VATIS Update Biotechnology . Jan-Mar 2014

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Biotechnology Jan-Mar 2014

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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Scientists aim to reduce requirement for live animal testing

Biological scientists at Plymouth University, the United Kingdom, in collaboration with multinational pharmaceutical company, AstraZeneca, UK, are investigating the effectiveness of ‘virtual fish’ in establishing the toxicity and concentration of man-made chemicals. The University has previously perfected the technique of coaxing cells from the liver of rainbow trout and then manipulating them to form a three-dimensional spheroid. This ball of cells behaves much more like normal animal tissue than cells grown in traditional ways in the lab and so can give researchers a more accurate picture of how an animal’s body would respond to a chemical in the environment.

Now, using a grant approximately £600,000, they plan to further develop the technique with cells from the gills and gut of fish in a move which has the potential to reduce the number of live animals required for scientific research. The technique developed in Plymouth does not use live animals, and scientists believe just a few fish could generate enough cells for the amount of testing required, with the added bonus that the spheroids last significantly longer than other samples created in the lab, and so can be used for more detailed experiments.

“We have already demonstrated that using fish liver cells maintains basic biochemical functions, can metabolise environmentally relevant contaminants and therefore has the potential to replace whole animal tests,” said Awadhesh Jha, a Professor in the University’s School of Biological Sciences. “Since billions of cells from several different organs can be harvested from a single fish, it means that far fewer fish will be used in research, and those that are will not be used directly in experiments.” The three-year project commenced in March 2014 and research experiments will be conducted at Plymouth University in collaboration with AstraZeneca.

Field trial of genetically modified varieties to resume

The Genetic Engineering Appraisal Committee (GEAC), the Ministry of Environment and Forests, India, has revalidated the field trials of 11 varieties of genetically modified (GM) crops, including of maize, rice, sorghum, wheat, cotton and ground-nut. The move came after the Union Environment Minister Veerappa Moily did a u-turn on the views of his predecessor Jayanthi Natarajan, who had held up the permission for field trials, despite GEAC approval after a six-member Technical Advisory Committee (TEC) constituted by the Supreme Court had suggested an indefinite moratorium till a proper regulatory mechanism was in place. GEAC is a regulatory body under the environment ministry.

The field trials now include varieties of transgenic maize by Monsanto and Pioneer Overseas, the United States, sorghum varieties of Central Research Institute of Dryland Agriculture (CRIDA), India, and varieties of transgenic rice from the University of Calcutta and Mahyco, India. The GEAC has also cleared the field trials on some animal vaccines, sent to the department of animal husbandry for tests. Officials said, the TEC issue also figured that GEAC was not capable of clearing field trials when the matter was in court.

Officials said revalidation of field trial approvals was necessary as many of the conditions such as a No-Objection Certificate (NOC) from states had changed. In a related development, the Coalition for GM-free India has approached the Election Commission of India against any clearance for field trials, on the ground that it was done with an eye on the coming elections.

A platform to design cancer, autism drugs

TeraDiscoveries, the United States, has announced that it will use its Inverse Design software platform to help Egenix, USA, design new drugs against cancer and autism. The value of the collaboration was not disclosed. Egenix will provide funding and target data that will apply toward identifying and designing inhibitors for unspecified cancer indications and autism. Egenix plans to develop the drugs through Phase II clinical trials, with TeraDiscoveries retaining a minority stake in the two drugs.

Egenix’s cancer therapeutic technology is designed to block production of cancer promoting proteins and promote their apoptosis through small-molecule drugs that inhibit the protein translation initiation factors eIF4E and eIF2α. Egenix considers eIF4E and eIF2α to be compelling cancer therapeutic targets because both translation initiation factors regulate proteins that mediate multiple processes required for cancer growth and metastasis. Overexpression of eIF4E and eIF2α occurs frequently in multiple human cancers, including leukemia, lymphoma, melanoma, and cancers of the colon, lung and breast.

Inverse Design runs computational models to quickly scan a chemical space to find the strongest inhibitors of a specific biological target – inhibitors that also have good druggable properties and are expected to have low toxic side effects. Inverse Design includes filters for key drug properties such as toxic side-effect risk assessment, off-target effects as-sessment, synthesizability, solubility, and freedom to operate assessment. Through specialized filtering, the platform can also can assess if a molecule crosses the blood-brain barrier.

GE installed biomanufacturing platform in China

GE Healthcare has installed its FlexFactory™ biomanufacturing platform at JHL Biotech’s Research Center and manufacturing plant in Taiwan (Province of China). The manufacturing platform has followed current good manufacturing practices (cGMP) and became fully operational in the end of 2013. Designed to help manufacturers FlexFactory comprised of single-use technologies and associated process hardware as well as all necessary automation and control components for start-to-finish manufacturing of biopharmaceuticals.

FlexFactory will be used for cell line development, process development, and cGMP manufacturing in pre-clinical and early-stage clinical work. In addition, it will serve as a “proving ground” for JHL Biotech for technology transfer. GE Healthcare’s experienced team will validate equipment at the site and will train local JHL Biotech staff. JHL Biotech’s facility includes two 500L single-use bioreactors, with the option to expand to 4 if greater throughput is required.

FlexFactory enables JHL Biotech to develop manufacturing processes prior to launching full-scale manufacturing operations in its Taiwan facility and prior to its KUBio factory in Wuhan becoming fully operational in early 2015. Mr. Olivier Loeillot, General Manager, at GE Healthcare said, “Our offering of tools, technologies and services for biomanufacturing has strength in both breadth and depth. For JHL Biotech we have been able to take an approach which recognises the differing requirements of multiple sites, whilst at the same time allowing them to replicate processes.”

Singapore opens its biggest neuroscience institute

The National Neuroscience Institute (NNI), Singapore, in a joint venture with Duke-NUS Graduate Medical School, Singapore, has launched National Neuroscience Research Institute Singapore (NNRIS) to improve treatment and seek cure through research for brain and nervous system disorders such as stroke, Parkinson disease and dementia. The NNRIS will be Singapore’s largest institute specializing in neuroscience research, bringing together more than 200 neurologists, neuroscientists and research professionals from NNI and Duke-NUS to work in collaboration.

The institute will consolidate expertise from the two organizations’ neuroscience research programmes, integrate research resources for common use, as well as develop a new research facility for neurobehavioural experiments. These will yield a more targeted, focused approach to neurological research in Singapore. In light of Singapore’s rapidly ageing population where age-associated diseases like dementia, Alzheimer’s disease, Parkinson disease and stroke are on the rise, it is expected that the work of the NNRIS will play an integral role in helping to address neurologic disease management and treatment.

“NNRIS represents Singapore’s first concerted step to tackle neurological problems and to look for practical solutions for our patients in the face of our ageing population and the rising incidence of neurological diseases,” said Professor Lee Wei Ling, director, NNI. “It should form the national nucleus to drive novel initiatives with the ultimate objective of improving the quality of life for those affected with neurological disorders.” Successful collaborations under the NNRIS bring together clinicians in the hospital with neuroscientists.

