VATIS Update Biotechnology . Apr-Jun 2012

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Biotechnology Apr-Jun 2012

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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Immunization takes a new turn in India

In a move set to change the history of immunization in the country, the Government of India has started administering pentavalent vaccine in place of the existing diphtheria- pertussis-tetanus (DPT) vaccine in a phased manner in the southern states of Kerala and in Tamil Nadu. Apart from those covered by DPT vaccine, the new vaccine offers immunity against hepatitis B (HepB) and Haemophilus influenza Type B (HiB).

Following a recommendation by the World Health Organization (WHO) that pentavalent vaccine be administered to every child in the world, the Government of India asked the National Technical Advisory Group on Immunization (NTAGI) to study the need for HepB and HiB vaccines in the Indian population. An NTAGI report submitted four years back recommended the introduction of HiB vaccine in all states as early as feasible. NTAGI quoted studies carried out in India that reported fatality rates of HiB meningitis to be 20-29 per cent, and fatality rate of all invasive Hib diseases (including meningitis) to be 16 per cent. NTAGI recommended the use of HiB vaccine, as it has the potential to prevent over 70,000 deaths of children below five years of age.

Cost remains a crucial factor that cannot be ignored while introducing an immunization drive in a large country like India. Currently, GAVI Alliance, based in Switzerand, has agreed to supply pentavalent vaccines free of cost to India for a period of three years. The vaccine that GAVI supplies is Pentavac, manufactured by Serum Institute of India (SII). Ms. Aurélia Nguyen, Director of Policy, GAVI, says that GAVI will be funding the vaccine in Kerala and Tamil Nadu throughout 2012, which will be more than 6.2 million doses. GAVI is working with the Indian government to explore how it can extend its support and set a work programme customized to India’s priorities.

United Kingdom endows £250 million to life sciences

United Kingdom’s Minister for Universities and Science, Mr. David Willetts, has announced that £250 million has been allocated for the first phase of five-year strategic investment programmes. This allocation covers 26 strategic science programmes and 14 key national research capabilities, to be delivered by eight of the nation’s world-leading bioscience research institutes and their university partners. The process will be led by the Biotechnology and Biological Sciences Research Council (BBSRC). The plan is thought to help the United Kingdom meet challenges such as sustainably feeding the growing world population, finding alternatives to dwindling fossil fuels and supporting an ageing society to remain healthy for longer.

The Minister made the announcement in a speech during a visit at the Babraham Research Campus. The campus, a BBSRC National Research and Innovation Campus, is one of the privileged institutes and will receive £37 million. Others are the Institute of Biological, Environmental and Rural Sciences, Aberystwyth University (£13 million), the Genome Analysis Centre in Norwich (£19 million), the Roslin Institute at the University of Edinburgh (£23 million), the Institute for Animal Health in Pirbright (£38 million), the Institute of Food Research in Norwich (£29 million), the John Innes Centre in Norwich (£42 million) and the Rothamsted Research in Harpenden (£41 million).

Experts push for sorghum in biofuel crop mix

Sweet and biomass sorghum would meet the need for next-generation biofuels to be environmentally sustainable, easy to adopt by producers and take advantage of existing agricultural infrastructure, say a group of researchers led by scientists from Purdue University, the United States. “As we move to different fuels beyond ethanol, the ethanol plants of today are equipped to take advantage of new bioenergy crops,” observed Dr. Nick Carpita, a professor of botany and plant pathology. The scientists argue that no single plant is a silver-bullet answer to biofuels; however, sorghum should be a larger part of the conversation than it is today.

Some types of sorghum would require fewer inputs and could be grown on marginal lands, noted Dr. Cliff Weil, a professor of agro-nomy. “In the near future, we need a feedstock that is not corn,” he said. “Sweet and biomass sorghum meet all the criteria. They use less nitrogen, grow well and grow where other things don’t grow.” The ability to minimize inputs such as nitrogen could be a key to sorghum’s benefits as a bioenergy crop. Dr. Carpita said corn, which has been bred to produce a maximum amount of seed, requires a lot of nitrogen. But sorghum could be genetically developed in a way that maximizes cellulose, minimizes seeds and, therefore, minimizes inputs.

Farmers may also be more willing to grow sorghum because it is an annual, unlike perennials such as switchgrass or Miscanthus, which would take up a field for a decade or longer. Sorghum would fit in a normal crop rotation with food crops rather than tying up valuable cropland. Dr. Farzad Taheripour, a research assistant professor of agricultural economics, said: “Given that sorghum can be produced on low-quality, marginal lands in dry areas, producing sorghum for biofuel will significantly improve the economy of rural areas that rely on low-productivity agriculture.”

Indo-US deals in vaccine research

Both India and the United States are making collaborative efforts in life sciences, and the vaccine sector has particularly benefited from these joint R&D projects in the past five years. India has received continued help from the United States in various domains of science and technology, and there are several advantages that India offers to the United States. The factors in favour of India include its large pool of skilled and cost-competitive workforce, advanced chemical synthesis technologies, manufacturing practices that conform to the United States and European Union norms, and global recognition as a producer of low-cost, high-quality bulk drugs and formulations.

One collaboration is between Indian vaccine major Serum Institute of India (SII) and the United States vaccine giant Merck to develop and commercialize pneumococcal conjugate vaccine (PCV) for use in the emerging and developing world. Besides SII, Biocon, Shantha Biotechnics and Bharat Biotech too have forged alliances with United States companies or organizations in areas such as biopharma and vaccines. Bharat Biotech has entered into collaboration for the development of its rotavirus vaccine, Rotavac, with several United States public and private organizations that include Centres for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), and Stanford University. Similarly, Shantha Biotechnics has had a collaborative deal with NIH and the international agency Programme for Appropriate Technologies in Health (PATH) for the development of a rotavirus vaccine. The technology in this case has been licensed from the NIH.

Animal vaccine company Indian Immunologicals (IIL) has several collaborations with institutes in the United States, such as Veterinary Technologies Corp. (for brucellosis vaccine) Harvard Medical School (for polysaccharide vaccines). It also has a partnership with CDC for hepatitis A and rabies vaccines. In 2009, Syngene International, a subsidiary of Indian biotechnology major Biocon, and Bristol-Myers Squibb (BMS) opened a dedicated research facility for the latter in Bangalore, India. The 18,580 m2 facility is dedicated to augmenting BMS’ work in discovery and early drug development. Panacea Biotec has an in-licensing arrangement with NIH for use of a peptide-based product for generation of hair follicles and hair growth.

Philanthropic organizations have also been instrumental in forging joint research collabourative deals between the two countries in the recent years, especially in the area of vaccines. In March 2011, the Bill and Melinda Gates Foundation (BMGF) announced grants to fund late-stage clinical trials to SII and Bharat Biotech for pneumonia and rotavirus vaccines, respectively. BMGF is expected to grant about US$30 million for late-stage clinical trials of rotavirus vaccines.

