VATIS Update Biotechnology . Jan-Mar 2012

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Biotechnology Jan-Mar 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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Global seed treatment market on fast growth mode

In the global crop protection market, seed treatment is the fastest growing segment, says Seed Treatment Market Trends and Global Forecasts (2011-2016) a market research report published recently by MarketsandMarkets. Government encouragement for adoption of seed treatment as crop protection practice is fuelling this growth, which is particularly high in geographies such as Latin America and Asia-Pacific due to increased acceptance of genetically modified (GM) seeds and farmers’ awareness of maximum residue levels.

The global seed treatment market exceeded US$2.25 billion by the end of 2010, and is expected to grow to US$3.43 billion by 2016, at a compound annual growth rate (CAGR) of 13.5 per cent from 2011 to 2016. The North American market is expected to hold 22 per cent of the global market share by 2016, at an estimated CAGR of 16.4 per cent due to higher acceptance of GM seeds for soybean and maize. Asia-Pacific is another area that is growing fast due to the constant push by government agencies for adoption of seed treatments. The region’s market share is expected to boost from US$157.5 million in 2010 to US$248.2 million by 2016, at an estimated CAGR of 14.4 per cent (2011 to 2016).

Seed treatment chemicals – which include seed treatment insecticides and fungicides – were biggest market segment in 2010, owing to their widespread use in bulk quantities. Chemical seed treatments currently control over 98 per cent of global seed treatment market, while bio-control seed treatments are expected to grow at a faster pace than any other segment because of the push by governments to reduce agrochemicals usage.

Transparent biotech regulatory system in the works in India

To make sensible use of the biotechnological tools and techniques for the benefit of the people, the Ministry of Science & Technology of India will soon set up a transparent and evidence-based regulatory system, said Science & Technology (S&T) Minister, Mr. Vilasrao Deshmukh, at the 99th session of Indian Science Congress at Bhubaneswar on 3 January 2011. The Ministry is also working on a fresh S&T policy. Speaking at the Congress, Mr. Deshmukh said, “We need a new and well enunciated science, technology and innovation policy. It should promote an innovation ecosystem that addresses the national priority for inclusive and sustained growth.”

Talking about the inadequate R&D spending, Mr. Deshmukh said, “Investments in research and development (R&D) will be increased from present level of less than one per cent to two per cent of the GDP.” The Minister also called for a paradigm shift, saying: “Current Indian policies treat the R&D sector in segregated compartments. A change in the policy paradigm for treating the entire R&D sector in the country as one and developing public-private partnerships for R&D to promote public and social good are important new strategies. R&D outputs should be converted into measurable economic and social outcomes.”

The Minister said that the nation need big ideas in science, new methods in governance of R&D systems, right resources investment, aspiration to emerge as a world leader in science, and dedication to serve the people of India through technology and affordable innovations, adding that he hoped that India would emerge as a key player in the science world before the end of 2017.

First cell-based flu vaccine plant in the United States

The first United States facility to employ a faster and more flexible technology to make influenza vaccine was dedicated recently to the nation, as part of an initiative that could provide vaccine supplies sooner in an influenza pandemic. The plant in Holly Springs, North Carolina, can create vaccine using cultured animal cells instead of the conventional process of using fertilized eggs. It is a public-private partnership of the United States Department of Health and Human Services (HHS) and Novartis Vaccines and Diagnostics Inc., and contract will be maintained for at least 25 years.

The dedication signals that in an influenza pandemic the facility can produce cell-based influenza vaccine that could be authorized by the United States Food and Drug Administration (FDA) for use during the emergency. The new facility may be able to produce 25 per cent of the vaccine needed in the United States. The cell-based technology employed in this facility for manufacturing influenza vaccines may be adapted to produce vaccines for other emerging infectious diseases in an emergency.

In addition to partnering to bring cell-based flu vaccine and adjuvant technologies to the United States, HHS and Novartis are partnering with Synthetic Genomics Vaccines on new technologies to shorten the vaccine manufacturing timeline by optimizing the vaccine virus seed strains used for production.

Making a bid to be a life science hub

With an aspiration to get a global recognition as a life science hub in Asia, the Taiwan Province of China is gearing up to boost its start-up ventures. In the past few months, the province has taken some strategic steps that have the potential to position it among the lucrative markets of Asia, therefore drawing Asian and global attention for investments, clinical trials and joint research projects. It recently set up the Supra Incubation Centre (SIC) with the objective of integrating various resources to accelerate the growth of biotechnology companies. SIC is designed to identify new and profitable drugs and equipment that have potential value for future and facilitate to bring them to the market in a short time. With this initiative, a biotechnology venture capital fund of over US$330 million has been raised from private and public sectors. According to the Council for Economic Planning and Development, the government had allocated a budget of US$1.27 billion for the establishment of SIC, relaxed rules for the establishment of biotech venture funds and recruited talent from overseas.

The government has decided to pump in money from the national development fund, and this is expected to stimulate the establishment of more biotech venture capital funds to channel domestic and foreign capital into the province’s biotech industry. According to the Biotechnology and Pharmaceutical Industries Programme Office, the total revenue from medical devices industry in the province was US$2.59 billion in 2009. Industrial Technology Research Institute’s Rapid Prototyping Centre pursues time efficiency as the top priority. Centralized around quality management system, it is expected that processes starting from design, development and prototyping to various testing can be completed at the Centre in 6-9 months.

These initiatives and investments by the government are expected to also create job opportunities for Asian talents who have adequate experience in related fields, and attract its human resources back to the province. However, there are certain challenges that the province has to overcome to optimally utilize its resources. For instance, out of the 100 hospitals that are involved in clinical studies, only the top 20 are prominent enough to attract global clinical trials. In addition, most companies in this sector are of small and medium size, and are in the technology or product development stage. The industry would therefore need to develop strategic alliances with international biotech companies.

Ireland invites venture capital firms

The Government of Ireland recently announced an investment of US$ 37.5 million in a United States life sciences fund that invests in biotechnology with focus on the development of sophisticated drugs. It also plans to invest 60 million euros in venture capital (VC) funds that establish a presence in the country. While it was “a global call”, the target is the United States at a time when biotechnology is under pressure. At the same time, there is a fear that United States VC companies being effectively paid to open offices in Dublin would likely increase the likelihood of exits for the companies through early sell-offs, rather than helping to develop a significant indigenous biotech base in Ireland. The government’s science policy as the total public science budget in a decade has cost 20 billion euros and the odd spin-out from tertiary research invariably gets acquired by a bigger United States firm.

