and similarly functioning molecules might lead to new drugs against the fatal disease polycythemia vera, which currently has no therapies,” said Dr. Olson.

Novel bee venom derivative to target cancer cells

Melittin, a toxic protein in bee venom, when altered, significantly improves the effectiveness liposome-encapsulated drugs or dyes, such as those used to treat or diagnose cancer. “This type of transporter agent may help in the design and use of more personalized treatment regimens that can be selectively targeted to tumours and other diseases,” said Dr. Samuel A. Wickline, a scientist involved in the work from the Consortium for Translational Research in Advanced Imaging and Nanomedicine (C-TRAIN) at the Washington University School of Medicine in St. Louis, the United States.

To make this discovery, Dr. Wickline and colleagues designed and tested various versions of the melittin protein, to derive a stable compound that could be inserted into liposomal nanoparticles and into living cells without changing or harming them. The scientists then tested the ability of this transporter agent to attach to different therapeutic compounds and enhance drug therapy without causing harmful side effects. Research results also suggest that the base compound used to create the transporter agent may improve tumour therapy.

Biosynthetic corneas restore vision in humans

A new study by scientists in Canada and Sweden has shown that biosynthetic corneas can help regenerate and repair damaged eye tissue and improve vision in humans. “With further research, this approach could help restore sight to millions of people who are waiting for a donated human cornea for transplantation,” said senior author of the study Dr. May Griffith of the Ottawa Hospital Research Institute, the University of Ottawa, Canada, and Linköping University, Sweden.

More than a decade ago, Dr. Griffith and her colleagues began developing biosynthetic corneas in Canada, using collagen produced in the laboratory and moulded into the shape of a human cornea. After extensive laboratory testing of the synthetic cornea, Dr. Griffith began collaborating with an eye surgeon, Dr. Per Fagerholm from Linköping University, to provide the first-in-human experience with biosynthetic cornea implantation. Together, they started a clinical trial in 10 Swedish patients with advanced keratoconus or central corneal scarring. Each patient underwent surgery on one eye to remove damaged corneal tissue and replace it with synthetic cornea, made from cross-linked recombinant human collagen.

Over two years of follow-up study, the researchers observed that the cells and nerves from the patients’ own corneas had grown into the implant, resulting in a “regenerated” cornea resembling normal, healthy tissue. Patients did not experience any rejection reaction or require any long-term immune suppression, which are serious issues associated with the use of human donor tissue. The biosynthetic corneas also became sensitive to touch and began producing normal tears to keep the eye oxygenated. Vision improved in six of the ten patients, and after contact lens fitting, vision was comparable to conventional corneal transplantation with human donor tissue. “We are very encouraged by these results and by the great potential of biosynthetic corneas,” said Dr. Fagerholm.


Wild canola plants acquire modified genes

In the United States, scientists at the University of Arkansas, North Dakota State University, California State University-Fresno and the Environmental Protection Agency (EPA) have found populations of wild plants with genes from genetically modified (GM) canola. Globally, canola can interbreed with 40 different weed species, and 25 per cent of those weeds can be found in the United States. These findings raise questions about the regulation of herbicide-resistant weeds and how these plants might compete with others in the wild.

“We really don’t know what the consequences of the gene escape,” said Ms. Meredith Schafer, a graduate student. The research originated when Ms. Schafer and Dr. Cynthia Sagers, biological sciences professor at the University of Arkansas, spotted some weeds with yellow flowers in a ditch in Langdon, North Dakota. As part of another research project, they had some portable strips that test for GM proteins in canola that impart herbicide resistance to crop plants. The strips tested positive for a modified protein that confers herbicide resistance on canola, confirming that the weeds contained transgenic genes.

The researchers then surveyed canola plants in a 50 metre transect and tested plant samples. They repeated the exercise at several locations in North Dakota, travelling nearly 5,000 km. They found wild canola in about 46 per cent of the sites along the highway. Approximately, 83 per cent of the weedy canola they tested contained transgenic material. Importantly, some of the plants contained resistance to two different herbicides, a combination of transgenic traits. “That is not commercially available. That has to be happening in the wild,” Ms. Schafer said. That led the researchers to believe that the wild populations had become established populations, although the plants were not expected to be able to compete in the wild. A wider spread of these plants could create problems, as eradicating the weeds would not be possible with available herbicides.