Russia backs clones of Western biotech programmes

Investors from Russia is receiving financial support from the Russian government for licensing drugs from Western companies and developing them for the market in Russia, putting smiles on the faces of the United States and European biotech companies in the process. For instance, Moscow-based Maxwell Biotech Venture Fund, which is 50 per cent backed by the Russian government, formed Hepatera last year to develop treatments for liver diseases, with the start-up’s lead drug for hepatitis B licensed from German biotech MYR. With backing from Moscow, Hepatera will now develop MYR’s hepatitis B drug for the Russian market. RusNano, another government-backed venture fund, has joined forces with venture firm Domain Associates of the United States with the stated goal of funnelling science from abroad into Russia for development and marketing in the country.

Maxwell Biotech Venture Fund, has opened an office in Boston, the United States, with a mandate to score good returns on investments as well as to sow the seeds of the biotech industry in Russia. For the Hepatera-MYR deal, Maxwell joined hands with German venture outfit High Tech Gründerfonds, which is also backing MYR. The Russian government-supported funds have been very active in life sciences investing lately, a positive development for early-stage drug developers across the world.


Novozymes partners with Sea6 Energy for biofuels production

Global biotech major Novozymes, Denmark, has partnered with biotech start-up Sea6 Energy, India, for exploratory research and to develop jointly a process for the production of biofuels from seaweed. The research alliance is expected to use enzymes to convert carbohydrates contained in seaweed to sugar, which can then be fermented to produce ethanol for fuel, fine chemicals, proteins for food, and fertilizers for plants.

According to Mr. Shrikumar Suryanarayan, Chairman, Sea6 Energy, the company has developed ocean-farming structures that can be used to establish large-scale seaweed farms in offshore locations. “In addition, Sea6 Energy is also pioneering approaches to fermenting the sugars derived from seaweed to produce fuel in a manner that requires minimal use of fresh water resources,” he said. Novozymes will research, develop and manufacture enzymes for the conversion process, while Sea6 Energy will contribute its offshore seaweed cultivation technology. “Seaweed is a natural complement to our efforts to convert other types of biomass to fuel ethanol,” said Mr. Per Falholt, Executive Vice-President and Chief Scientific Officer of the company.

Sinovac makes progress in EV71 clinical trial

Sinovac Biotech, a leading provider of biopharmaceutical products in China, is conducting double-blind, randomized, placebo-controlled Phase III trial for its proprietary inactivated Enterovirus 71 (EV71) vaccine against hand, foot and mouth disease (HFMD) at three sites across China’s Jiangsu province. This study aims to demonstrate the efficacy of the vaccine in preventing diseases caused by EV71 in infants 6 to 35 months old. About 10,000 healthy infants completed the vaccination schedule in the first quarter of 2012, prior to the epidemic season for HFMD in China. The disease surveillance period began 28 days after completion of the two-dose regimen.

A three-arm active surveillance system – comprising village health clinics, township hospitals as well as county Centres for Disease Control and Prevention – has been established at each clinical site and is in charge of epidemic surveillance, case diagnosis, epidemiological survey and sample collection. A number of patients with HFMD symptoms have been identified as EV71-positive. All professionals in the surveillance system are actively monitoring the epidemic situation to try to achieve the clinical target early. Dr. Weidong Yin, Chairman and CEO of Sinovac Biotech, described the current epidemic situation as “one of the most serious in the past five years, with a nearly 110 per cent increase in reported cases between January 2012 and May 2012, and with almost twice the number of fatalities”.

Merck, Flagship join forces on fostering biotech start-ups

In the United States, after raising US$270 million for its new biotech fund, Flagship Ventures is teaming up with a pair of key Merck units – Merck Research Laboratories and its newly formed Merck Research Ventures Fund – to collaborate on fostering a string of innovative new drug developers. In what is being billed as an early-stage investment backed by Big Pharma expertise on development and commercialization, Flagship is looking at this as a new twist on a major novel theme in start-ups. In this case, Merck gets a seat at the table of new biotech companies that promise to launch important new treatments. With its own incubator and a host of top researchers with an entrepreneurial bent, Flagship, gets a big player to step up and lend a hand of essential support.

Ranbaxy launches its antimalarial drug

Ranabaxy Laboratories, India, has launched the country’s first indigenously developed medicine to cure malaria. The new drug, called Syrniam, treats Plasmodium falciparum malaria in adults. The three-tablet course has a cure rate of 95 per cent, and needs no dietary restrictions of fatty foods or milk, unlike existing anti-malarial therapies. The drug launch ended a 15-year drug discovery wait for Indian drug manufacturers who had been focusing on developing generic drugs.

“Since Synriam has a synthetic source, production can be scaled up whenever required and a consistent supply can be maintained at a low cost. We hope that this could potentially replace artemisinin-based combination therapies, which have their limitations in terms of production and supply as the molecules are derived from plants,” stated India’s Health Minister, Mr. Ghulam Nabi Azad, at the launch. The National Institute of Malaria Research of the Indian Council of Medical Research (ICMR), planned and conducted the clinical studies in partnerships with medical colleges and hospitals in Jharkhand, Karnataka and Odisha.

BioValence targets next-gen antiviral technology

Malaysia-based biopharma start-up company BioValence is developing next-generation antiviral technologies and multifunctional drugs that target viruses at multiple points of their life cycle in human, livestock, aquaculture and companion animals. BioValence recently collaborated with Defensia, also from Malaysia, to scale-up its RetroMAD1 technology to the next level of commercialization. RetroMAD1 is a chimeric anti-microbial peptide (ChAMP) drug expressed using Escherichia coli as recombinant protein cell factories. RetroMAD1 is mastered with protein refolding technology that allows simple up-scale production. It has proven in vitro efficacy against oral herpes, genital herpes and dengue fever. BioValence has signed up with a company from Philippines to test RetroMAD1 on porcine viruses.

BioValence is completing a recombinant protein plant that will supply shrimp hatcheries worldwide with a broad-spectrum therapeutic to ensure that viruses occurring at the hatchery-level are not transmitted to grow-out farms, said Mr. Ung Eng Huan, Chief Technology Officer, BioValence. The company is one of the few labs in the world that are working on oral delivery broad-spectrum antiviral. It is also conducting multi-centre trials in cats for Feline Immunodeficiency Virus and Feline Leukaemia Virus, and in dogs for Canine Parvo Virus.

Life Technologies, OpGen collaborate for genome mapping

In the United States, Life Technologies Corporation and OpGen Inc., a commercial stage whole genome analysis company, have signed a collaboration agreement to develop systems, technologies and applications intended to improve the management and surveillance of microbial outbreaks in the public health and infectious disease sectors. “OpGen’s Whole Genome Mapping technologies in conjunction with the Ion Torrent system will provide a valuable new approach that will provide public health and clinical laboratories access to cutting-edge technologies for microbial analysis and outbreak management,” said OpGen’s Chief Executive officer Mr. Douglas White.