EMA to refine biosimilar rules

The European Medicines Agency (EMA), located in London, has proposed revising guidelines for biosimilar products. In mid-November the Agency said that the current “conceptual” guidelines – which date back to 2005, when no bio­similar products were marketed in the EU – no longer seem appropriate in light of the experiences it has now had with a large number of marketing authorization applications (MAAs) and consultations with applicants. In a paper due to be released by February 2012, the Agency states that:
  • The principles of biosimilarity may have to be explained more clearly;
  • The term “biosimilar” has been used in an inappropriate way;
  • Discussion is needed on feasibility for following a generic legal basis for some biological products; and
  • Certain aspects need to be discussed for potential refinement.

EMA states that the current focus of biosimilar development programmes is to establish similarity to the reference product, not clinical benefit. Consequently, an update of the guideline should make this principle – and its consequences – clearer to the reader. Therefore, EMA proposes a discussion on the equivalence of efficacy and safety aspects, if not covered by the revision of the general non-clinical and clinical guidelines.

According to the 2005 guidelines, a substance’s pharmaceutical form, strength and route of administration should be the same for the biosimilar and the reference medicinal product. But now the Agency says that talks must take place on whether providing additional data in case of non-comparability is realistic. Finally, the current guideline provides a long list of references, including antiquated ones. EMA wants to discuss whether these references should also be updated, as many more biosimilar-related guidelines have been drafted since 2005.

Draft guidance on biosimilar product development

The United States Food and Drug Administration (FDA) has issued three draft guidance documents on biosimilar product development “to help the industry develop biosimilar versions of currently approved biological products, which can enhance competition and may lead to better patient access and lower cost to consumers,” said Dr. Janet Woodcock, Director, FDA Centre for Drug Evaluation and Research.

The Patient Protection and Affordable Care Act that became law in March 2010, amended the Public Health Service Act to create an abbreviated approval pathway for biological products that are shown to be biosimilar to or interchangeable with an FDA-licensed biological product. This pathway allows biological products to be approved based on demonstrating they are biosimilar to, or are interchangeable with, a biological product that is already approved by FDA, which is called a reference product.

The guidance documents issued are: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product; and Biosimilars – Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009. These three documents provide FDA’s current thinking on key scientific and regulatory factors involved in applying for biosimilar products to the agency. FDA is seeking public comment on these draft guidance documents.

Indian nutraceutical market set for substantial growth

The nutraceutical market in India is expected to grow at a compound annual growth rate (CAGR) of 13 per cent to US$2,731 million in 2016. Functional foods will be the quickest growing category till 2015 followed by dietary supplements. Dietary supplements, particularly herbal and dietetic supplements, will form the greatest opportunity areas for nutraceutical manufacturers, driven by growing demand from an evolving consumer base, states a report titled The Indian Nutraceutical Market: Dynamics of a Consumer Driven Market from Frost & Sullivan.

Pharmaceutical and fast-moving consumer goods (FMCG) giants dominate the Indian nutraceutical market. While dietary supplements such as vitamins and mineral supplements have been captured by pharma companies, functional food and beverages are being brought to the market by FMCG companies. However, certain segments like dietetic supplements are now being catered to by pure nutraceutical companies, apart from their pharmaceutical and FMCG counterparts. According to the report, the Indian nutraceutical market was worth US$1,480 million in 2011, with dietary supplements accounting for 64 per cent of the market.

The global nutraceutical market in 2011 was estimated to be US$ 149.5 billion, with the United States, Europe and Japan being the largest regional markets accounting for nearly 93 per cent of the global nutraceutical demand. These markets are nearing maturing, with exceedingly high per capita spends on nutraceuticals products. Nutraceutical manufacturers are thus forced to look at developing countries, such as India and China, which have considerably lower per capita spends on nutraceutical products, as key growth regions for their nutraceuticals portfolio.


GSK, Angiochem to work on lysosomal storage diseases

GlaxoSmithKline (GSK), based in the United Kingdom, and Angiochem, Canada, have inked a global collaboration focused on the development and commercialization of treatments for lysosomal storage diseases (LSDs). The partnership will combine GSK’s expertise in rare diseases with Angiochem’s capabilities in the development of compounds that can cross the blood-brain barrier. The ultimate aim is to develop engineered peptide compound (EPiC) drugs, which can restore enzyme function in the central nervous system (CNS), and thus address neurological symptoms associated with LSDs.

The partnership will initially focus on the creation and development of an enzyme replacement therapy for a specified LSD. GSK will be able to assume all development and commercialization rights to the product. Other LSD targets may subsequently be included in the scope of the agreement. Angiochem could receive over US$300 million from GSK, including up to US$31.5 million in up-front cash, research funding and other fees, if GSK accesses the LSD targets available to the partnership.

Lupin plans to invest in Indian plant

Lupin Pharmaceuticals, based in the United States, plans to spend over Rs 2.3 billion (US$43.69 million) in capital expenditure for its Indian manufacturing plants during 2011-2012, a top company official said. The company spent about Rs 1.29 billion (US$24.4 million) in capital expenses in the quarter ending 30 September and intends to spend totally Rs 5 billion (US$ 94.98 million) for the year ending 31 March 2012, according to Mr. Ramesh Swaminathan, Lupin’s President for Finance & Planning.

Net sales of Lupin grew by 24 per cent to Rs 17.4 billion (US$330.5 million) during the third quarter of 2011, up from Rs 14.1 billion (US$ 267.8 million) in the same period of 2010. Net profits grew by 24 per cent to about Rs 2.7 billion (US$ 51.3 million) as compared with approximately Rs 2.2 billion (US$41.8 million) in the same period in 2010.