Production of biofuels from straw

Süd-Chemie AG, Germany, is to build the country’s largest plant to date for the production of climate-friendly, second-generation bioethanol (cellulose ethanol), based on biotechnological processes. As from the end of 2011, this large-scale demonstration plant, located in Straubing, will produce up to 2,000 tonnes per year of bioethanol fuel from agricultural waste, such as cereal straw, using Süd-Chemie’s sunliquid® process.

The sunliquid process, which Süd-Chemie has been testing in a pilot plant since the beginning of 2009, is an innovative method of producing second-generation bioethanol in a cost-effective and energy-efficient manner. Cellulose-based plant residue, such as wheat straw or maize straw, sugar cane bagasse or so-called energy crops, are initially converted into sugar constituents with the aid of enzymes. Bioethanol is then extracted from these constituents and used as fuel.

In the case of Süd-Chemie’s process, not only the cellulose contained in plants, but also hemi-cellulose can be converted into ethanol, making it possible to increase ethanol production by up to 50 per cent compared with conventional technology. Furthermore, the enzymes needed to convert the cellulose can be optimized, depending on the original raw materials used and produced directly on the spot in each production plant. This guarantees an optimal enzyme supply, being both highly efficient and cost-effective.

Boosting fungal disease resistance in legumes

In Australia, a study funded by Grains Research and Development Corporation (GRDC) has identified genetic material that could be employed to reduce the impact of some fungal diseases on legumes and other crops. The ‘Genetic dissection of fungal disease resistance in legumes’ project in Western Australia (WA) has generated genetic material with resistance to the pathogen Rhizoctonia solani, which causes root rot in all legumes as well as in cereals and canola. It has also identified genetic material resistant to the exotic fungal disease Fusarium oxysporum, which causes wilt diseases.

The project is being led by Dr. Karam Singh, programme leader at the Commonwealth Scientific and Industrial Research Organization (CSIRO) Plant Industry in WA and Winthrop Professor at the University of Western Australia. The research also involves the Australian Research Centre for Necrotrophic Fungal Pathogens in WA.

Controlling root rot and wilt is difficult because of limited rotational controls and a lack of resistant cultivars, Prof. Singh said. “The project screened a number of different pathogens to try to find genetic variation in the susceptibility of germplasm to R. solani and F. oxysporum.” The researchers found strong natural resistance in Medicago germplasm to F. oxysporum and mapped the genetic material underlying that resistance. “We have been unable to find strong resistance to R. solani in Medicago but have used a novel approach to develop effective resistance to the pathogen.” Prof. Singh explained. The genetic material identified with resistance to F. oxysporum and R. solani can potentially be deployed in breeding programmes to help develop new legume varieties with disease resistance.

Gene discovery could help to boost crop yields

A recent discovery by scientists at the University of York’s Centre for Novel Agricultural Products (CNAP), United Kingdom, of a vital feature of a plant’s temperature sensing and growth mechanism could help increase yields from crops. The researchers found a gene, called SPT (Suppressor of Ty), that plays a significant role in the growth rate of the model plant Arabidopsis thaliana. Plants that are without the SPT gene grow at a faster rate at lower temperatures, but have the same tolerance to freezing as plants with the gene.

The work also shows that daytime temperatures have a particular influence on plant growth and that the SPT gene allows plants to measure temperature in the morning. Dr. Steve Penfield, who led the research team said: “There is potential for this discovery to be used to increase crop yields by extending the growing season particularly in spring and autumn.” The study also involved Institute of Molecular Plant Sciences in the School of Biological Sciences at University of Edinburgh, the United Kingdom.

Fungi’s genetic sabotage in wheat

Using molecular techniques, researchers of the Agricultural Research Service (ARS), the United States Department of Agriculture (USDA), and collaborating agencies have shown how the subversion of a single gene, Tsn1, in wheat by two fungi triggers a kind of cellular suicide in the grain crop’s leaves. The team has also developed DNA molecular markers that can be used to rapidly screen commercial cultivars for Tsn1, so that it can be eliminated by selective breeding. This will, in turn, deprive the fungi of their primary means of killing off leaf tissue to feed and grow, explains Dr. Justin Faris, a plant geneticist with the ARS Cereal Crops Research Unit.

The fungi – Pyrenophora triticirepentis (tan spot) and Stagonospora nodorum (leaf blotch) – are often partners in crime, occurring in the same crop fields and producing the same toxin, ToxA, to induce a Tsn1-controlled response in wheat called programmed cell death (PCD). Normally, PCD protects plants by confining invading pathogens in dead cells. However, the strategy doesn’t work against the ToxA fungi because they are “necrotrophs” that feed on dead tissue.