OpGen’s Whole Genome Mapping technology provides a rapid, comprehensive structural analysis of microbial genomes that, when combined with sequencing data, more accurately detects important novel genetic elements associated with toxicity, virulence and drug resistance. As part of the collaboration, Life Technologies will also join the public health consortium recently established by OpGen to evaluate Whole Genome Mapping and sequencing for confirmation and management of disease outbreaks.

AstraZeneca partners up with Amgen antibodies

AstraZeneca plc., headquartered in the United Kingdom, and Amgen Inc., based in the United States, have struck a collaboration deal designed to strengthen each company where it needs help the most. AstraZeneca partnered on a slate of five early- to middle-stage anti-inflammation antibody candidates, adding to the potential of a weak pipeline. Amgen picked up a US $50 million upfront payment and a deep-pocket partner able to cover some of the R&D expenses.

In the deal, the two big developers agreed to set up joint governance groups for Amgen’s five human monoclonal antibodies (AMG 139, 157, 181, 557 and 827). AstraZeneca will finance two-thirds of the R&D expenses for 2012-2014, with an even split envisioned from 2015 onwards. It will take the lead on 139, 157 and 181, while Amgen will be primarily responsible for 557 and 827. The companies will split the profits for any treatments that move on to an approval.

CSIRO gets patents on RNAi gene silencing technology

The Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australia, has secured foundational patents in the United States and Europe for short hairpin RNAi (shRNA) gene silencing technology. shRNA technology, widely used as a research tool to test the function of genes, is being developed for a range of targeted therapies in humans and animals. The newly granted patents substantially strengthen CSIRO’s already extensive RNAi portfolio of more than 60 patents, stemming from the pioneering work of CSIRO Plant Industry scientists who developed hairpin RNA in 1997. The technology, first used in plants, has since been developed for use in animals, particularly in mammals.
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Gene therapy could boost brain repair in nerve diseases

Demyelinating diseases, like multiple sclerosis (MS), damage myelin, a protective covering of nerve cells (neurons), leaving neurons without their protective sheaths. The affected neurons can no longer communicate correctly and are prone to damage. At the California Institute of Technology (Caltech), the United States, researchers now believe that they have found a way to help the brain replace damaged myelin and oligodendrocytes, the specialized cells that make myelin. “We have developed a gene therapy to stimulate production of new oligodendrocytes from stem and progenitor cells – both of which can become more specialized cell types – that are resident in the adult central nervous system,” claims Dr. Benjamin Deverman, lead author of the study. “In other words, we are using the brain’s own progenitor cells as a way to boost repair.”

The therapy uses leukemia inhibitory factor (LIF), a natural protein known to promote the self-renewal of neural stem cells and to reduce immune-cell attacks to myelin in other MS mouse models. According to the researchers, LIF enables remyelination by stimulating oligodendrocyte progenitor cells to proliferate and make adequate oli-godendrocytes, something that the brain fails to, after demyelination. Once the researchers stimulated the proliferation of the progenitor cells, it appeared that the progenitors knew just what was needed. And they found that LIF elicited such a strong response that the treated brain’s levels of myelin-producing oligodendrocytes were restored to those found in healthy populations. The researchers note, too, that by placing LIF directly in the brain, one avoids potential side effects of the treatment that may arise when the therapy is infused into the bloodstream. This new application of LIF is an avenue of therapy not previously explored in human MS patients, explains Dr. Deverman. He points out that LIF’s benefits might also be beneficial for patients with spinal-cord injury, since the demyelination of spared neurons may contribute to disability in that disorder.

DNA sequencing helps defend body against cancer cells

DNA sequences from tumour cells can be used to direct the immune system to attack cancer, according to scientists at Washington University School of Medicine, the United States. The immune system relies on an intricate network of alarm bells, targets and safety brakes to determine what and when to attack. The new research results suggest that scientists may now be able to combine DNA sequencing data with their knowledge of the triggers and targets that set off immune alarms to more precisely develop vaccines and other immunotherapies for cancer. Dr. Robert Schreiber, a senior author of the study and the Alumni Professor of pathology and immunology, “To our knowledge, this is one of the first studies to show that the faster methods provided by DNA sequencing can help. That opens up all kinds of exciting possibilities.”

The immune system can recognize cancer as a threat – either on its own or with the help of vaccines or other immunotherapeutic treatments – and consequently, launch an attack on the cancer cells. Dr. Schreiber and his colleagues have shown that the interactions between cancer cells and the immune system are quite complex. Their theory, called cancer immunoediting, suggests that the immune system very easily recognizes some of the mutations in tumour cells as a threat, and attacks until they are destroyed. At that point, the cancer may be eliminated. But it is also possible that the cancer gets “edited” by the immune system, resulting in the removal of all the cells containing the critical, easily recognized mutations. The remaining tumour cells can continue to grow or enter into a period of dormancy where they are not destroyed but only held in check by the immune system.

Dr. Schreiber and his team induced tumours in mice with disabled immune systems, and identified 3,743 mutations in the genes of the tumour cells. They then narrowed down their focus onto a few mutated genes whose altered proteins seemed most likely to trigger immune system attacks. One of the mutated proteins, an altered form of spectrin-beta2, was seen in all tumour cells that the immune system attacked, but not in the cells that were ignored. The scientists cloned this mutant gene and put it into mouse tumour cells that lacked the mutation. On transplanting into mice with normal immunity, the tumour cells that made the mutant protein were destroyed by immune cells.

Dr. Schreiber explains the spectrin-beta2 mutation identified in the study as a red flag to the immune system. Its presence usually leads the immune system to assault cancer cells without any prompting from immunotherapy. He and his team are currently sequencing DNA in tumours grown from mice with normal immune systems to see if they can identify mutations that are not as readily discernible to the immune system. The idea is to make a vaccine that helps the immune system recognize and attack some of these mutated proteins, he says. “Therapeutically, that could be very helpful.”

Synthetic molecules that store, replicate genetic information

Researchers in the United Kingdom have created synthetic molecules that are capable of storing and replicating genetic data. A research group led by Dr. Philipp Holliger at the Medical Research Council’s Laboratory of Molecular Biology (LMB), created the first synthetic molecules that, alongside the natural molecules DNA and RNA, are capable of storing and replicating genetic information. The scientists modified enzymes, which in nature synthesize and replicate DNA, to establish six new genetic systems based on synthetic nucleic acids. These have the same bases as DNA but the ribose linkage between them is replaced by quite different structures. In accomplishing this, the scientists showed that there is no functional constraint limiting genetic information storage to RNA and DNA. Therefore, this finding has implications for the fundamental comprehension of life on Earth. As other informational molecules can be vigorously synthesized and replicated, the emergence of life on Earth is likely to reflect the abundance of RNA (and DNA) predecessors of Earth in its earliest stages.