Protagen expands cooperation with Bayer HealthCare

In Germany, Protagen AG, an in-vitro diagnostics specialist, and Bayer HealthCare Pharmaceuticals, a global specialty pharmaceuticals company, have started a collaboration project for the clinical validation of diagnostic biomarkers in endometriosis. This new project builds on the results of the endometriosis biomarker discovery study conducted in 2011, and is already the third UNIarray® Project within the collaboration between the two companies in the last three years. The aim of the current study is to employ UNIarray technology for the predictive diagnosis of Endometriosis to help improve a patient’s quality of life. New technologies like UNIarray are becoming increasingly important to understand the biochemical and biomolecular processes of endometriosis.

“Now we can directly support our collaboration partners in pharma and biotech in all clinical Phases I-IV with the development of therapy specific diagnostic assays,” states Dr. Peter Schulz-Knappe, Chief Scientific Officer and Executive Vice President Diagnostics at Protagen. Besides endometriosis, UNIarray technology is applied in autoimmune diseases like multiple sclerosis, chronic inflammatory diseases and cancer.

Jubilant secures multi-million dollar contract

Jubilant Life Sciences subsidiary Jubilant HollisterStier, the United States, has recently secured contracts with four innovator life science companies for the commercial manufacturing of sterile parenteral products for the United States and Europe. These agreements cover contract manufacture of products ranging from liquid to lyophilization presentations, across a variety of patient indications, for a total value of over US$90 million to be delivered over a five-year period. Mr. Shyam S. Bhartia and Mr. Hari S. Bhartia, Chairmen & Managing Directors of Jubilant Life Sciences said, “We are pleased with signing of these long-term contracts with innovator pharma companies to serve the regulated markets of the United States and Europe.”

Samsung and Biogen Idec in biosimilar joint venture

Samsung Biologics, the Republic of Korea, and Biogen Idec Inc., the United States, have established a US$300 million joint venture to develop and market biosimilars. The initiative, located in the Republic of Korea, will be led by Samsung, which will contribute US$225 million for an 85 per cent stake. The venture will contract mainly with Biogen Idec and Samsung Biologics for technical development and manufacturing services. However, it will not look to develop biosimilars of Biogen Idec’s products.

Samsung Biologics was set up in April 2011 to specialize in biopharmaceutical manufacturing. “This relationship will allow us to leverage our world-class protein engineering and biologics manufacturing capabilities, while maintaining focus on our mission of discovering, developing, and delivering innovative therapies for patients worldwide with neurodegenerative diseases, haemophilia and autoimmune disorders,” commented Mr. George A. Scangos, CEO of Biogen Idec.

India’s first bio-absorbable stent venture launched

In India, a group of alumni of the Indian School of Business (ISB) are investing around Rs 1.3 billion (US$24.7 million) in their new company to produce the country’s first bio-absorbable stent, which would dissolve itself after treating blockages in the heart. S3V Vascular Technologies, which was started by four former ISB students, has already kicked off animal trials of this bio-absorbable endovascular drug-coated stent, called ‘Avatar’. The company also aims to produce catheters, disposables and other devices used in angiographic procedures in radiology and cardiology. India currently imports these devices at very high costs, making critical life-saving treatments very expensive.

The pilot plant for producing these devices will be ready by April 2012. The overall interventional cardiology products market in India is expected to grow from around US$ 249.3 million in 2008 to an estimated US$635.7 million in 2012. S3V Vascular Technologies also hopes to form joint ventures to spin off its technology and gain access to other specialty areas.

Novartis invests US$600 million in R&D complex

Novartis’ scientists in Boston, the United States, appear to be getting pampered in the company’s planned US$600 million research and development (R&D) complex in Cambridge, Massachusetts, where several ace designers have been assembled for the project, according to a report in The Boston Globe. While the Swiss drug giant is laying off R&D personnel elsewhere, site work has already begun for the R&D complex expected to add to the company’s already sizable research base in the backyard of Massachusetts Institute of Technology (MIT).

To complement Novartis’ desire for its scientists from different disciplines to mingle – in order to join forces on breakthrough drugs – the complex will feature meeting areas, courtyards and close proximity to the company’s existing R&D and office buildings, according to the article.

The project exemplifies the growing focus of biopharmaceutical outfits on the Boston area, which enjoys a world-class cluster of top academic centres, research hospitals and innovative companies. Drugmakers want ample access to this cluster to score talent and science to lead the way to future medicines. While Novartis’ global R&D base in Cambridge gets a shiny new campus, however, the company is scaling back other operations in the United States and Switzerland.

Sanofi gets global rights on treatment for bone disorders

Sanofi S.A., France, has exclusively licensed from Scil Technology GmbH, Germany, the latter’s programme for regenerative treatment of osteoarthritis and cartilage disorders. Under the agreement, Scil Technology will receive an upfront payment and potential milestone payments totalling up to 180 million euros. The company will also receive undisclosed royalties on worldwide product sales. Sanofi will assume responsibility for the progression of the development programme with immediate effect, including the start of clinical trials. The Scil programme is currently in advanced preclinical development.

“Osteoarthritis is a painful and disabling disease that affects millions of patients. At present, there is no available therapy that has been proven to impact the progressive joint damage that is associated with the disease,” stated Mr. John Alam, Head of Therapeutic Strategic Unit – Aging, Global Research and Development, Sanofi. “Scil Technology’s cartilage regenerative program brings an innovative approach to Sanofi’s osteoarthritis portfolio that we believe may have promise to address progressive joint damage by targeting the activation of body’s internal mechanism of cartilage repair and regeneration.” The cartilage regenerative programme is Scil Technology’s second programme that has been out-licensed successfully.
Source: http:/


Genome of pigeon pea cracked

Pigeon pea (Cajanus cajan) is set to join the world’s league of major food crops with the completion of its genome sequence. The genome study by a global research partnership – led by the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) based in India – provides an overview of the structure and function of the genes that define what makes a pigeon pea plant. It also reveals valuable clues on how the genomic sequence could be useful to crop improvement for sustainable food production.

Of the 48,680 pigeon pea genes identified, couple of hundred were found unique to the crop in terms of drought tolerance, an important trait that could be transferred to other similar legume crops like soybean, cowpea or common bean that belong to the same family. Pigeon pea – grown on about 5 million hectares in Asia, sub-Saharan Africa and South-Central America – is a very important food legume for millions of the poor in the semi-arid regions of the world, since it provides a well-balanced diet when accompanied with cereals.