Bionomics awarded as the ‘Innovative Asian Biotech’

Bionomics Limited, Australia, has been awarded as the Innovative Asian Biotech of the Year at BioPharma Asia Industry Awards, at the Suntec Convention and Exhibition Centre in Singapore. The citation underpinning the Innovative Asian Biotech of the Year award made reference to Bionomics’ ability to adopt innovative technologies to develop novel drugs. It is also acknowledged the company’s approach to drug development including the implementation of new processes, technologies or applications that achieve quantifiable and sustainable results.

Further, CEO & Managing Director Dr. Deborah Rathjen was awarded the Life Science Woman Executive of the Year award for her contribution to both the biopharma industry and society. Conference leaders cited achievement of excellent results while demonstrating high levels of professionalism. “Bionomics has continued on an upward trajectory over the past 12 months with milestones right across our pipeline. These awards recognise the dedication and hard work of our team and we expect to continue substantial progress moving forward,” said Dr. Rathjen.


Next generation stem cell reprogramming solution

Life Technologies Corporation, the United States, has extended its collaborative agreement with DNAVEC Corporation, Japan, to launch CytoTune™-iPS 2.0 Sendai Reprogramming Kit, the next-generation research technology that enables the most efficient method to develop induced pluripotent stem (iPS) cells from human somatic cells. The newest kit doubles the number of colonies that can be produced and represents the latest in a series of products that are planned from the collaboration. CytoTune™-iPS 2.0 Sendai Reprogramming Kit uses a benign RNA virus developed by DNAVEC to deliver the reprogramming factors and clears out of the cell after about five replication cycles. The technology helps overcome major hurdles associated with traditional reprogramming techniques, which are highly inefficient and can lead to unwanted genetic mutations since vectors must insert themselves in the host cell’s DNA to deliver their payload.

By extending its collaborative research agreement with DNAVEC Corp., Life Technologies plans to build on the success it’s forged through the broad adoption of the CytoTune™ technology. Under the agreement, DNAVEC will undertake early stage R&D to apply its Sendai virus technology to third- and fourth-generation tools for use within the reprogramming and stem-cell workflows. “This technology will provide revolutionary new tools to cell engineering research worldwide. We are excited about the initiation of a new collaborative development program with Life Technologies, which aims to develop new vectors and products.” said Mamoru Hasegawa, President of DNAVEC.

Efficient development of iPS cells provides highly sought-after advantages for the basic and translational research fields. Scientists who test existing or novel drugs in the hopes of treating specific conditions can have faster access to patient-derived, physiologically accurate cells for disease modeling studies. DNAVEC’s deep expertise in Sendai virus technology to develop breakthrough solutions is complemented by Life Technologies’ global distribution channels that can rapidly put these novel products in the hands of customers to accelerate research and the promise of stem cells.

Global prophylactic vaccine market to reach $2.2bn

According to a report from research and consulting firm GlobalData, the United States, the global prophylactic human papillomavirus (HPV) vaccine market value is forecast to experience moderate growth over the coming years, climbing from USD1.7 billion in 2012 to USD2.2 billion by 2022, at a Compound Annual Growth Rate (CAGR) of 2.6 percent. The company’s report states that out of the nine major markets (US, Canada, France, Germany, Italy, Spain, the UK, Japan and Australia), HPV vaccine sales in Canada and Australia are expected to grow at the largest CAGRs of over 9 percent during the forecast period. This will be driven by the launch of Merck’s V503 vaccine and the inclusion of males in routine HPV vaccine recommendations.

Mr. Claire Herman, Director of Infectious Disease and Cardiovascular and Metabolic Disorders, said, “Recognizing both the role of HPV in other non-cervical cancers and the benefits of herd immunity has led to a greater emphasis on vaccinating both males and females. A shift away from a sole focus on cervical cancer in females appears to have benefited Merck, as its Gardasil vaccine provides protection against two additional HPV types, which are responsible for genital warts in males and females.” However, the global market for prophylactic HPV vaccines is marked by substantial obstacles to growth, namely low coverage rates and fears over vaccine safety. Additionally, a major clinical unmet need regarding current HPV vaccines is the limited number of HPV types against which they protect.

Antibacterial collaboration to develop antibiotics

Roche, Switzerland, has announced that it will use Discuva’s, the United Kingdom, Selective Antibiotic Target IdentificatioN (SATIN) technology platform to discover and develop new antibiotics for infections caused by multi-drug resistant Gram-negative bacteria, under a collaboration that could generate $191 million-plus for the British biotech, the United Kingdom. Discuva will use SATIN on the bacteriocidal hits identified via high-throughput phenotypic screening of chemical classes which hit molecular targets distinct from those already known to interact with existing antibiotics. The screening will enable Discuva to identify both the molecular target(s) of each compound and all the corresponding potential resistance gene(s).

Information generated by SATIN will enable the company to prioritize chemical optimization of compounds deemed to have the best chance of clinical success. Under their worldwide collaboration and license agreement, Roche agreed to pay Discuva $16 million upfront, plus up to $175 million per product developed, based on achieving undisclosed development, commercialization and sales milestones. Discuva will also receive royalties on sales of products developed through its collaboration with Roche’s Pharma Research and Early Development (pRED). Those royalties can reach double digits if products are based on the company’s early-stage antibiotic programs.

Non-small cell lung cancer market value to touch $2.9 bn

The GBI Research, the United States, has revealed that the non-small cell lung cancer (NSCLC) therapeutics market value in the Asia-Pacific (APAC) region – Australia, China, India and Japan – is likely to increase at CAGR of 6.3 per cent during 2012-2019 to $2.9 billion by 2019 from $1.8 billion in 2012. Japan and China had the largest shares of the region’s NSCLC market in 2012, with 48.5 per cent and 41.5 per cent, respectively. Meanwhile, Australia and India had lower shares of 5.9 per cent and 4.1 per cent. Sravanthi Addapally, senior analyst at GBI Research, said that an ageing population and increasing number of NSCLC incident cases, especially in China and India, will be the main drivers behind the anticipated market growth.

Currently, the NSCLC pipeline is very strong, with a total of 290 active molecules in development, either as monotherapies or in combination with chemotherapy. Promising candidates in the late-stage clinical trials include second-generation Tyrosine-Kinase Inhibitors, such as Pfizer’s dacomitinib and Boehringer Ingelheim’s Gilotrif. This latter therapy is currently a pre-registration drug in Japan for Epidermal Growth Factor Receptor-positive patients. “In spite of many expected drug launches, growth in this treatment market is forecast to be marginal due to the dominant generic penetration of NSCLC drugs in India. A complex and lengthy regulatory pathway and limited reimbursement from national insurance programs in China, as well as regular price cuts in Japan, will also hinder further market expansion in the APAC region.” Addapally said.