One of the practical applications of the techniques developed by the investigators is likely to be the development of functional nucleic acids, called aptamers, with therapeutic, diagnostic and analytic applications. Aptamers can have a number of significant advantages over the current small molecule and antibody-based therapies. For example, they bind their target molecule with high specificity (like antibodies) but being smaller, they are expected to have better tissue penetration. They have low toxicity and immunogenicity, and they can be chemically modified to improve their stability and pharmacokinetic characteristics.

The new hexitol nucleic acid (HNA) genetic system developed by the LMB researchers efficiently produces molecules that are less susceptible to enzymatic degradation and are better suited for therapeutic use. The development of new aptamers could be useful in the diagnosis and treatment of cancers, haematologic, ocular and inflammatory conditions, and other diseases. The research team had the collaboration of scientists from Catholic University, Belgium, the Centre for Evolutionary Medicine and Informatics of Arizona State University, the United States, and the Nucleic Acid Centre of the University of Southern Denmark.

Transformational fruit fly genome catalogue completed

Scientists looking for more insight into predicting how genes affect an animal’s physical or behavioural traits now have a reference manual that should speed gene discoveries in everything from pest control to personalized medicine. Genetics researchers with North Carolina State University, the United States, teamed with scientists from across the globe to describe the new reference manual – the Drosophila melanogaster Reference Panel, or DGRP. Dr. Trudy Mackay, a professor of genetics and one of the lead authors, says that the reference panel contains 192 lines of fruit flies that differ enormously in their genetic variation but are identical within each line, along with their genetic sequence data. These resources are publicly available to researchers who study quantitative traits, or characteristics that vary and are influenced by multiple genes, for instance, traits like aggression or sensitivity to alcohol. Dr. Mackay expects the reference panel will help researchers studying anything from animal evolution to animal breeding to fly models of disease.

“Each fly line in the reference panel is essentially genetically identical, but each line is also a different sample of genetic variation among the population,” Dr. Mackay says. “So the lines can be shared among the research community to allow researchers to measure traits of interest.” In general, many genes were associated with three quantitative traits studied in fruit flies – resistance to starvation stress, chill coma recovery time and startle response – and that the effects of these genes were quite large. “Now we understand the genetic differences responsible for individual variation, or why one strain of flies lives longer or is more aggressive than another strain,” Dr. Mackay says.

Gene therapy effective in inherited blindness patients

Gene therapy for congenital blindness has shown success, with researchers further improving vision in three adult patients previously treated in one eye. After receiving the same treatment in their other eye, the patients became better able to see in dim light, and two were able to navigate obstacles in low-light situations. The treatment triggered no immune reaction. The current research conducted in the United States targeted Leber congenital amaurosis (LCA), a group of hereditary retinal diseases in which a gene mutation impairs production of an enzyme essential to light receptors in the retina. The reserch team was able to measure improvements objectively in light sensitivity, side vision and other visual functions, reported study co-leader Dr. Jean Bennett, F.M. Kirby professor of ophthalmology at University of Pennsylvania School of Medicine.

The study team injected patients with a vector (genetically engineered adeno-associated virus) which carried a normal version of a gene called RPE65 that is mutated in one form of LCA. The patients had earlier been subjected to the gene therapy on one eye, with notable and sustained results. While the results were encouraging, the researchers were apprehensive that readministering the vector in the untreated eye of the patients might stimulate an inflammatory response that could reduce the gains. While this was considered less likely than in other parts of the body, as the eyes are relatively isolated from the body’s immune system, this needed verification. As in the first study, retina specialist and study co-author Dr. Albert M. Maguire injected the vector into the untreated eyes of three patients at the Children’s Hospital of Philadelphia.

The research team found that the most notable improvements were in light sensitivity, such as the pupil’s response to light over a range of intensities. There were no safety problems and no significant immune responses. There was even an unexpected benefit – the functional magnetic resonance imaging (fMRI) results displayed improved brain responses not just in the newly injected eye, but in the first one as well. Dr. Bennet says that the research holds promise for using a similar gene therapy approach for other retinal diseases.

Genetic cause of Hamamy syndrome discovered

Scientists have identified the genetic cause of a birth defect known as Hamamy syndrome. The work by scientists from A*STAR Institute of Medical Biology (IMB), Singapore, in collaboration with scientists in Jordan, Turkey, Switzerland and the United States holds new insights into common ailments such as heart disease, osteoporosis, disorders related to blood and possibly, sterility. Hamamy syndrome is a rare genetic disorder, which is marked by abnormal facial features and defects in the heart, bone, blood and reproductive cells.

The international team of scientists pinpointed the genetic erroe to be a mutation in a single gene called IRX5. This is the first time that a mutation in IRX genes – a family of transcription factors that is highly conserved in all animals, and is found in humans as well – has been discovered in man. Using a frog model, the scientists demonstrated that IRX5 organizes cell movements in the developing fetus that underlie head and gonad formation. Ms. Carine Bonnard, PhD student at IMB and the first author of the paper, suggests that IRX5 is critical for development in the womb as well as for the function of many organs in our adult body. “This discovery of the causative gene is a significant finding that will catalyze research efforts into the role of the IRX gene family and greatly increase our understanding of human health, such as bone homeostasis, or gamete formation, for instance,” she added.

Body clock genes unravelled

Professor Chris Liddle, from the University of Sydney Westmead Millennium Institute for Medical Research, Australia, worked with a team from the Salk Institute, the United States, to demonstrate the importance of circadian receptors found in the brain and the liver. The circadian ‘clock’ controls alertness, appetite, sleep timing and hormone secretions. While the brain clock is mainly cued by light, the other clocks are cued by factors such as exercise and diet as well as receiving nerve and hormone signals from the central clock in the brain, the researchers said. They were able to show that the receptors in the liver were important in controlling the metabolism of fats and other genes related to diet, nutrition, digestion and energy expenditure. “We have now shown that these receptors in the body's tissues do not have a peripheral role but are core components for setting our body clock that we can potentially use drugs on,” Professor Liddle said.


First custom-designed protein crystals created

At University of Pennsylvania, the United States, chemists have used computational methods to create the first custom-designed protein crystal. The researchers’ success bodes well for the technique’s use in better understanding proteins’ make-up or their self-assembling properties in making new materials with unique properties.

Scientists employ crystals, which consist of many copies of a single protein lined up and stacked together, to determine protein structures. By irradiating the crystal with powerful X-rays, they can measure the way the light diffracts off the atoms and piece together the protein’s 3-D shape and composition. However, since most proteins don’t naturally crystallize, making crystals for diffraction studies is a laborious hit-or-miss process. Professor Jeffrey G. Saven, who conducted the current research together with his collegues, calls designing proteins “a complicated symphony of intermolecular interactions”. To tackle the tremendous number of variables involved and to search through potential proteins for ones that could crystalize into their target, the researchers developed a theoretical method and computer algorithm. They targeted a crystal built using a relatively small protein containing a sequence of 26 amino acid positions.