Pigeon pea is the second food legume (after soybean) and the first non-industrial crop with a completed genome sequence. An improved understanding of the pigeon pea genome will have a major impact on improved crop productivity, tackling pests and disease constraints in production, and improved resistance to harsh environments and variable climate.

Genetic finding to help develop cheaper biofuels

Researchers at Joint BioEnergy Institute (JBEI) of the United States Department of Energy (DOE) have announced a major breakthrough in engineering systems of RNA molecules via computer-assisted design. Scientists will use these new “RNA machines” to adjust genetic expression in the cells of micro-organisms. This will enable scientists to develop new strains of Escherichia coli that are better able to digest switchgrass biomass and convert released sugars to form three types of transportation fuels – petrol, diesel and jet fuels.

The scientists specifically focused the design-driven approach on RNA sequences that can fold into complicated 3-D shapes, called ribozymes and aptazymes. Using JBEI-developed computer-aided models and simulations, the researchers then created complex RNA-based control systems that are able to program a large number of genes. In micro-organisms, commands that are sent into the cell will be processed by the RNA-based control systems, enabling them to help develop desired products.

3-D mapping of human genome

Dr. Yijun Ruan, Associate Director of Genomic Technologies at Genome Institute of Singapore (GIS), led a continuing study on human genome spatial/structural configuration, showing how genes interact/communicate and influence each other, even when they are located far away from each other. This discovery is crucial in understanding how human genes work together. Using ChIA-PET, a genomic technology invented by Dr. Ruan and his team, the international research group uncovered some of the fundamental mechanisms that regulate gene expression in human cells.

The findings in this study revealed that although human genes are located far away from each other, related genes are in fact organized through long-range chromatin interactions and higher-order chromosomal conformations. Dr. Edward Rubin, Director of the Joint Genome Institute, the United States, says that Dr. Ruan and his team have addressed the basic question of how communication occurs between genes and their on and off switches in the human genome. The study reveals in 3-D space that “genes separated linearly by enormous distances in the human genome can come to lie next to each other in the cell when it is time for them to become active,” he states.

A genetic hope for global food security

In the United Kingdom, scientists have discovered a ‘nourishing gene’ that controls the transfer of nutrients from plant to seed – a significant step that could help increase global food production. The study led by the University of Warwick, in collaboration with the University of Oxford and agricultural biotech research company Biogemma, has identified Meg1, a gene that optimizes amount of nutrients flowing from mother to offspring in maize.

Unlike the majority of genes that are expressed from both maternal and paternal chromosomes, Meg1 is expressed only from the maternal chromosomes – an unusual form of uniparental gene expression called imprinting. Scientists have known for a while of the existence of such imprinted genes in humans and other mammals, but this is the first time a parallel gene to regulate nutrient provisioning during seed development has been identified in the plant world. The findings mean that scientists can now focus on using the gene and understanding the mechanism by which it is expressed to increase seed size and productivity in major crop plants.

Dr. Jose Gutierrez-Marcos, Associate Professor in the University of Warwick’s School of Life Sciences, said: “This understanding of how maize seeds and other cereal grains develop – for example, in rice and wheat – is vital as the global population relies on these staple products for sustenance.” Professor Hugh Dickinson of Oxford University’s Department of Plant Sciences added: “While the identification of Meg1 is an important discovery in its own right, it also represents a real breakthrough in unravelling the complex gene pathways that regulate the provisioning and nutritional content of seeds.”

Does longevity gene raise dementia risk?

A recent study of a group of 540 long-living Ashkenazi Jews by researchers at the Albert Einstein College of Medicine in Bronx, the United States, pointed to several genes that might help explain the secret of longevity. One gene, in particular, stood out. The oldest of the old who bear a certain version of the cholesteryl ester transfer protein gene (CETP I405V) end up with lower levels of CETP protein but higher levels and larger particles of high-density lipoproteins (HDLs), the “good” cholesterol. The carriers of two copies of this gene variant – one from the mother and another from the father – appear to have a lower risk of dementia, failing memories and heart disease.

However, a subsequent study by researchers from Rush University Medical Centre, the United States, identified the CETP variant as a gene that may increase the risk of Alzheimer’s disease. The same version of the same gene: in one study it slows dementia, while in the other it promotes cognitive decline. Two groups of well-regarded researchers come to the exact opposite conclusions, in the wild-and-woolly world of gene-association studies that attempt to tie DNA to disease.

The researchers at Rush had decided to investigate the gene variant after reading a study published by the Einstein investigators. The article found that the CETP variant protected a diverse group of older people, aged 70 and older, against failing memory and dementia. The Rush team decided to see whether they could replicate the findings of the Einstein study. Their analysis of 1,384 participants from the two studies found that the CETP variant was associated with a faster rate of cognitive decline and an increased risk of Alzheimer’s. They then did something that the Einstein team hadn’t. They went to pathology information collected on the brains of 590 of the deceased study participants. The researchers found that those with the relevant CETP variant had a greater density of the plaques characteristic of Alzheimer’s disease than others who did not.

A leader of the Rush team points out the possibility that both results may be due to chance – “They got an effect, they reported it; we got an opposite effect, we reported it,” said Dr. David Bennett, a professor of neurological sciences at Rush and one of the co-authors on the paper. “Maybe the truth is in the middle, which is no effect.”

The first complete sequencing of Mongolian genome

In China, Inner Mongolia Agricultural University (IMAU), Inner Mongolia University for the Nationalities (IMUN) and BGI, the largest genomics organization in the world, have jointly carried out the first complete sequencing of Mongolian genome. This genomic study will help researchers to better understand the evolutionary process and migration of Mongolians and their ancestors from Africa to Asia, and lay an important genomic foundation for further human genetic diseases research.

In this study, the DNA sample was from a male adult who belonged to the Mongolian “Royal Family” and is the 34th generation descendant of Genghis Khan – a very valuable sample with a full record of family pedigree and without background of intermarriage with any other ethnic groups. “We believe that the genomics study of Mongolian will help us to explore the distinctive features of Mongolian and the genetic differences with other ethnic groups, including the medical genetics and incidence of genetic diseases,” stated by Mr. Ye Yin, Director of Research and Cooperation Division at BGI.