EMD Millipore receives grant for liver treatment research

EMD Millipore, the Life Science division of Merck KGaA, Germany, has announced that they have received a $400,000 grant from the Massachusetts Life Sciences Center (MLSC), the United States, to fund a partnership with Promethera Biosciences, Belgium, whose mission is to discover, develop, and commercialize cell therapy products to treat liver diseases in an innovative way. Through this collaboration, EMD Millipore’s microfluidic technology will enable the researchers at Promethera to mimic the liver microenvironment long-term, allowing for increased consistency and scale-up potential for live cell models. Using liver stem cells provided by Promethera and EMD Millipore’s CellASIC® microfluidic cell culture platform, both organizations strive towards improved preclinical liver toxicity testing methods. Current methods for liver toxicity testing are limited by technical challenges that the CellASIC® platform can address.

“The partnership between EMD Millipore and Promethera Biosciences will help bring new health technologies to the market along with economic benefits for Massachusetts. No one country or region can address on its own the urgent health challenges that still face our global community, and we are pleased to be partnering with some of the world’s leading regions in life sciences innovation,” said Susan Windham-Bannister, President & CEO of MLSC.

A collaboration in the development of biosimilar drugs

Merck & Co., Inc. (MRK), the United States, and Samsung Bioepis Co., Ltd., has entered into an agreement to develop and commercialize multiple pre-specified and undisclosed biosimilar candidates. “The combination of Merck’s global com-mercial presence with Samsung Bioepis’ biologic development and manufacturing capabilities positions the two companies well to increase access to biosimilars to improve human health. We look forward to this collaboration and it’s potential to complement our expanding internal biologics portfolio,” said Rich Murray, senior vice president at Merck Research Laboratories.

Under the agreement, Samsung Bioepis will be responsible for preclinical and clinical development, process development and manufacturing, clinical trials and registration. Merck will be responsible for commercialization. Samsung Bioepis will receive an upfront payment from Merck, product supply income and will be eligible for additional payments associated with pre-specified clinical and regulatory milestones. Samsung Bioepis has been building the capabilities needed to develop high-quality biosimilars. With this development and commercialization agreement, Samsung takes a significant step toward becoming a major player in the biopharmaceutical industry.


Researchers sequence world’s first butterfly bacteria

For the first time ever, a team led by the University of Colorado (CU), the United States, has sequenced the internal bacterial makeup of the three major life stages of a butterfly species, a project that showed some surprising events occur during metamorphosis. The team, led by Tobin Hammer, used powerful DNA sequencing methods to characterize bacterial communities inhabiting caterpillars, pupae and adults of Heliconius erato, commonly known as the red postman butterfly. The red postman is an abundant tropical butterfly found in Central and South America.

The results showed the internal bacterial diversity of the red postman was halved when it morphed from the caterpillar to the chrysalis, or pupal stage, then doubled after the pupae turned into active adult butterflies. The study is important because communities of bacteria inhabiting other insects have been shown to affect host nutrition, digestion, detoxification and defense from predators, parasites and pathogens, said Hammer. A paper on the subject has been published in the journal PLOS ONE.

The collection of microorganisms on a single animal, collectively known as the microbiome, has become important because such bacterial groups have been found to affect metabolic and developmental processes from food digestion and vitamin synthesis to possible brain function. While the average human is made up of about 1 trillion cells, scientists now estimate each of us has a staggering 10 trillion bacteria – essentially 10 bacteria for every human cell. “People are starting to think about the microbiome of insects as targets for pest control, including insecticides, so we need to know what specific bacteria they contain and how they work,” Hammer said.

New research pathways treatments for malaria

A team of researchers led by investigators at Indiana University School of Medicine (IUSM), the United States, have reported that a newly identified protein and other proteins it interacts with could become effective targets for new drugs to control the parasite that cause toxoplasmosis. The discovery could also open new research pathways for treatments for malaria. The researchers determined that the protein, an enzyme called GCN5b, is necessary for the Toxoplasma parasite to replicate, so interfering with its activities could control the parasite. GCN5b is part of the molecular machinery that turns genes on and off in the parasite, working with other proteins that are more plant-like than their counterparts in humans.

“GCN5b is a very different protein than its human counterpart, and proteins it interacts with are not found in humans. That’s what makes this exciting – rather than just having one enzyme that we could go after, there could be a whole collection of associated enzyme components that could be potentially targeted for drug therapies to control this parasite,” said William J. Sullivan Jr., associate professor at IUSM.

In discovering that some of the proteins interacting with GCN5b are plant-like transcription factors – proteins that bind to DNA – the researchers filled in what had been a missing link explaining how the parasites control the process of turning genes on and off, known as gene expression. The plant-like transcription factors recruit the GCN5b enzyme complex to activate a wide variety of genes for expression. When the research team disabled the GCN5b complex, parasite replication swiftly came to a halt. The researchers have reported their findings in the journal PLoS Pathogens.

A chromosome therapy to correct a severe chromosome defect

Geneticists from the United States and Japan have joined forces in a quest to correct a faulty chromosome through cellular reprogramming. Their study has been published in the journal Nature, used stem cells to correct a defective “ring chromosome” with a normal chromosome. Such therapy has the promise to correct chromosome abnormalities that give rise to birth defects, mental disabilities and growth limitations. “In the future, it may be possible to use this approach to take cells from a patient that has a defective chromosome with multiple missing or duplicated genes and rescue those cells by removing the defective chromosome and replacing it with a normal chromosome,” said Anthony Wynshaw-Boris, professor at Case Western Reserve School of Medicine (CWRU SOM), the United States, who led this research.

Individuals with ring chromosomes may display a variety of birth defects, but nearly all persons with ring chromosomes at least display short stature due to problems with cell division. A normal chromosome is linear, with its ends protected, but with ring chromosomes, the two ends of the chromosome fuse together, forming a circle. This fusion can be associated with large terminal deletions, a process where portions of the chromosome or DNA sequences are missing. These deletions can result in disabling genetic disorders if the genes in the deletion are necessary for normal cellular functions.

The researchers observed that, after reprogramming, the ring chromosome 17 that had the deletion vanished entirely and was replaced by a duplicated copy of the normal chromosome 17. However, the terminal deletions in the other two patients remained after reprogramming. To make sure this phenomenon was not unique to ring chromosome 17, they reprogrammed cells from two different patients that each had ring chromosomes 13. These reprogrammed cells also lost the ring chromo-some, and contained a duplicated copy of the normal chromosome 13. “In theory, the way you could potentially correct a chromosome with deletions or duplications is to make a ring out of it and then get rid of the ring chromosome during reprogramming. Although, it may be useful to use this for tissue repair of birth defects and other abnormalities found in individuals with chromosomal abnormalities as techniques for regenerative medicine are developed in the future,” said Wynshaw-Boris.