The researchers assigned specific amino acids to eight of the positions, but, with 18 different types of amino acid to choose from for each of the remaining 18 slots, the algorithm addressed more than 1,022 potential combinations. On top of that, the researchers had to account for other characteristics, such as the spacing between proteins and their relative orientation, multiplying the already astronomically large number of possibilities. Maximizing the efficiency of the search was thus a priority. The scientists synthesized the steps, doing both the characterization of structure and the sequence at the same time. After a day’s computation, the researchers’ algorithm produced a handful of promising candidates. Beyond presenting multiple candidates, the computational approach has the advantage of finding proteins that will produce diffraction-quality crystals. The candidate proteins began to crystalize within hours, a process that would normally take weeks or months. “With this technique, we can explore what those interactions are or how we might take an existing protein and engineer those interactions so that we get much better structures,” Prof. Saven said.

Protein critical for tissue regeneration discovered

A flatworm known for its ability to regenerate cells is shedding more light on how cancer could be treated and how regenerative medicine could better target diseases, say researchers at University of California-Merced (UC Merced), the United States. Dr. Néstor Oviedo, a professor of biology, has shown that signalling by Target of Rapamycin (TOR) – a protein found in humans and most other mammals – is crucial for the unique tissue regeneration in tiny flatworms called planaria. Disabling the protein prevents regrowth in them, a sign that disabling it in abnormal cells could prevent the growth of a cancer. Researchers have recognized that TOR plays a role in cancer, aging and degenerative diseases, but how it works was not understood.

For this study, Dr. Oviedo’s lab disabled the TOR protein in planaria and then amputated parts of the flatworm. Under typical circumstances, the organism would be able to repair itself. But the scientists discovered that the planaria’s stem cells recognized they needed to regrow tissue but were unable to regenerate it in the right place and instead formed tissues in abnormal places. Additionally, the planaria with the disabled protein were unable to grow, even if nutrients were available. Understanding TOR and its role in regulation could lead to, besides stopping cancer, the development of medicines to encourage tissue regeneration and to fight degenerative diseases, such as Alzheimer’s.

Two new blood types identified

Blood types A, B, AB and O are all well known. But how about the Langereis or Junior blood types? Most people would not have heard of these. Yet, this knowledge could be “a matter of life and death,” says biologist Dr. Bryan Ballif at University of Vermont, the United States. While blood transfusion problems due to Langereis and Junior blood types are rare worldwide, several ethnic populations are at risk, Dr. Ballif notes. “More than 50,000 Japanese are thought to be Junior negative and may encounter blood transfusion problems or mother-foetus incompatibility,” he writes.

As part of the international effort, Dr. Ballif and his colleagues discovered two proteins on red blood cells responsible for these lesser-known blood types. They identified the two molecules as specialized transport proteins named ABCB6 and ABCG2, taking the number of proteins responsible for a basic blood type to 32. Both of the newly identified proteins are also associated with anticancer drug resistance, and hence the findings may also have implications for treatment of breast and other cancers. The rejection of donated tissue, organ or blood that sometimes occurs might also have something to do with these proteins. After the protein identification, Dr. Lionel Arnaud and his team at the French National Institute for Blood Transfusion in Paris conducted cellular and genetic tests confirming that these proteins were responsible for the Langereis and Junior blood types.

Mapping proteins key to human health and immune system

Proteins are the ultimate transformers able to splice and switch roles and functions within the human body. But when these changes go wrong, diseases such as cancers and arthritis can result, says Dr. Chris Overall from Canada’s University of British Columbia. Dr. Overall’s groundbreaking research has led to substantive understanding of immune responses controlled by a family of enzymes called metalloproteinase.

Dr. Overall and his team discovered a protein that acts like a molecular beacon or a green traffic light capable of directing white blood cells – or leukocytes – to the site of injury or bacterial infection, such as gingivitis or periodontitis. In the process, they found that instead of just chewing up and destroying the collagen matrix, these enzymes were also “biting off” the first four amino acids at the end of the molecule. This resulted in a profound change in the behaviour of the protein, effectively turning the green traffic signal to red, and stopping the cascade of leukocytes to the site of inflammation. “Without this off signal, inflammation becomes chronic and causes destruction of cells and tissues,” Dr. Overall says.

The scientists have also shed light on “moonlighting” proteins. These proteins show up in unexpected places within a cell, or are intracellular proteins that venture outside a cell, but take on completely different functions depending on their new homes. What causes these proteins to suddenly change roles can be traced to their start and end points, or their “termini”, says Dr. Overall. He explains that specialized proteins – enzymes called proteases – have the job of precisely cutting into proteins. In so doing, new termini are generated and often start to perform new functions depending on the nature of their new ends. The termini at the end of a protein can have distinct jobs that are often critical for the function of the whole protein.

Protein prevents DNA damage in the developing brain

Scientists at St. Jude Children’s Research Hospital in the United States have rewritten the job description of the protein TopBP1 after demonstrating that it guards early brain cells from DNA damage that might foreshadow later problems, including cancer. The researchers showed that cells in the developing brain require TopBP1 to prevent DNA strands from breaking as the molecule is copied prior to cell division. They also noted that stem cells and immature cells known as progenitor cells involved at the beginning of brain development are more sensitive to unrepaired DNA damage than progenitor cells later in the process. Although more developmentally advanced than stem cells, progenitor cells retain the ability to become one of a variety of more specialized neurons.

“When we selectively knocked out TopBP1 in mice, the amount of DNA damage we saw suggests that TopBP1 is likely to be a tumour suppressor,” said Dr. Peter McKinnon, a geneticist and senior author of the paper. The researchers tracked the impact of TopBP1 loss in progenitor cells at different stages in the developing mouse brain. The damage was most severe when the protein was knocked out in early progenitor cells. These rapidly dividing cells yield the next generations of progenitor cells that give rise to structures in the cortex involved in memory, vision, movement and sensation. When TopBP1 was silenced in the early progenitor cells, the cortex never developed. When TopBP1 was knocked out a day or two later in progenitor cells responsible for completing brain and nervous system development, the defects were less severe. The progenitor cells that were created following the loss of TopBP1 were equally riddled with broken strands of DNA. In both the early and later progenitor cells, unrepaired DNA damage switched on the p53 gene that activated the cell’s suicide pathway.