Protein structures give disease clues

Using some of the most powerful nuclear magnetic resonance equipment available, researchers at the University of California, Davis, the United States, are making discoveries about the shape and structure of biological molecules – potentially leading to new ways to treat or prevent diseases such as breast cancer and Alzheimer’s disease. These 3-D structures, according to chemistry professor Dr. James Ames, give insight into how they function in the cell.

The researchers described the workings of two protein channels that are similar in structure and function. Inositol triphosphate is the “key” that unlocks the inositol triphosphate receptor, opening a gateway that releases calcium inside the cell. The ryanodine receptor does the same thing when it binds another molecule, ryanodine. The new 3-D view shows that although the sequences of these proteins are different, their structures at the “receptor end” are very similar. “They are basically super-imposable,” Dr. Ames said. They are also interchangeable – if the “receptor end” of one is grafted to the “calcium channel end” of the other, the receptor still functions.

On being activated with the right amount of calcium, one calmodulin protein attaches to two oestrogen receptors and draws them into a bear hug. That structure, a dimer, is sensitive to the oestrogen’s attaching to another part of the molecule. In the right amounts, the combination of oestrogen, calmodulin and calcium allows the oestrogen receptor to attach to DNA and turn particular genes on or off. The structure also reveals how calmodulin stops the oestrogen receptor from being broken down and removed. Another protein, ubiquitin, is responsible for attaching to proteins inside cells and flagging them for disposal. When calmodulin blocks those parts of the oestrogen receptor where ubiquitin can attach, that could result in a build-up of oestrogen receptors – which is associated with tumour formation, Dr. Ames said.

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.

Cell membrane proteins as targets for vaccines

Stimulating specialized immune cells to recognize foreign cell membrane proteins that are common to bacterial species may yield vaccines with broader reach, say researchers at Children’s Hospital of Pittsburgh (CHP) of University of Pittsburgh Medical Centre (UPMC) and the University of Pittsburgh School of Medicine (UPSM), the United States. The approach could be of help in preventing infection by multi-drug resistant organisms.

In humans, the cell-signalling molecule family called interleukin-17 (IL-17) is turned on in a specialized group of immune cells in the T helper-cell lineage, known as Th17 cells, said senior author Dr. Jay K. Kolls, a UPSM professor of paediatrics and immunology, and Director of Richard King Mellon Foundation Institute for Paediatric Research at CHP. “That development led us to think that perhaps Th17 cells confer some immunological advantage for eliminating infectious organisms beyond the antibody strategy that we typically employ when we make vaccines,” he explained.

The research team exposed mice to Klebsiella pneumoniae bacteria, a common cause of lung infection, and re-exposed them many weeks after they recovered from the first pneumonia. They found that the presence of the germ in both instances led to increased numbers of Th17 cells in lungs and spleen. But when they blocked IL-17, the mice still developed immunity to infection. The antibody response, which is controlled by B cells, did not require IL-17 to become established. Next, they infected mice bred to lack B cells, which make antibodies, with the bacteria. They found that the animals could become immunized against repeat infection as long as IL-17 was unblocked, allowing Th17 cells to develop an immunological memory of K. pneumoniae.

How a protein protects cells from HIV infection

In the United States, a novel discovery by researchers at New York University (NYU) Langone Medical Centre and colleagues reveals a mechanism by which the immune system attempts to halt the spread of human immunodeficiency virus (HIV). Harnessing this mechanism may open up new paths for therapeutic research that aims to slow down the progression of HIV to acquired immunodeficiency syndrome (AIDS).

Recent studies have found that immune cells, called dendritic cells, containing the protein SAMHD1 are resistant to infection by HIV. Since the discovery, scientists have tried to understand how SAMHD1 works to protect these cells, with hopes that science might find a way to synthetically apply that protection to other cells. Co-lead investigator Dr. Nathaniel R. Landau, a professor of microbiology at the Joan and Joel Smilow Research Centre at NYU School of Medicine, and his team are now able to provide an answer. When HIV infects a cell, it hijacks the cell’s molecular material to replicate. That molecular material is in the form of deoxynucleotide triphosphates (dNTPs), the building blocks for DNA. Once the virus replicates, the resulting DNA molecule will contain all the genes of the virus and instruct the cell to make more virus.

Researchers found that SAMHD1 protects the cell from viruses by destroying the pool of dNTPs and leaving the virus without any building blocks to make its genetic information – a process researchers call nucleotide pool depletion. As a result, the most common form of HIV does not readily infect these cells. Instead, the virus has now evolved to replicate in a different kind of cell, called CD4 T-cells, which do not contain SAMHD1 and therefore have a healthy pool of dNTPs. Dr. Landau explained that the virus has evolved in such a way that it may deliberately avoid trying to infect immune cells with SAMHD1 to avoid alerting the immune system to activate a variety of antiviral mechanisms to attack the virus. Viruses that are related to HIV, like HIV-2 and SIV, have developed a protein called viral protein X (VPX) that directly attacks SAMHD1. This allows the virus to infect dendritic cells, an important type of immune cell.

New method to observe proteins fold

A team of chemists at the University of Pennsylvania, the United States, has devised a way to observe proteins fold in “real-time”, which could lead to a better understanding of protein folding and misfolding. The research led by Dr. Feng Gai, a chemistry professor in the School of Arts and Sciences, used used two lasers to oberve structural changes as a function of time of a model protein known as Trp-cage. The first laser acted as the starting gun; by heating the molecule, it caused its structure to change. The second laser acted as the camera, following the motions of the protein’s constituent amino acids.

Even in a simple protein like Trp-cage, there are several identical bonds, and the researchers need to be able to distinguish one from another in order to see which of them are moving while the protein folds. One strategy they used to get around this problem was to employ the molecular equivalent of a tracking device, an amino acid with a carbon isotope marker, to infer the position of the atoms as they fold. The scientists then tuned the frequency of the laser to match different parts of Trp-cage, allowing them to isolate the parts for analyses. Similar isotopes could be inserted in more complex molecules to view folding.