Drug discovery potential of natural microbial genomes

Scientists at the University of California (UC), the United States, have developed a new genetic platform that allows efficient production of naturally occurring molecules, and have used it to produce a novel antibiotic compound. The study has been published in the journal PNAS, may open new avenues for natural product discoveries and drug development. According to lead investigator Bradley S. Moore, at UC, the findings demonstrate a “plug and play” technique to trigger previously unknown biosynthetic pathways and identify natural product drug candidates.

“In my opinion, the new synthetic biology technology we developed – which resulted in the discovery of a new antibiotic from a marine bacterium – is just the tip of the iceberg in terms of our ability to modernize the natural product drug discovery platform,” Moore said. Most natural antibiotics are complex molecules that are assembled by a special group of enzymes genetically encoded in the microbe’s chromosome and it’s difficult to grow the newly discovered ocean bacteria in the laboratory. The UC scientists harvested a set of genes predicted to encode a natural product from ocean bacteria, then used the synthetic biology technology to identify and test a totally new antibiotic – taromycin A – found to be effective in fighting drug-resistant MRSA.

Such microbes have the genetic capacity to biosynthesize a wide range of specialized compounds and researchers currently lack procedures to efficiently link genes with specific molecules. To help bridge this gap, the UC researchers developed a genetic platform based on transformation-associated recombination (TAR) cloning, which efficiently produces natural product molecules from uncharacterized gene collections. They applied the platform to yeast, targeting the taromycin gene cluster because of its high degree of similarity to the biosynthesis pathway of daptomycin, a clinically approved antibiotic used to treat infections caused by multi-resistant bacteria. This technique has the potential to unlock the drug discovery potential of countless new and mysterious microbes.

Unraveling a mystery in the ‘histone code’

Scientists at Cold Spring Harbor Laboratory (CSHL), the United States, have revealed a new layer of complexity in the ‘histone code’. Each cell in our entire body has exactly the identical DNA. A cell’s identification is identified by the subset of genes that it activates. When the genetic code carried in our DNA gives guidelines for cells to manufacture particular proteins, it is a next code that decides which genes are in reality activated in unique mobile kinds. This second code is carried by proteins that attach to DNA. The code-carrying proteins are known as histones. Researchers found that the slightest variation in a single histone protein can have remarkable outcomes on how the genes encoded in our DNA are utilised.

There are quite a few forms of histones, and modest versions in their structure permit them to complete distinct specialised features. Scientists have observed that a person histone, known as H3, comes in two subtypes, referred to as H3.1 and H3.3. These variants are found in very diverse areas in the genome: edition is discovered only in parts of the genome the place genes are not currently being activated model H3.3 is existing only in destinations the place genes are active. Researchers have long puzzled what it is about these two variants that accounts for their unique associations with genes – with inactive genes and H3.three with lively ones.

In a research paper posted in Science, a team led by CSHL Professor Robert Martienssen has announced that they have solved the mystery, exploiting exceptional areas of plant genomes. They have learned that a one amino acid big difference in the framework of histone H3.three enables it to provide as a variety of memory product for the cell, marking genes that need to continue to be lively. “This research also has implications for how the genetic materials is copied. We have discovered that replication (how DNA copies alone) and transcription (how DNA is copied into RNA) are controlled by the very same highly conserved histone. Therefore, these most fundamental properties of the genetic substance are controlled by our chromosomes,” said Martienssen.

Protective mutations for type 2 diabetes

An international team led by researchers at the Broad Institute and Massachusetts General Hospital (MGH), the United States, has identified mutations in a gene that can reduce the risk of developing type 2 diabetes, even in people who have risk factors such as obesity and old age. The results focus the search for developing novel therapeutic strategies for type 2 diabetes; if a drug can be developed that mimics the protective effect of these mutations, it could open up new ways of preventing this devastating disease.

Type 2 diabetes affects over 300 million people worldwide and is rising rapidly in prevalence. Lifestyle changes and existing medicines slow the progression of the disease, but many patients are inadequately served by current treatments. The first step to developing a new therapy was discovering and validating a “drug target” – a human protein that, if activated or inhibited, results in prevention and treatment of the disease. The study breaks new ground in type 2 diabetes research and guides future therapeutic development in this disease.

“This discovery underscores what can be accomplished when human genetics experts on both sides of the Atlantic come together to apply their craft to founder populations, enabling us to find rare mutations with large effects on disease risk,” said Kari Stefannson, CEO of deCODE genetics, Iceland. The work represents the fruits of an international collaborative effort among researchers from many universities and hospitals around the world.

Gene therapy a promising tool for cardiac regeneration

After a heart attack, there is often permanent damage to a portion of the heart. This happens, in part, because cardiac muscle cells are terminally differentiated and cannot proliferate after blood flow is blocked off to the heart. This partial healing can be attributed to heart disease being one of the leading causes of death. However researcher Scott Shapiro and his co-authors from the George Washington University (GW), the United States, have found that cardiac regeneration may be a possibility with gene therapy.

Shapiro and his research team first looked to small animals such as the zebrafish, which are able to regenerate heart tissue after a heart attack. This animal has a key protein at play, Cyclin A2 (Ccna2). “After seeing the effects of CCna2 in small animals, we began looking at the effects of the gene in larger animals, such as pigs,” said Shapiro, assistant professor of medicine at the GW School of Medicine and Health Sciences. “We delivered Ccna2 directly into the heart and found that pigs not only had improved cardiac function, but also found evidence of cellular regeneration.”

Ccna2 is a prenatal gene normally turned off in humans after birth. Shapiro believes using gene therapy as a tool for cardiac regeneration, optimized for humans, could lead to a viable treatment option for patients who suffer from myocardial infarction, or heart attack.


Bacterial superbug protein structure

A research team from Vanderbilt University Medical Center (VUMC), the United States, has deciphered the 3-D structure of a protein that confers antibiotic resistance from one of the most worrisome disease agents, a strain of bacteria called methicillin-resistant Staphylococcus aureus (MRSA), which can cause skin and other infections. The VUMC team’s findings may be an important step in combatting the MRSA public health threat over the next 5 to 10 years. By deciphering the shape of a key S. aureus protein – an enzyme called FosB that inactivates an antibiotic called fosfomycin – the researchers have set the stage to devising a therapeutic method to inhibit FosB and hence improve the efficacy of the antibiotic.

“Our hope is that now that we know the 3-D shape and overall function of the FosB protein, we will be able to design inhibitors of FosB that will enable fosfomycin to function appropriately as an antibiotic,” said Matthew K. Thompson, a researcher at VUMC. Identifying the FosB protein’s three-dimensional structure helps scientists understand that protein’s particular function. In particular, the new structural images of FosB, obtained by a technique called X-ray crystallography, provide insight into the functional role of a particular part of the protein’s shape called a binding loop. It appears to function like a door that opens and closes to allow the antibiotic to enter the active site of FosB.