Researchers used low-dose radiation to show that early progenitor cells were more sensitive to the DNA strand breaks than were progenitor cells created a day or two later. Although the cells suffered comparable damage, the damage was more likely to induce cell suicide in the earliest progenitor cells, indicating the likelihood of a different threshold to DNA damage in the early-born progenitors. TopBP1 is not the only protein responsible for repairing broken DNA strands, but this study suggests it plays a unique role. When researchers turned off two other key repair factors, the proteins Lig4 and Xrcc1, in the cortex of developing mice, the loss resulted in much less severe defects than when TopBP1 was lost.

Speeding up drug discovery with 3-D mapping of proteins

A new method for rapidly solving the 3-D structures of a group of proteins known as integral membrane proteins may speed drug discovery by providing scientists with precise targets for new therapies. The technique, developed at the Salk Institute for Biological Studies, the United States, provides a shortcut for determining the structure of human integral membrane proteins (hIMPs), molecules found on the surface of cells that serve as the targets for about half of all current drugs. Knowing the exact 3-D shape of hIMPs allows drug developers to understand the precise biochemical mechanisms by which current drugs work as well as to develop new drugs that target the proteins. “The very limited information on the shape of human membrane proteins hampers structure-driven drug design, but our method should help address this by dramatically increasing the library of known hIMP structures,” says Dr. Senyon Choe, a professor in structural biology and lead author of the paper.

Integral membrane proteins are attached to the membrane surrounding each cell, serving as gateways for absorbing nutrients, hormones and drugs, removing waste products, and allowing cells to communicate with their environment. Many diseases including cancer, heart disease and Alzheimer’s have been linked to hIMP malfunctioning, and a wide range of drugs target these proteins. Given a blueprint of the 3-D structure of a hIMP involved in a specific disease, drug developers could focus solely on molecules that are most likely to interact with the target hIMP, thus saving time and expense.

To side-step the difficulty in harvesting hIMPs, the scientists created an outside-the-cell environment, called cell-free expression system, to synthesize the proteins. They used a plexiglass chamber that contained all the biochemical elements necessary to manufacture hIMPs as if they were inside the cell. This system provided the researchers with enough of the proteins to conduct structural analysis. The cell-free method also allowed them to easily add labelled amino acids into the biochemical stew, which were then incorporated into the proteins. These amino acids gave off telltale structural clues when analysed with nuclear magnetic resonance spectroscopy. Prior methods used to take up to a year to determine a single protein structure, but using their new method, the Salk scientists determined the structure of six hIMPs within just 18 months. They have already identified 38 more hIMPs that are suitable for analysis with their technique, and expect it will be used to solve the structure for many more.

Lack of cell adhesion protein paves the way for breast cancer

A protein that is deficient in some types of breast tumors has been linked to the formation of desmosomes, the molecular complexes of cell adhesion and linking proteins that attach cell surface adhesion proteins to intracellular keratin cytoskeletal filaments. Desmoglein and desmocollin, the cell adhesion proteins of desmosome, are members of the cadherin family of cell adhesion molecules.

A protein called Perp (TP53 apoptosis effector) is known to have a role in stratified epithelial integrity and cell-cell adhesion by promoting desmosome assembly. In the current study, scientists at Stanford University, the United States, set out to explain why mice genetically engineered to lack the gene for Perp production suffered from severe blistering of the epidermis and oral mucosa and how such inflammatory response was linked to breast tumour formation.

Perp protein was expressed in the mammary epithelium, where it co-localized with desmosomes, the researchers reported. Perp loss affected mammary epithelial homeostasis by causing the accumulation of inflammatory cells around mature mammary epithelium. Reduced Perp expression was noted in many human breast cancer cell lines compared with untransformed cells, and Perp-deficiency promoted the development of mammary cancer in mouse model. Senior author Dr. Laura Attardi, an associate professor of radiation oncology, said, “Perp deficiency caused defects in desmosomal protein expression in breast epithelial cells,” adding that she also found that breast cancer cells had abnormally low levels of Perp.

Proteins egg on aggressive cancer metamorphosis

The mere presence of RalA and RalB seems to generate massive amounts of cellular trouble leading to aggressive versions of prostate, bladder and skin cancer, report researchers at University of Colorado Cancer Centre, the United States. The scientists noted that when both proteins are present, cancer cells in petri dishes evolve towards more aggressive varieties of cancer. And they explain why. The scientists determined that the presence of the proteins sets in motion a number of genetic and gene expression transformations that, in turn, may be driving the aggressive cancer evolutions. They looked at bladder, prostate and the squamous cell carcinoma skin cancer, and found that gene panels affected by both proteins in these cancers easily predicted both the stage of the cancer and survival prospects. It was the signature of other genes changed by RAL activity in the cells predicted aggressive cancer characteristics, said senior author Dr. Dan Theodorescu, Director of the University of Colorado Cancer Centre.


Engineered stem cells seek out and kill HIV in mice

A research team at University of California-Los Angeles (UCLA) have shown that genetically engineered human stem cells can attack cells infected with human immunodeficiency virus (HIV) in a living organism, effectively suppressing the virus.

In an earlier study, to solve the issue of inadequate quantities of “killer” T cells – CD8 cytotoxic T lymphocytes that help fight infection – needed to eliminate the virus from the body, the researchers had cloned the T cell receptor and used this to genetically engineer human blood stem cells. They then placed the engineered stem cells into human thymus tissue that had been implanted in mice. The engineered stem cells developed into a large population of mature, multi-functional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. In the current study too, the scientists similarly engineered human blood stem cells and found that the cells can form mature T cells to attack HIV in tissues of a humanized mouse model where the virus resides and replicates.

In tests on the mice’s peripheral blood, plasma and organs conducted two weeks and six weeks after introducing the engineered cells, the researchers found that the number of CD4 “helper” T cells – which become depleted following HIV infection – increased, while levels of HIV in the blood diminished. CD4 cells are white blood cells that are a key component of the immune system, helping to fight off infections. These results indicated that the engineered cells were capable of developing and migrating to the organs to fight infection there. “We believe that this is the first step in developing a more aggressive approach in correcting the defects in the human T cell responses that allow HIV to persist in infected people,” said Dr. Scott G. Kitchen, lead investigator and assistant professor of medicine at UCLA David Geffen School of Medicine.

Conversion of scar tissue into beating heart muscle

In the United States, scientists at the Gladstone Institute of Cardiovascular Disease of University of California-San Francisco (UCSF) have announced a research breakthrough in mice that one day may help doctors restore human hearts damaged by heart attacks – by converting scar-forming cardiac cells into beating heart muscle. Dr. Li Qian, along with researchers in the laboratory of Dr. Deepak Srivastava, accomplished this transformation in mice. “The damage from a heart attack is typically permanent because heart-muscle cells – deprived of oxygen during the attack – die and scar tissue forms,” said Dr. Srivastava, who directs cardiovascular and stem cell research at Gladstone. The new results offer proof of concept that non-beating cells can be reprogrammed directly into beating, fully functional heart cells to restore the heart after a heart attack.