New technology to tap potential new antibiotics

Scientists at Rockefeller University, the United States, have reported a new technology for sifting through the world’s largest remaining pool of potential antibiotics to discover two new antibiotics that are effective against deadly drug-resistant microbes, including the “super bug” or methicillin-resistant Staphylococcus aureus (MRSA). The scientists – from Laboratory of Genetically Encoded Small Molecules, Genomics Resource Centre and Howard Hughes Medical Institute – explain that an urgent need exists for new medications to cope with micro-organisms that shrug off the most powerful traditional antibiotics.

The typical way of discovering new antibiotics involves identifying and growing new bacteria from soil and other environmental samples in culture dishes in the laboratory. Researchers then analyse the bacteria to see if they make substances that are useful as antibiotics to kill other microbes. However, as most bacteria found in nature can’t grow in the laboratory, Rockefeller scientists took a new approach. They removed DNA from soil bacteria that wouldn’t grow in the lab and put this DNA into different bacteria that do grow well in culture dishes. These bacteria acted like incubators for the new DNA.

The “metagenomics” method enabled the research team to study the substances made by the soil bacteria’s DNA in the lab. They identified two new possible antibiotics called fasamycin A and fasamycin B that kill MRSA and vancomycin-resistant Enterococcus faecalis, which also is becoming more resistant to known antibiotics.

New microfluidic device for cancer diagnosis

Separating complex mixtures of cells, such as those found in a blood sample, can offer valuable information for diagnosing and treating disease. However, to do so, one may need to search through billions of other cells. Researchers at Massachusetts Institute of Technology (MIT) and Massachusetts General Hospital (MGH), the United States, have demonstrated a new microfluidic device that can isolate target cells – such as tumour cells, stem cells or foetal cells – much faster than existing devices. Such technology could be used in applications such as point-of-care diagnostics and personalized medicine.

Researchers have used a number of techniques to sort cells based on differences in size, density or electrical properties. However, as the physical characteristics of cells can and do vary significantly, these techniques risk separating cells incorrectly, leading to an erroneous diagnosis. A more specific way to isolate cells is to use antibodies that latch on to distinctive molecules displayed on the surfaces of the target cells. In order to achieve that, the MIT and MGH researchers designed a device to guide the fluid towards the bottom of the channel as it flows, bringing more of the cells in contact with the antibodies. A salient aspect of the new design is the use of a soft membrane, which is bestowed with nanoscale pores, to separate two adjacent microchannels.

Cells enter one channel only, and as they flow through the channel, the fluid is rapidly drawn to the porous divider, bringing the cells with it. Fluid can pass into the other channel, but the cells cannot. Once they reach the surface, they start rolling – slowly enough that target cells have the time to attach to the antibodies and get captured, but fast enough to keep the other cells moving. Such rolling behaviour is similar to how white blood cells or stem cells selectively home in to sites of infection and injury in the body. One potential application for the device is to isolate cancer cells from patient blood samples.

HIV/AIDS vaccine bestows long-term protection

In the United States, a research collaboration between Emory University and GeoVax Labs Inc. may be a step closer to finding a vaccine that will provide long-lasting protection against repeated exposures to human immunodeficiency virus (HIV). The vaccine developed by scientists – led by Dr. Harriet L. Robinson, GeoVax’s Chief Scientific Officer, and Dr. Rama Rao Amara, an Associate Professor at Yerkes National Primate Research Centre and Emory Vaccine Centre – has protected non-human primates against multiple exposures to simian immunodeficiency virus (SIV) given in three clusters over more than three years.

The vaccine regimen included a DNA prime vaccine that co-expressed HIV proteins and granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a normal protein that promotes the initiation of immune responses and thus enhances the ability of the vaccine to elicit blocking antibodies for the SIV virus before it enters cells. Vaccination consisted of two DNA inoculations at months 0 and 2 to prime the vaccine response and then two booster inoculations at months 4 and 6. The booster vaccine was Modified Vaccinia Virus Ankara (MVA), an attenuated poxvirus expressing HIV proteins.

Six months after vaccination, both vaccinated and unvaccinated animals were exposed to SIV through 12 weekly exposures, resulting in an 87 per cent per exposure efficacy and 70 per cent overall protection. Over the following two years, uninfected animals were exposed multiple times in two more series, resulting in 82 per cent and 84 per cent per exposure efficacy during the second and the third series, respectively. “It is impressive to note that protection could be observed against both neutralization sensitive and neutralization resistant viruses,” says Dr. Amara. Neutralization is the process by which some antibodies can block virus infection.

Modified bone drug kills malaria parasite

A chemically altered osteoporosis drug might be useful in fighting malaria, reports a new study by researchers at University of Illinois, the United States. Unlike similar compounds tested against many other parasitic protozoa, the drug readily crosses into the red blood cells of malaria-infected mice and kills the malaria parasite. The researchers, led by chemistry professor Dr. Eric Oldfield, found that the drug works at very low concentrations with no observed toxicity to the mouse. The researchers discovered the drug by screening a library of about 1,000 compounds used in earlier efforts to target an important biochemical pathway (known as isoprenoid biosynthesis) in cancer and in disease-causing organisms.

BPH-703, the new drug candidate, inhibits a key enzyme in isoprenoid biosynthesis that enables the malaria parasite to sustain itself and defend itself from the host immune system. The lead compounds of BPH-703 are chemically modified forms of the osteoporosis drugs Risedronate and Zoledronate that block isoprenoid biosynthesis but do not get across the membrane of red blood cells to get to the parasite. The modified forms include a long lipid tail that helps them pass through the lipid-rich membrane of red blood cells, and also enhances the drug’s ability to bind to the target enzyme, geranylgeranyl diphosphate synthase (GGPPS).

A safe way to repair sickle cell disease genes

Researchers at the Salk Institute for Biological Studies, the United States, have developed a way to use patients’ own cells to cure sickle cell disease and potentially many other disorders caused by mutations in a gene that helps produce haemoglobin. The technique uses cells from a patient’s skin to generate induced pluripotent stem cells (iPSCs), which are capable of developing into various types of mature tissues, including blood. The scientists say their method, which repairs the beta-globin gene (HBB), avoids gene therapy techniques that can introduce potentially harmful genes into cells. The new technique also appears to be more efficient than other methods tested to date, the researchers say.