In addition to providing new insight on the function of this S. aureus protein, the research has also produced new evidence for the role zinc might play in inhibiting FosB. This could impact restoring the efficacy of fosfomycin, leading to treatment for a variety of multi-drug-resistant pathogens. According to the U.S. Centers for Disease Control (CDC) and Prevention, MRSA poses a serious risk to public health. Studies show that about one in three people carry S. aureus in their nose, usually without any illness, and two in 100 people carry the methicillin-resistant version of the bacteria, though there is no data to show the total number of people who get MRSA skin infections.

Consequences of accumulated misfolded proteins

A recent research by the University of Southampton (Soton), the United Kingdom, has provided new insight into the consequence of accumulated ‘misfolded proteins’ in neurodegenerative disorders, such as Prion and Alzheimer’s disease. Prion and Alzheimer’s disease are protein misfolding brain diseases, where genetic mutations, or more commonly, interactions between an individual’s genetics and environmental influences cause functional proteins in neurons to become misfolded or misrouted. In these diseases, there is a progressive death of nerve cells in specific brain regions, which is associated with the increasing extracellular or intracellular accumulation of misfolded proteins. This leads to synapse degeneration and eventual loss of nerve cells and cognitive and behavioural conditions associated with the disease.

To increase the understanding of the disease mechanisms, the researchers, led by Dr. Ayodeji Asuni from Soton, compared prion disease brain tissue, which mirrors key features of Alzheimer’s disease, and the brain of control mice. They found that the degenerative process is paralleled by an increase in astrocytes – a major support cell in the brain – and four specific astrocytes-associated proteins: GFAP (structural protein), peroxiredoxin-6 (an antioxidant protein), EAAT-2 (glutamate transporter), and Clusterin (a chaperone protein) that are produced in greater amounts in response to the misfolding protein, perhaps to provide support and protection for neurons in the brain.

Current research has identified Clusterin as a biomarker for Alzheimer’s disease and Dr. Asuni’s team extended their investigation to address whether Clusterin changes in the brain could be detected in the blood; such a result would confirm Clusterin as a potential biomarker for brain disease. “In contrast to observations made in Alzheimer’s disease, the increased Clusterin expression in the brain was not reflected in the circulating levels of Clusterin in late-stage prion disease. So we caution against the assumption that plasma levels of Clusterin provide an alternate peripheral measure for the progression of brain degeneration. We believe the observations from our study in experimental conditions, in which potential confounds can be well controlled, will likely be of value in the interpretation of results from Alzheimer’s disease patients,” Dr. Asuni said.

Researchers found key proteins for electrical communication

Researchers from Cedars-Sinai Heart Institute, the United States, have found that six proteins – five more than previously thought – are responsible for cell-to-cell communication that regulates the heart and plays a role in limiting the size of heart attacks and strokes. The smallest of these proteins directs the largest in performing its role of coordinating billions of heart cells during each heartbeat. Together, the proteins synchronize the beating heart, the researchers determined. “We now know these proteins exist,” said Robin Shaw, the senior author of the study.

Until now, scientists had recognized just one protein involved in cell-to-cell communication that occurs through conduits known as “gap junctions.” The researchers identified five additional proteins that regulate the rapid flow of electrical communication signals, coordinating heart cells to produce a stable heartbeat. Through a phenomenon called “alternative translation,” the protein-making machinery in each cell can produce shorter proteins from the same gene that encodes the largest of the proteins. Biologists had known of the existence of alternative translation but had not completely understood its physiological relevance.

The researchers also have determined that a class of drugs known as “mTOR inhibitors” – those already used for immunosuppression in organ transplants – can affect alternative translation, changing the balance of proteins in hearts cells, increasing the amount of electrical coordination in the heart. The finding that mTOR inhibitors improve cell-to-cell communication indicates that this class of drugs could be useful to treat multiple disorders.

A 3-D picture of protein linked to brain disorders

Researchers at The Scripps Research Institute (TSRI) and Vanderbilt University, the United States, have created the most detailed 3-D picture yet of a membrane protein that is linked to learning, memory, anxiety, pain and brain disorders such as schizophrenia, Parkinson’s, Alzheimer’s and autism. “This receptor family is an exciting new target for future medicines for treatment of brain disorders. This new understanding of how drug-like molecules engage the receptor at an atomic level promises to have a major impact on new drug discovery efforts,” said P. Jeffrey Conn, director at Vanderbilt, with Raymond Stevens, a professor at TSRI.

The mGlu1 receptor, which helps regulate the neurotransmitter glutamate, belongs to a superfamily of molecules known as G protein-coupled receptors (GPCRs). GPCRs sit in the cell membrane and sense various molecules outside the cell, including odors, hormones, neurotransmitters and light. After binding these molecules, GPCRs trigger a specific response inside the cell. More than one-third of therapeutic drugs target GPCRs-including allergy and heart medications, drugs that target the central nervous system and anti-depressants.

“This work leveraged the unique strengths of the Vanderbilt and Scripps teams in applying structural biology, molecular modeling, allosteric modulator pharmacology and structure-activity relationships to validate the receptor structure,” said Colleen Niswender, an associate professor at the Vanderbilt. The findings show that mGlu1 possesses structural features both similar to and distinct from those seen in other GPCR classes, but in ways that would have been impossible to predict in advance.

Using fruit fly to treat brain injury

According to researchers at Duke University, the United States, a protein that controls the metamorphosis of the common fruit fly could someday play a role in reversing brain injuries. This protein directs both the early development and regrowth of the tiny branches that relay information from neuron to neuron. Known as dendrites, these thin structures that resemble tree branches are responsible for receiving electrical impulses that flash throughout the body.

“One of the major problems with the nervous system is that it doesn’t regenerate very well after injury. Neurons don’t multiply, so when they’re injured, there’s a loss of function. We’d like to know how to get it back,” said assistant professor Chay Kuo. Until now, researchers haven’t understood how Drosophila sensory neurons are able to create two separate dendrite branching patterns that successfully serve different kinds of sensory environments. The answer lies in the insect’s metamorphosis from larvae to adult. During this transition, Drosophila lose the neurons they won’t need for adult life. The remaining sensory neurons sever their dendrites and grow a completely different set. The regeneration process, which is controlled by the hormone ecdysone, is much like pruning a tree in spring to make room for new growth.

This research could potentially impact how science and healthcare think about and treat brain injuries. Currently, damaged neurons that have lost their dendrites are unable to properly communicate with their neighbors, rendering them nonfunc-tional. The problem could be reversed, by helping neurons modify their original developmental program and regrow new dendrites. “If we can influence this environmental control that changes the development program, it’s possible that we could get neurons to integrate and function better after injury,” Kuo said.