In laboratory experiments with mice that had experienced a heart attack, the researchers delivered three genes that normally guide embryonic heart development – together known as GMT – directly into the damaged region. Within a month, non-beating cells that normally form scar tissue transformed into beating heart-muscle cells. Within three months, the hearts were beating even stronger and pumping more blood. “This research may result in a much-needed alternative to heart transplants – for which donors are extremely limited. And because we are reprogramming cells directly in the heart, we eliminate the need to surgically implant cells that were created in a petri dish,” stated Dr. Qian. The scientists will now replicate these experiments and test their safety in larger mammals.

New technique using stem cells revives damaged eye

Treating burns-related blindness using limbal stem cells harvested from the undamaged eye of the same patient has become more cheap, easy and safe, thanks to a pilot study on “simplified technique of limbal transplantation (SLET)”, conducted on six patients by L.V. Prasad Eye Institute, India. There are currently two ways of using limbal stem cells to cure blindness caused by burns. One is to transplant the stem cells directly to the blind eye. The other cultivated limbal epithelial transplantation (CLET) technique removes a 2 mm × 2 mm portion of the limbus containing the stem cells and increases the cells in the laboratory before transplanting them to the damaged eye. Both methods are good at restoring vision in the damaged eye, but they have their disadvantages.

In the direct transplantation known as conjunctival limbal autografting (CLAU), almost 50 per cent of the limbus has to be removed from the healthy eye. Excess removal of stem cells from the healthy eye could permanently damage it, and at present, there is no way of knowing the amount of limbal stem cells in an undamaged eye, says Dr. Virender S. Sangwan, who heads the Cornea and Anterior Segment Services. Doctors would come to know of the “deficiency” in that eye only two to three months after the operation. CLET is a safer alternative in this respect. While this procedure is safer, it is expensive and patients have to visit the hospital twice, one to remove the limbus and the other to transplant the expanded stem cells.

SLET, the new technique developed recently by Dr. Sangwan and his team, in collaboration with Dr. Sheila MacNeil at the University of Sheffield, the United Kingdom, combines the best of both methods. Only a small portion of the tissue is taken from the healthy eye and the stem cell expansion takes place in the damaged eye itself. Consequently, the healthy eye is not damaged, the procedure costs half that of CLET and there is less risk of contamination. The simple procedure takes about an hour to perform. The damaged eye is first cleaned and an amniotic membrane is pasted on the cornea using biological glue. The 2 mm × 2 mm limbal tissue harvested from the healthy eye is then cut into small pieces and placed on the membrane. Glue is then applied on the cut limbal tissue so that it sticks to the membrane. The eye is then bandaged using soft contact lens. The amniotic membrane acts as a scaffold on which the stem cells grow and expand.

The Achilles’ heel of life-threatening malaria parasites

Scientists in the United Kingdom have identified a link between different strains of malaria parasites that cause severe disease, opening a way that could help treat life-threatening cases of the infection. Researchers from the University of Edinburgh – working with collaborators from Cameroon, Mali, Kenya and Gambia – have identified a key protein that is common to many potentially fatal forms of the condition. They found that antibodies that targeted this protein were effective against the severe malaria strains. The protein has sticky properties that enable it to bind to red blood cells and form dangerous clumps that can block blood vessels. These clumps, or rosettes, can cause severe illness, including coma and brain damage.

Once in the bloodstream, malaria parasites are able to alter the protein molecules on their surfaces to evade attack by the immune system. These surface proteins are usually poor targets for treatment because they are highly variable between different malaria parasite strains. In the new study, the researchers tested antibodies against parasites collected from patients. They found that the surface proteins of rosette-forming parasites and found a common factor that could be targeted with antibodies.

World’s first kidney stem cells developed

Researchers at Monash Immunology and Stem Cell labouratories at Monash University, Australia, have found a way that may shorten the path to producing kidney cells. The researchers started with mature human kidney cells and wound back their developmental clock to a more embryonic state, instead of starting with embryonic stem (ES) cells derived from surplus human embryos. These induced pluripotent stem (iPS) cells have properties similar to ES cells. They multiply without limits and produce different types of cells. Researchers are, however, hoping to retain a memory of their origins and find their own way back on the convoluted route to becoming kidney cells.

From a collage of human kidney tissues with some 26 different cell types, Dr. Sharon Ricardo, an associate professor and one of the authors of the study, had to select a single type of cell to transform into a stem cell. She chose the mesangial cell, which plays the key role in filtering wastes and is also the one most often damaged in kidney disease. The researchers succeeded in producing the world’s first kidney-derived iPS cells, which they now plan to put to work. If they are successful in producing copious amounts of healthy mesangial cells, they might be able to slot them back into a diseased kidney to repair it.


Breakthrough on salt-tolerant wheat

In Australia, a team of researchers at University of Adelaide’s Waite Research Institute has bred salt tolerance into a variety of durum wheat that shows improved grain yield by 25 per cent on salty soils. Using crop breeding techniques without genetic modification and working with Plant Industry scientists from Commonwealth Scientific and Industrial Research Organization (CSIRO), the researchers introduced a salt-tolerant gene into commercial durum wheat, with spectacular results shown in field tests. The research is the first of its kind in the world to fully describe improved salt tolerance in an agricultural crop, from understanding the function of the salt-tolerant genes in the lab to demonstrating increased grain yields in the field.

Scientists Dr. Matthew Gilliham of the Waite Research Institute and Dr. Richard James and Dr. Rana Munns of CSIRO Plant Industry, along with their colleagues, discovered the new salt-tolerant gene TmHKT1;5-A in an ancestral cousin of modern-day wheat, Triticum monococcum. TmHKT1;5-A works by excluding sodium from the leaves. The gene produces a protein that removes sodium from the cells lining the xylem, the pipes plants use to move water from their roots to their leaves. Field trials were conducted at sites across Australia. “Importantly, there was no yield penalty with this gene,” Dr. James says. Under standard conditions, the modified wheat containing the salt-tolerance gene performed the same in the field as durum that did not have the gene. But under salty conditions, it outperformed durum wheat, with up to 25 per cent increased yields.

World’s first ‘handmade’ cloned transgenic sheep

In China, scientists from BGI, the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (CAS), and Shihezi University, Xinjiang province, made a significant breakthrough in animal cloning by producing the world’s first transgenic sheep produced using a simplified technique called handmade cloning. The transgenic sheep, named ‘Peng Peng’ after the identical given names of the two cloners, weighed 5.74 kg, said Dr. Yutao Du, Director of BGI Ark Biotechnology Co. Ltd. (BAB), one of BGI’s affiliates focusing on large-scale production of transgenic and cloned animals. “Peng Peng is developing normally and appears healthy,” she added.