Sickle cell disease can be cured through stem cell or bone marrow transplants, but there is a high risk that recipients of transplants will reject the donated marrow or cells. The Salk researchers attempted to devise a safe method to use iPSCs generated from the patient’s cells to correct the mutant HBB gene. As about 500 other disease-causing mutations have been identified in the HBB gene, correcting the gene could potentially cure a multitude of HBB-related diseases.

Traditional iPSC generation and gene therapy techniques have been proved potentially unsafe, say the researchers, because of inefficiency and the presence of transgenes. Mr. Keiichiro Suzuki, a research associate and first author of the study, says: “We wanted to fix the mutation in such a way that it does not leave any unwanted traces in a patient’s genome.” To do that, the researchers used a two-step approach. First, they took adult skin cells from a patient with an HBB mutation that causes the sickle cell disease. They used six genes to coax these cells to revert to iPSCs, which could then be developed into blood cells. The genes were introduced into the cells using a technique that avoids the use of virus and insertion of transgenes.

The next step was to repair the HBB gene mutation in the stem cells. To swap the defective gene with a normal copy in the iPSCs, the investigators used a modified adenovirus that, unlike viruses used in other methods, does not replicate itself in the body and does not alter the host cells’ DNA. The viral genes were deleted and replaced with a DNA sequence that contained a normal HBB gene. The modified virus then delivered the new genetic material inside the iPSCs, where the DNA region containing the broken gene was then replaced with the sequence containing the normal gene. By replacing a relatively large region of DNA, the new technique allows the scientists to fix many gene mutations at once, which suggests the method might provide a way to treat hundreds of types of HBB-related diseases.

A modern drug development target

At St. Jude Children’s Research Hospital, the United States, scientists have discovered a key enzyme structure in bacteria. More than 70 years after the first sulpha drugs helped to revolutionize medical care, the scientists have determined at atomic level the mechanism these medications use to kill bacteria. The discovery provides the basis for a new generation of antibiotics that would likely be harder for bacteria to resist and cause fewer side-effects.

The work focused on sulpha drugs and their target enzyme, dihydropteroate synthase (DHPS), which helps micro-organisms make the molecule folate required for the production of DNA and some amino acids. Working with enzymes from Gram negative anthrax bacterium (Bacillus anthracis) and Gram positive plague bacterium (Yersinia pestis), the researchers used a variety of techniques to determine for the first time the key intermediate structure DHPS forms during the chemical reaction to advance folate production. The structure also explains at a molecular level how sulpha drugs function and how resistance causing mutations help bacteria withstand them.

Using first computational methods and then X-ray crystallography, the researchers showed that DHPP binds to a specific pocket in DHPS. Aided by magnesium, the binding promotes the break-up of DHPP and release of pyrophosphate. Two long flexible loops then create an intermediate structure that sets the stage for para-aminobenzoic acid (pABA) to enter and bind in another short-lived pocket, allowing pABA to fuse with the cleaved DHPP. Investigators captured all four actors in the drama in a single crystal structure, including the intermediate cleaved DHPP molecule whose existence was previously unknown.

DNA nanorobot triggers therapeutic responses in cells

Scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University, the United States, have developed a robotic device made from DNA that could potentially seek out specific cell targets within a complex mixture of cell types and deliver important molecular instructions, such as telling cancer cells to self-destruct. The technology might one day be used to programme immune responses to treat various diseases.

Using the DNA origami method, in which complex 3-D shapes and objects are constructed by folding strands of DNA, Dr. Shawn Douglas and Dr. Ido Bachelet created a nanosized robot in the form of an open barrel whose two halves are connected by a hinge. The DNA barrel, which acts as a container, is kept closed by special DNA latches that can recognize and seek out combinations of cell-surface proteins, including disease markers. When the latches find their targets, they reconfigure to cause the two halves of the barrel to swing open and expose its contents, or payload. The container can hold various types of payloads, including specific molecules with encoded instructions that can interact with specific cell surface signalling receptors.

The researchers used this system to deliver instructions, which were encoded in antibody fragments, to two different types of cancer cells, leukaemia and lymphoma. In each case, the message to the cell was to activate its “suicide switch” that eliminates old and abnormal cells. Since leukaemia and lymphoma cells speak different languages, the messages were written in different antibody combinations.

This programmable nanotherapeutic approach was modelled on the body’s own immune system in which white blood cells home in on specific cells in distress, bind to them and transmit comprehensible signals to them to self-destruct. The DNA nanorobot emulates this level of specificity through the use of modular components in which different hinges and molecular messages can be switched in and out of the underlying delivery system. The programmable power of this type of modularity means that the system has the potential to one day be used to treat a variety of diseases.


Genome map speeds up biofuel development

Researchers at the University of Georgia (UGA), the United States, have taken a major step in the ongoing effort to find sources of clean renewable energy by mapping the genomes of two originator cells of Miscanthus (Miscanthus × giganteus), a large perennial grass with promise as a source of ethanol and bioenergy. Dr. Changsoo Kim, a research associate in the UGA Plant Genome Mapping Laboratory, identified a set of approximately 600 bits of Miscanthus DNA that can serve as diagnostic tools. The next step is to determine which pieces of DNA are diagnostic of genes that can make the plant an even better biofuel crop. The work will allow breeders to build on Miscanthus’ natural strengths and remove some of its weaknesses.

The researchers are measuring the height, flowering time, the size of stalks, the dimensions of leaves and the spread from the place of planting of the plants used in the genetic mapping, said Dr. Andrew Paterson, who heads UGA Plant Genome Mapping Laboratory and is also a member of the Bioenergy Systems Research Institute. “Then one can use pretty straightforward statistics to look for correlations between bits of DNA and a trait.”

A significant challenge to producing Miscanthus for biomass in the south-eastern United States is that it tends to flower too soon. Flowering requires nutrients and energy that the plant would otherwise use to grow taller, thicker stalks and leaves. “You don’t want it to flower,” Dr. Paterson said. “You would like it to keep making leaves and stalks and not bother with reproduction. Nature tells it not to do that.” The genetic map will allow the researchers to locate Miscanthus genes responsible for flowering and prevent it from happening too early in the growing season. That will leave farmers with tall, hearty plants that will yield the most biomass possible.