To better understand this genetic trickery, Dr. Faris led a team of scientists from seven different research organizations in isolating, sequencing and cloning the DNA sequence for Tsn1 from cultivated wheat and its wild relatives. Tsn1 is controlled by wheat’s circadian clock, and only initiates PCD in response to ToxA during daylight hours. At night, Tsn1 shuts down and “ignores” ToxA, suggesting the toxin may indirectly interfere with the plant’s photosynthesis.

Quest for aphid-resistant soybean varieties

Two lines of pest-resistant soybean developed by a scientist at Michigan State University, the United States, promise healthier harvests for growers. “Sparta – the Soybean Aphid Shield” is the new trade name for genetics developed by Dr. Dechun Wang, an associate professor of crop and soil science who tested some 2,000 strains of soybeans against aphids to isolate four with different resistant genes. From those he developed germplasm to breed into varieties that are suited to Michigan’s shorter growing season. “The final goal,” Dr. Wang said, “would be to have one variety that has all those resistant genes,” maximizing protection against different biotypes of aphids. Soybean aphids suck plant sap and secrete sticky honeydew that promotes sooty black mould, and when they sprout wings can widely transmit plant viruses. “It takes aphids just five days to produce more babies, and aphids are born pregnant, so the regeneration cycle is incredibly fast,” Dr. Wang said. One application of insecticide might add 10 per cent to the cost of production and kill beneficial insects as well.

Sweet pepper genes arm banana against wilt disease

In a major breakthrough, crop scientists have successfully transferred genes from green pepper to bananas, enabling the crop to resist the Banana Xanthomonas Wilt (BXW), a devastating disease that affects almost all types of banana. Presently, there are no commercial chemicals, biocontrol agents or resistant varieties that could control BXW. The transformed banana, infused with plant ferredoxin-like amphipathic protein (Pflp) or hypersensitive response-assisting protein (Hrap) from green pepper, have exhibited strong resistance to BXW in the laboratory and greenhouses.

Scientists from the International Institute of Tropical Agriculture (IITA) and the National Agricultural Research Organization (NARO) of Uganda, in partnership with the African Agricultural Technology Foundation (AATF), would soon be evaluating these resistant lines under confined field trials after the Ugandan National Biosafety Committee’s approval.

“The Hrap and Pflp genes work by rapidly killing the cells that come into contact with the disease-spreading bacteria, essentially blocking it from spreading any further,” said Dr. Leena Tripathi, a biotechnologist with IITA and the lead author of the paper. “Furthermore, the mechanism known as hypersensitivity response also activates the defence of adjacent and even distant uninfected plants leading to a systemic acquired resistance,” she added. Hrap and Pflp are novel plant proteins that give crops enhanced resistance against deadly pathogens.


Biotechnology: Cracking New Pastures

The book Biotechnology: Cracking New Pastures discusses selected topics to provide the reader a sound knowledge of selected areas in different guises, ranging from lectins, RNAi, bacterial biosorption of heavy metals, increasing yield potential of grain legumes and endophytic fungi to prions and advances in DNA transfer. Each topic is written by an expert and offers up-to-date information. Profusely used images and extensive literature citations form the strength of this book. Several authors and co-authors have worked on this project. The book is the definitive source for those who are keen to remain updated on the recent advances in biotechnology.

Contact: MD Publications Pvt. Ltd., MD House, 11, Darya Ganj, New Delhi 110002, India. Tel: 91 (11) 4535 5555; Fax: 91 (11) 2327 5542; E-mail:; Website:

Plant Biotechnology for Sustainable Production of Energy and Co-products

This volume discusses uses of plant biomass as well as ways to improve the productivity and composition of plant species – including trees, annual and perennial grasses, oil-producing plants and algae – that have the potential to produce substrates such as sugar, starch, oil and cell walls, as well as energy and co-product substrates. The problems of invasiveness and gene dispersal are discussed, as are ways to mitigate these. The topics covered include models for integrated biorefineries to produce many co-product chemicals, the use of corn stover to power ethanol plants, life cycle analysis of biofuels, and criteria for biomass sustainability and certification.

Contact: Springer GmbH, Haberstrasse 7, 69126, Heidelberg, Germany. Tel: +49 (6221) 345 4301; Fax: + 49 (6221) 345 4229; E-mail:


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