The cloning may result in improved meat quality by increasing the unsaturated fatty acid content. The scientists say that a gene associated with w-3 poly unsaturated fatty acid (w-3PUFA) – essential fatty acids for humans – was successfully transferred into Peng Peng. “With each new species cloned, we learn more about the possible contribution of HMC to improve the health of animals and humans,” said Dr. Du.

Cloning suffers from general inefficiency – only a small fraction of the reconstructed embryos developing into healthy offsprings – and other operational difficulties. Hence, the scientists used an innovative simplified technique called ‘Handmade Cloning (HMC)’, with simplified procedures, lower costs, less demand for sophisticated equipment and higher production efficiency. Donor cells were collected from a Chinese Merino sheep, and by genetic manipulation a transgenic cell line was established. After numerous attempts, the HMC system for sheep cloning was successfully established in October 2011. The transfer of the produced embryos has eventually led to the present achievement.

Tomato genome sequenced

The Tomato Genome Consortium (TGC) – a group of more than 300 scientists from 13 countries – has sequenced the genomes of the domesticated tomato and its wild ancestor, Solanum pimpinellifolium. This is expected to lower costs, and help making it better equipped to combat pests, pathogens, diseases and droughts that plague tomato growers. Together, the sequences provide the most detailed look yet at the tomato genome, revealing the order, orientation, types and relative positions of its 35,000 genes. The new sequences are expected to provide reference points that would help identify all important genes in tomato’s relatives in Solanaceae family, including potato, pepper and eggplant.

The sequences also offer insight into how the tomato has diversified and adapted to new environments. They show that the tomato genome expanded abruptly about 60 million years ago, at a time close to one of the mass extinctions. Subsequently, most of this genetic redundancy was lost. Some of the genes generated during that event survive till today and control some of the most appealing traits of tomato.

First complete genetic map of Miscanthus

Scientists in the United Kingdom and the United States have collaborated to complete the first high-resolution, comprehensive genetic map of Miscanthus (Miscanthus x giganteus), a promising bioenergy crop. The development results from the long-term collaboration between energy crop company Ceres Inc., California, the United States, and the Institute of Biological, Environmental and Rural Sciences (IBERS) at Aberystwyth University, Wales, the United Kingdom. The IBERS team created the collection of genetically related plants and Ceres then sequenced and analysed the DNA. Ceres researchers mapped all 19 chromosomes of Miscanthus, a cane-like grass that can be used as a feedstock for advanced biofuels, bio-products and biopower. The project involved generation and analysis of more than 400 million DNA sequences creating a blueprint of the genetics of the plant.

The researchers found 20,000 genetic markers among the massive quantity of data. More than 3,500 of these markers were utilized to generate the genetic map, and are valuable for crop improvement purposes. While Miscanthus has been grown on a limited scale across Europe for two decades, mainly for electricity generation, large-scale commercial production is not economically viable at this time due to high production costs and few commercially available cultivars. Ceres Chief Scientific Officer Dr. Richard Flavell says, “By defining the genetic diversity in our germplasm collections with the new DNA markers, we can more rapidly introduce important crop traits into our new, seed-propagated Miscanthus products.” said Flavell. Unlike the current Miscanthus variety that is vegetatively propagated, Ceres’ seeded types are reported to need significantly less time, effort and money to be bred for different environments and to be established by growers.

A new source of maize hybrid vigour

At the University of Illinois in the United States, Dr. Steve Moose, an associate professor of maize functional genomics and his graduate student Mr. Wes Barber think they may have discovered a new source of heterosis, or hybrid vigour, in maize. They have been looking at small RNAs (sRNAs), a class of double-stranded RNA molecules that are 20 to 25 nucleotides in length. “Hybrid vigour” refers to the increased vigour or general health, resistance to disease, and other superior qualities arising from the cross-breeding of genetically different plants.

The researchers sampled sRNAs from the seedling shoot and the developing ear of maize hybrids, two tissues that grow rapidly and program growth, to investigate how the sRNA profiles of these hybrids differed from those of their parents. In collaboration with Dr. Matt Hudson, an associate professor of crop sciences they analysed 50 million data points, and whittled it down to the most important ones. They found that differences are mainly due to hybrids inheriting distinct small interfering RNAs (siRNAs), a subset of sRNAs, from each parent. These siRNAs interfere with gene expression. They also found that hybridization does not create new siRNAs, but hybrids have a more complex siRNA population than their parents because they inherit distinct siRNAs from both parents. Moreover, the differences in parental siRNAs originated primarily from repeats, which are the result of retrotransposon activity. “We are not saying that genes are not important,” said Moose. “But probably the way corn properties are altered in the hybrid situation is mediated by the small RNAs in addition to the genes.”

New insight into how plants fight diseases

A breakthrough discovery in the United Kingdom that has shown how plants may defend themselves against pathogen attacks could hold the key to making crops more disease-resistant and to boosting food production. Science & Technology Facilities Council’s Central Laser Facility has developed a unique technique that has answered a question that puzzled scientists for many years – why certain plant cell proteins don’t move around as much as their counterparts in animal cells. By enabling the movement of molecules in living plant cells to be observed in real time for the first time, the new technique has revealed that the cell wall plays a crucial role in limiting the mobility of proteins produced when a plant is attacked. Specifically, it has shown that the cell wall allows these proteins to stabilize in the plasma membrane. This restricts their ability to move around and fight invading pathogens and so increases the plant’s vulnerability.


Biotechnology for Medicinal Plants: Micropropagation and Improvement

Plant-based medicines play an important role in all cultures. The identification of active principles and their molecular targets from traditional medicine provides an enormous opportunity for drug development. Using modern biotechnology, plants with specific chemical compositions can be mass propagated and genetically improved for the extraction of bulk active pharmaceuticals. Although there has been significant progress in the use of biotechnology, using tissue cultures and genetic transformation to investigate and alter pathways for the biosynthesis of target metabolites, there are many challenges involved in bringing plants from the laboratory to successful commercial cultivation. This book presents the latest advances in the development of medicinal drugs, including topics such as plant tissue cultures, secondary metabolite production, metabolomics, metabolic engineering, bioinformatics and future biotechnological directions.

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

Regenerative Medicine and Cell Therapy (Stem Cell Biology and Regenerative Medicine)

Therapeutic applications within regenerative biomedicine have gained great interest from a growing, multidisciplinary community of investigators in recent years, driven by the hope of finding cures for several diseases. Regenerative Medicine and Cell Therapy discusses cutting-edge science in the field of regenerative biomedicine and its therapeutic applications to various medical disorders through chapters written by renowned scientists. This will be a useful book for basic and clinical scientists, as well as to stem cell biology students entering the world of stem cells research. The new knowledge and research outlined in this book will help contribute to new therapies for a wide variety of diseases that are presently afflicting humanity.

Contact: Humana Press, 999 Riverview Drive, Suite 208, Totowa, NJ, 07512, United States. Tel: +1 (973) 256 1699; Fax: +1 (973) 256 8341; Website:


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