Vinegar kills tuberculosis and other mycobacteria

An international team of researchers from Venezuela, France, and the United States have reported in mBio®, the online journal of the American Society for Microbiology, that the active ingredient in vinegar, acetic acid, can effectively kill mycobacteria, even highly drug-resistant Mycobacterium tuberculosis. Acetic acid might be used as an inexpensive and non-toxic disinfectant against drug-resistant tuberculosis (TB) bacteria as well as other stubborn, disinfectant-resistant mycobacteria.

“Mycobacteria are known to cause tuberculosis and leprosy, but non- TB mycobacteria are common in the environment, even in tap water, and are resistant to commonly used disinfectants. When they contaminate the sites of surgery or cosmet-ic procedures, they cause serious infections. Innately resistant to most antibiotics, they require months of therapy and can leave deforming scars,” said Howard Takiff, head of the Laboratory of Molecular Genetics at the Venezuelan Institute of Scientific Investigation (IVIC), Venezuela.

While investigating the ability of non-TB mycobacteria to resist disinfectants and antibiotics, researchers stumbled upon vinegar’s ability to kill mycobacteria. Testing a drug that needed to be dissolved in acetic acid, they found that the control, with acetic acid alone, killed the mycobacteria. The team tested for the minimal concentrations and exposure times that would kill different mycobacteria and found that exposure to a 6% solution of acetic acid for 30 minutes effectively kills tuberculosis, even strains resistant to almost all antibiotics. “For now this is simply an interesting observation. Vinegar has been used for thousands of years as a common disinfectant, whether it could be useful in the clinic or mycobacteriology labs for sterilizing medical equipment or disinfecting cultures or clinical specimens remains to be determined,” said Takiff.

Cancer vaccine could use immune system to fight tumors

Researchers from Cincinnati Cancer Center (CCC) and University of Cincinnati (UC) Cancer Institute, the United States, have found that a vaccine, targeting tumors that produce a certain protein and receptor responsible for communication be-tween cells and the body’s immune system, could initiate the immune response to fight cancer. Principal Investigator John Morris at CCC, said a number of antitumor vaccines have shown promise for causing immune responses against tumor antigens to improve patient outcomes.

“Recently, human Interleukin-15 (IL-15) has entered clinical trials for treatment of patients with melanoma, a type of skin cancer, and renal cancer. In this study, we examined the effectiveness of a vaccination targeting tumors that produced IL-15 and its cell surface receptor called IL-15R-alpha and examined their ability to up-regulate (or increase) immune responses to tumor antigens,” Morris said. “We showed that the presence of both IL-15 with its receptor IL-15Ra increased the cell-surface production and secretion of IL-15, and in turn, stopped tumor cells from reproducing.”

Researchers used IL-15 to develop a whole tumor cell vaccine to target breast (TS/A) and prostate (TRAMP-C2) cancer cells in animal models; results showed that tumor cells stopped growing after the vaccine was introduced and that beneficial effects were enhanced further when IL-15Ra was co-produced by the vaccine cells. IL-15 is a powerful pro-inflammatory protein that can enhance immune responses. “Our findings suggest that genetically altering tumor cells to produce IL-15 and IL- 15Ra can cause and enhance immune responses to tumor antigens found in these tumor cells and can be used as a vaccine to target these antigens.” Morris said.

Researchers discover new target for dengue virus vaccine

Researchers at the University of North Carolina (UNC), the United States, have discovered a new target for human antibodies that could hold the key to a vaccine for the world’s most widespread mosquito-borne disease. Using an experimental technique new to the dengue field, researchers showed that a molecular hinge where two regions of a protein connect is where natural human antibodies attach to dengue 3 to disable it. The finding, published in the Proceedings of the National Academy of Sciences, shows that after primary infection most human antibodies that neutralize the virus bind to the hinge region. It’s the first study to demonstrate how these binding sites – composed of just 25 amino acids – can be genetically swapped out for amino acids from another dengue type without disrupting the integrity of the virus.

“This gives us a lot of insight into how human antibodies work, and there could be a lot of translational aspects to this; which could lead to a new way to create vaccines for other diseases,” said Aravinda de Silva, a professor at UNC. Dengue, which infects approximately 390 million people each year, is common in tropical and subtropical regions around the world. The virus, widespread in the United States territory of Puerto Rico, has also been confirmed in mainland south Florida and Texas. “The mosquitos that can carry dengue exist throughout the southeastern United States,” Baric said. “It’s just a matter of time before dengue virus reemerges in the South, making vaccines and therapeutics a critical long-term public health priority.”

De Silva along with Ralph Baric, a professor at UNC, are now working with vaccine developers at two pharmaceutical companies to test the effectiveness of potential dengue vaccines now in clinical trials. If these vaccines don’t bind to their molecular hinge, then the vaccines will likely prove less effective than researchers would like, especially over time. Both are using their results to study why antibodies bind to a specific epitope but not to other sites. Such information would lend even more insight into how to design effective vaccines. Also, their research could be translated into other fields in need of vaccines. “The general idea is that a complex protein-interaction site can now be moved from one virus to another,” de Silva said. For instance, an epitope from a virus like hepatitis C could be moved onto the live virus used in the measles vaccine. This new chimeric virus would simultaneously offer people protection against hepatitis C and measles.

Building a better model to understand pancreatic cancer

Cancer of the pancreas is usually not detected until it’s too late to cure. But precursor lesions that form in the pancreas and its ducts can signal the disease before it strikes, and when caught early enough, they can be prevented from progressing to become cancer. However researchers at the University of California, San Francisco (UCSF), the United States, have reported two breakthroughs in understanding those lesions and their role in pancreatic cancer, the development of the first mouse model that simulates a precursor lesion called intraductal papillary mucinous neoplasia (IPMN), and the identification of an enzyme, Brg1, that appears to help cause the formation of IPMN lesions while also suppressing another precursor lesion.

Matthew A. Firpo, associate professor at University of Utah, the United States, said, the research proves that epigenetics – changes in genetic activity caused by forces other than modifications in the DNA sequence, such as when genes are turned on or off – play a role in pancreatic ductal adenocarcinoma (PDA), the most common type of cancer of the pancreas. “These findings may provide an avenue for intervention in PDA, if we can understand the epigenetics.” This study not only represents a longstanding collaboration between the University of Utah and UCSF but also is a reflection of the transition in research from single investigators working on their own to highly collaborative studies with experts in many fields from different institutions.

With a five-year survival rate of just 4.4 percent, cancer of the pancreas is the fourth leading cause of cancer deaths. In 82 percent of cases, the disease is found when it’s too late to remove the tumor. Tumors that are smaller than 2 centimeters and haven’t metastasized are considered the best cases for surgery. When tumors are operable, the five-year survival rate approaches 40 percent. “As someone who researches pancreatic cancer, I think this discovery is significant because it de-fines mechanisms that lead to this cancer in ways that we didn’t know about before,” said Firpo.