Biomarkers for heat-tolerant cauliflower

Professor Huang Hao-Jen of life science at National Cheng Kung University (NCKU), Taiwan Province of China, developed the technology of molecular detection of genetic markers in heat-tolerant cauliflower for assisting the selection of breeding to ensure year-round supply. Prof. Huang studied the production of floral head in high temperatures and developed several molecular markers to distinguish the heat-tolerant cauliflower. “Heat stress due to high ambient temperatures is an important agricultural problem in the world. High temperature exposures result in floral abortion on many plant species, including bean, broccoli, cauliflower, cotton, pea, pepper, and tomato,” Prof. Huang noted. The technology has been successfully transferred to a private company.

Taking maize off steroids makes it sturdy and female

A researcher at Purdue University, the United States, has taken maize off steroids and found that the results might lead to improvements in the crop. Mr. Burkhard Schulz, an assistant professor of horticulture and landscape architecture, wanted to understand the relationship between natural brassinosteroids – a natural plant steroid hormone – and plant architecture, specifically plant height. Mr. Schulz said corn could benefit by becoming shorter and sturdier, but the mechanisms that regulate those traits are not fully understood.

As suspected, Mr. Schulz found that when maize loses the ability to produce brassinosteroids, it becomes a dwarf. Another feature, however, caught him off guard: the plants without the naturally occurring steroids could not make male organs – they had kernels where the tassels should be. That could be a cost-saving discovery for the seed industry. Hybrid seed producers must painstakingly remove the male pollen-producing tassels from each plant so that they do not pollinate themselves. Mr. Schulz said maize plants that produce only female organs would eliminate the detasseling step.

Mr. Schulz used a multi-step process to determine the role of brassinosteroids in height and, later, sex determination. He wanted to ensure that light and addition of gibberelic acid (GA3), a hormone that promotes cell growth and elongation, would not eliminate the dwarfism. He gathered known maize mutants with short mesocotyls (the first node on a maize stalk). Mr. Schulz suspected that even dwarf plants that produced brassinosteroids would have elongated mesocotyls if grown in the dark as they stretched for light, a trait typical of all brassinosteroid mutants. He also added GA3 to the plants to ensure that a deficiency of that hormone was not causing the dwarfism.

The dwarf plants that did not grow in the dark or with the addition of GA3 were compared with regular maize plants that had been dwarfed by subjecting them to a chemical that disrupts the creation of brassinosteroids. Both exhibited short stalks with twisted leaves and showed the feminization of the male tassel flower. While Mr. Schulz expected brassinosteroids to affect plant height, he said he did not expect those steroids to affect sex determination. It is not know if this is a special case for maize or it is the same in other plants. “If it is the same in other plants, then it should be useful for creating plants or trees in which you want only males or females,” Mr. Schulz said.

Genome-scale model of rice genes

The first genome-scale model for predicting the functions of genes and gene networks in a grass species has been developed by an international research team that includes scientists with Joint BioEnergy Institute (JBEI) of the United States Department of Energy (DOE). This systems-level model of rice gene interactions called the RiceNet should help speed up the development of new crops for the production of advanced biofuels, as well as help boost the production and improve the quality of rice.

“With RiceNet, instead of working on one gene at a time based on data from a single experimental set, we can predict the function of entire networks of genes, as well as entire genetic pathways that regulate a particular biological process,” says Ms. Pamela Ronald, a plant geneticist with JBEI, where she directs the Grass Genetics programme, and with the University of California (UC) Davis, where she is a professor of plant pathology at the Genome Centre. “RiceNet represents a systems biology approach that draws from diverse and large datasets for rice and other organisms,” she said.

According to Ms. Ronald, RiceNet builds upon 24 publicly available data sets from five species as well as an earlier mid-sized network of 100 rice stress response proteins that her group constructed through protein interaction mapping. “We have conducted experiments that validated RiceNet’s predictive power for genes involved in the rice innate immune response,” Ms. Ronald says. She and her team also demonstrated that RiceNet can accurately predict gene functions in another important monocotyledonous crop species, maize. A RiceNet website now available is open to researchers from all over the world.

Improving crops from the roots up

Scientists at the University of Nottingham, the United Kingdom, have shown that root growth can be altered in Arabidopsis thaliana, or thale cress, by controlling an important regulatory protein. The work was carried out by an international research team, led by scientists from the Plant Systems Biology Department in the life sciences research institute VIB and Ghent University in Belgium. Scientists from Wake Forest University, the United States, and the Albrecht-von-Haller Institute for Plant Sciences, Germany, also participated in the study.

The scientists modulated levels of the protein, transcription factor WRKY23, in plants, analysed the effects on root development and used chemical profiling to demonstrate that this key factor controls the biosynthesis of important metabolites called flavonols. Altered levels of flavonols affected the distribution of auxin, a plant hormone controlling many aspects of development, which resulted in impaired root growth.

The results of the research can now be used to produce economically valuable new plant lines that have an improved root system, making them better able to resist environmental changes which could lead to plant damage or poor yield. In addition, WRKY23 was previously found to play a role in the way plants interact with types of nematode parasites, which could lead to further research into how to prevent attacks from the creatures during the early stages of plant growth.


Bio-Nano-Geo Sciences: The Future Challenge

The book focuses on the opportunities and challenges facing science and technological research in India in the second decade of the 21st century. In particular, developments in the bio-, nano- and geosciences are reported, covering topics as varied as the biological route to nanotechnology, river response to climate change, ethics in biomedical research and the pharmacoscintigraphic evaluation of nanoparticle drug delivery systems.

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

Biomaterials and Stem Cells in Regenerative Medicine

This book provides all salient aspects dealing with the basic science involved in structure and properties, techniques and technological innovations in processing and characterizations, and applications of biomaterials and stem cells in tissue regeneration. The coverage ranges from fundamental principles to current technological advancements in the major field of regenerative medicine at the macro/micro/nano/molecular scales.

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

Regenerative Biology and Medicine, Second Edition

This fully-revised edition has been re-organized to highlight the different facets of regenerative biology and provide readers with an overview of the basics with a link to modern, clinically oriented research and application. Coverage of a plethora of tissues and systems is complemented by information about the developmental plasticity of adult stem cells, the biology and application of embryonic stem cells and induced-pluripotent stem (iPS) cells, and the regeneration of appendages.

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


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