Experimental treatment eradicates acute leukemia

A diverse team of scientists from University of California, Los Angeles (UCLA), Jonsson Comprehensive Cancer Center, the United States, have developed an experimental treatment that eradicates an acute type of leukemia in mice without any detectable toxic side effects. The drug works by blocking two important metabolic pathways that the leukemia cells need to grow and spread. The study, led by Dr. Caius Radu, associate professor and Dr. David Nathanson, assistant professor, was published in the journal Experimental Medicine.

Metabolism is the inner workings of cells, and the many mechanisms and chemical reactions that maintain the cell and allow it to survive and reproduce by division. Elements of metabolism called biosynthetic pathways allow cells to synthesize chemicals, called nucleotides, that they need to survive. When these nucleotide pathways are blocked by drug molecules, cancer cell growth can be halted and cell death can be triggered. Researchers found that an important nucleotide called deoxycytidine triphosphate (dCTP) is produced by two pathways, the de novo pathway (DNP) and the nucleoside salvage pathway (NSP). When an existing drug was given that blocks the DNP in a leukemia cell, the dCTP nucleotide was still produced by the NSP and the leukemia cell survived.

To counter this switch to the alternative pathway, the researchers created a small-molecule drug called DI-39, which blocks the NSP. When both these drugs are given, both pathways are blocked with a one-two punch, the leukemia cells cannot produce dCTP nucleotides, and the cells die. In this study, the two-pronged experimental treatment was given to mice that had acute lymphoblastic leukemia (ALL, a deadly blood cancer). The treatment eradicated the cancer cells, leaving healthy blood cells alone, and the mice suffered no detectable side effects. “With this study we show that everything can be done in the academic environment. We started this project from scratch and with the help of UCLA scientists from many different disciplines, we have taken the drug through all the steps, nearly ready for clinical trials,” said Radu.

Engineered virus effective against breast cancer cells

Scientists from Memorial Sloan- Kettering Cancer Center (MSKCC), the United States, have discovered a potential cure for one of the most aggressive and least treatable forms of breast cancer called “triple negative breast cancer.” In laboratory experiments involving human cancer cells, scientists used a virus similar to the one that helped eradicate smallpox to coax cancer cells to produce a protein which makes them susceptible to radioactive iodine. Researchers stress that human clinical trials are necessary before any definitive claims of a cure can be made and treatments can be made available. “We hope that the recent advances in virology, genetic engineering and targeted radiotherapy will soon translate into an entire class of novel oncolytic, virotherapies for the treatment of deadly cancers,” said Yuman Fong, a researcher at MSKCC.

To make this discovery, Fong and colleagues successfully infected and killed TNBC cells using a vaccinia virus. In addition, the researchers were also able to use the virus to cause infected cancer cells produce a cell surface protein called hNIS that normally is used to concentrate iodine in thyroid cells. The hNIS protein, expressed in thyroid cancer, is why most thyroid cancers can be cured or successfully treated with a small dose of radioactive iodine (which kills thyroid cancer cells expressing hNIS). Armed with the ability to force TNBC cells to produce this protein, researchers can now deliver anticancer therapies to this deadly and resistant form of cancer.

Researchers open door to new HIV therapy

People infected with the Human Immunodeficiency Virus (HIV) can stave off the symptoms of AIDS, thanks to drug cocktails that mainly target three enzymes produced by the virus, but resistant strains pop up periodically that threaten to thwart these drug combos. However, researchers at the University of California (UC) and the National Institutes of Health (NIH), the United States, have instead focused on a fourth protein, Nef, that hijacks host proteins and is essential to HIV’s lethality. They have captured a high-resolution snapshot of Nef bound with a main host protein, and discovered a portion of the host protein that will make a promising target for the next-generation of anti-HIV drugs. By blocking the part of a key host protein to which Nef binds, it may be possible to slow or stop HIV.

“We have imaged the molecular details for the first time. Having these details in hand puts us in striking distance of designing drugs to block the binding site and, in doing so, block HIV infectivity.” said James H. Hurley, a professor at UC. The report comes a month after President Barack Obama pledged to redirect $100 million in the NIH budget to accelerate development of a cure for AIDS, though therapies to halt the symptoms of AIDS will remain necessary for the immediate future. For many patients, current drug therapies have transformed HIV infection into a chronic condition that doesn’t lead to AIDS, but anything we can develop to further interfere with replication and propagation of the virus would help keep it in check until we find a way to completely eliminate the virus from the body.

Whatever the reason, the virus prevents further HIV infection by ridding the cell surface of all other CD4 receptors. Nef achieves this by tagging the CD4 receptor so that the cell thinks it is trash and carries it to the cell’s incinerator, the lysosome, where it is destroyed. Six years ago, researchers found that Nef does this by directly binding to a host protein, AP2, that latches onto a protein called clathrin. This causes the cell membrane to bulge inward and pinch off to form a small membrane bubble that carries attached CD4 receptors to the lysosome for destruction. The new high-resolution image reveals a cavity at the site where Nef binds to AP2, that could be a good site for drug targeting. “This work was an extension of our work on clathrin adaptors, an opportunity to do something relevant to fighting HIV that was based on the purely basic research we are doing on the sorting of proteins to lysosomes,” Hurley said.


New discovery to stimulate plant growth

Scientists at Durham University, the United Kingdom, have discovered a natural mechanism in plants that could stimulate their growth even under stress and potentially lead to better crop yields. Plants naturally slow their growth or even stop growing altogether in response to adverse conditions, such as water shortage or high salt content in soil, in order to save energy. They do this by making proteins that repress the growth of the plant. This process is reversed when plants produce a hormone – called Gibberellin – which breaks down the proteins that repress growth. Growth repression can be problematic for farmers as crops that suffer from restricted growth produce smaller yields.

The researchers have discovered that plants have the natural ability to regulate their growth independently of Gibberellin, particularly during times of environmental stress. They found that plants produce a modifier protein, called SUMO that interacts with the growth repressing proteins and believe that by modifying the interaction between the modifier protein and the repressor proteins they can remove the brakes from plant growth, leading to higher yields, even when plants are experiencing stress.

The research was carried out on Thale Cress, a model for plant research that occurs naturally throughout most of Europe and Central Asia, but the mechanism scientists have found also exists in crops such as barley, corn, rice and wheat. Dr. Ari Sadanandom, Associate Director said, “The finding could be an important aid in crop production. What we have found is a molecular mechanism in plants which stabilises the levels of specific proteins that restrict growth in changing environmental conditions. If we can encourage the crops to keep growing, even when faced by adverse conditions, it could give us greater yields and lead to sustainable intensification of food production that we must achieve to meet the demands on the planet’s finite resources.”

A genetically modified stress tolerant

A team of researchers led by Lam-Son Tran and colleagues at the RIKEN Center for Sustainable Resource Science (CSRS), Japan, has identified a previously unknown signaling pathway that plays a key role in stress tolerance. The newly discovered signaling pathway is based on the hormone strigolactone. The synthesis of strigolactone, and the plant’s response to its presence, is controlled by a gene family known as More Axillary Growth (MAX), defects in which can lower concentrations of the hormone or impair plant responses to it. Researchers found that Arabidopsis plants with defective MAX genes were much less resilient to drought and high salinity than wild-type plants. Application of artificial strigolactone, however, restored the resistance of low-strigolactone mutants to drought stress and even improved drought resistance in wild-type plants.

By examining gene expression in max mutants, the researchers uncovered multiple genetic targets of the strigolactone pathway. The expression of many of these genes was already known to be induced by drought or hormones such as abscisic acid, suggesting that plants integrate multiple hormonal pathways to provide complex and finely tuned responses to stress. One way that strigolactone acts is by regulating plant transpiration rates. Under drought conditions, max mutants lose water faster than wild-type plants. The gene expression results, however, also suggested a second mechanism of strigolactone action. Photosynthesis-related genes are upregulated in max mutants, implying that normal strigolactone signaling might suppress photosynthesis under environmental stress, reducing demands on the plant’s resources.

The research provides a basis for developing genetically modified drought- or salt-tolerant crops by manipulating genes in the strigolactone synthesis and response pathway. “Stress-inducible promoters could switch on the strigolactone pathway when plants encounter stress,” said Tran. “Thus, under normal growing conditions, the plants could grow without any yield penalty.” There is an intriguing further possibility for growing crops under tough conditions. The application of artificial strigolactone, although expensive to manufacture at present, could be used to increase tolerance to drought stress as an alternative to developing drought-resistant transgenic crops. Contact: RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351- 0198, Japan. Fax: +81-48-462-4715; E-mail:

Scientists identify missing link in plant immunity

Scientists at The Sainsbury Laboratory (TSL), the United Kingdom, have uncovered how an enzyme critical to plants’ rapid immune response against microbes is activated. “The insights will open up new ways to improve disease resistance and stress tolerance in plants,” said Professor Cyril Zipfel. The enzyme, triggers a rapid generation of signalling molecules derived from oxygen that are believed to be detrimental to microbial growth. The newly-discovered way this enzyme is activated, by a protein (called BIK1) fills a gap in how plants perceive a threat and how signals are activated to trigger an immune response.

The work published in the journal Molecular Cell, was conducted by scientists from TSL and from RIKEN, Japan, whose focus on the interactions between plants and microbes can spark innovation in tackling the world’s most important crop diseases. “Understanding how this enzyme was rapidly activated was an important missing link in our knowledge of plant immunity,” said Professor Zipfel. The scientists revealed that the enzyme is regulated by processes some of which are dependent on calcium and some of which are independent of it. “Our findings lay the ground for future research investigating how these processes interact and how they switch on and off the molecules essential to defence and stress responses.”

Researchers unlocked ‘Elite wheat’ secrets

Researchers at the University of Southern Queensland (USQ), Australia, supported by the Grains Research and Development Corporation (GRDC), Australia, have been trawling through the chromosomes of several wheat lines that show resistance to the fungal disease. They hope they have finally unlocked their secret, identifying between three and five genetic regions in each line that work together to create resistance. These key genetic regions are now being incorporated by commercial breeding companies into the DNA of high-yielding varieties to create adapted, high-yielding wheats, which will reduce losses due to the disease.

Professor Mark Sutherland, said that the research is at an exciting stage, with the most recent field trials showing promising early results. He was hopeful the first of the adapted wheat germplasm could be available to commercial wheat breeding companies in three years to be used in commercial variety development, although he stressed that the research was still a long way from complete and results were not yet guaranteed. “We are as confident as you can be when you are dealing with the difficult genetic systems present in wheat that we are on the right track,” Professor Sutherland said.

A novel battleground for plant-pathogen interactions

Scientists at The Sainsbury Laboratory (TSL), in collaboration with Michigan State University (MSU) and the University of Illinois (UIC), the United States, have unveiled a new way in which plants perceive pathogens to activate immunity. They also revealed how pathogens inhibit the mechanism to cause disease. It was previously only associated with other pro-cesses in mammalian cells. When plants detect microbial molecules, they trigger immune responses to prevent disease. Although several plant immune receptors for these microbial molecules are known, how they are activated once the microbe is recognised is not well understood.

In a study published in the journal Science, the scientists found that phosphorylation of an amino acid called tyrosine – phosphorylation being a process that can turn molecules on or off – is key for activating plant immune receptors. This mechanism is already known to play an essential role in the activation of mammalian receptors, and its mis-regulation is often linked to important chronic diseases. “This finding opens the door to improving crop disease resistance as we can investigate ways to optimise how plants recognise pathogenic microbes and provides a new link between our un-derstanding of cellular signalling in plant and animal cells,” said Cyril Zipfel, a professor at TSL.

Sugarcane converted to oil-producing crop

A multi-institutional team has reported that it can increase sugarcane’s geographic range, boost its photosynthetic rate by 30 percent and turn it into an oil-producing crop for biodiesel production. These are only the first steps in a bigger initiative that will turn sugarcane and sorghum – two of the most productive crop plants known – into even more productive, oil-generating plants. The team presented its latest findings at the ARPA-E Energy Innovation Summit, the United States, on February 25. “Biodiesel is attractive because, for example, with soybean, once you’ve pressed the oil out it’s fairly easy to convert it to diesel,” said Stephen P. Long, a professor at University of Illinois, the United States.

Using genetic engineering, the researchers increased photosynthetic efficiency in sugarcane and sorghum by 30 percent and to boost cold tolerance, they are crossing sugarcane with Miscanthus, a related perennial grass that can grow as far north as Canada. The new hybrid is more cold-tolerant than sugarcane, but further crosses are needed to restore the other attributes of sugarcane while preserving its cold-tolerance, Long said.


Nanomedicine: Principles and Perspectives (Nanostructure Science and Technology)

Nano-scale science and technology have revolutionized medicine by enabling researchers to gain a deeper un-derstanding of many diseases and offers new insights in fields as diverse as diagnostics, therapy, imaging, drug delivery, and regenerative medicine. Increasing demand and awareness of applications of nanotechnol¬ogy in medicine has resulted in the emergence of a new fast-growing discipline – nanomedicine. This book aims to bridge the gap between nanotechnology and medicine through contributions by world-renowned experts.

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Nanoscience and Nanoengineering: Advances and Applications

This book provides readers with selected recent break¬throughs in six nanotechnology platforms that exhibit high impact potential. These platforms include nano¬electronics, nanobiology, nanomedicine, nanomod¬eling, nanomanufacturing and related applications, and nanosafety. The chapters are designed to convey synergistic advances in understanding and applica¬tion opportunities that can be achieved through an interdisciplinary approach to exploring each platform.

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Structural Genomics and Drug Discovery: Methods and Protocols (Methods in Molecular Biology)

The book focuses on high throughput structure de¬termination methods and how they can be applied to lay the groundwork for structure aided drug discovery. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materi¬als and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls.

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