VATIS Update Biotechnology . Oct-Dec 2016

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Biotechnology Oct-Dec 2016

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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Sanofi’s dengue vaccine approved in 14 nations

Sanofi-Pasteur, France, the vaccines global business unit of Sanofi, has announced that their dengue vaccines have received approval in 14 countries. Recent approvals for Dengvaxia granted by health authorities are those from Indonesia, Thailand and Singapore. To date the vaccine is approved in Mexico, The Philippines, Brazil, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Indonesia, Thailand and Singapore. “We’re pleased to see the growing medical and public health recognition for the vaccine,” said Su Peing Ng, at Sanofi Pasteur.

“With this new tool in hand, public health communities in dengue-endemic countries now have additional means to achieve the WHO objectives for 50 per cent reduction in mortality and 25 per cent reduction in morbidity due to dengue by 2020,” added Su Peing Ng. Notably, the Latin American Society for Pediatric Infectious Diseases recently published its support for dengue vaccination. National medical societies in Indonesia, Brazil and Mexico recently also recommended vaccination with Dengvaxia, a company said.

In the clinical study population nine years old and older, the dengue vaccine has been documented to prevent two-thirds of dengue cases due to all four serotypes of dengue. The dengue vaccine also prevented 8 of 10 hospitalizations due to dengue and 93 per cent of serious dengue cases like the deadly hemorrhagic form of the disease, over the 25-month study follow-up period of the large-scale efficacy studies conducted in 10 endemic countries in Latin America and Asia.

Nobel prize for work on cell recycling

Yoshinori Ohsumi of Japan has won the Nobel Medicine Prize for his pioneering work on autophagy – a process whereby cells “eat themselves” – which when disrupted can cause Parkinson’s and diabetes. A fundamental process in cell physiology, autophagy is essential for the orderly recycling of damaged cell parts and understanding it better has major implications for health and disease, including cancer. Mr. Ohsumi’s discoveries “have led to a new paradigm in the understanding of how the cell recycles its content”, the jury said.

Researchers first observed during the 1960s that the cell could destroy its own contents by wrapping them up in membranes and transporting them to a recycling compartment called the lysosome – a discovery that earned Belgian scientist Christian de Duve a Nobel Medicine Prize in 1974. It was de Duve who coined the term “autophagy”, which comes from the Greek meaning self-eating. In what the jury described as a “series of brilliant experiments in the early 1990s”, Mr. Ohsumi used baker’s yeast to identify genes essential for autophagy.

He then went on to explain the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in human cells. Mr. Ohsumi’s findings opened the path to understanding the importance of autophagy in many physiological processes, such as how the body adapts to starvation or responds to infection. Mr. Ohsumi (71) received a PhD from the University of Tokyo in 1974. He is currently a professor at the Tokyo Institute of Technology. He is the 23rd Japanese national to win a Nobel prize, and the sixth Japanese medicine laureate.

India seeks greater market access in Japan

Seeking greater market access for the Indian pharmaceuticals sector in the Japanese market, Commerce Minister Nirmala Sitharaman said that the share of India in the Japanese drug market continued to be below par and limited mostly to active pharmaceutical ingredients (or APIs – raw materials for drugs). She said the demand for generic medicines in Japan and India’s capability to meet this demand can prove a win-win for both countries.

“The Japanese pharmaceutical market offers a huge untapped potential for Indian pharma industry. India’s strength in pharma sector is well established. This, coupled with the decision of Government of Japan towards attaining an 80 per cent share of generic medicines by 2018, should provide an opportunity for the generic drug industry of India,” quoted Ms. Sitharaman. Indian companies should use the India-Japan Comprehensive Economic Partnership Agreement (CEPA) much more to boost exports to Japan, she said at a seminar.

The minister voiced concern over India’s trade deficit with Japan increasing from $3.1 billion before the CEPA was inked in 2011 to $5.2 billion thereafter. She said there was a need to address implementation issues of CEPA. For example, Japan had accorded preferential tariff to fish surimi from India. A negligible amount of an imported cryo-protectant, TSPP, is applied for preservation. Though the value of the TSPP is less than 0.5 per cent of the overall product cost, it is precluded from CEPA benefits as the ‘product is not of Indian origin’, she pointed out.

Medical, agri-biotech start-ups in India

After having T-Hub (Telangana Hub) as India’s largest incubator for startups, Hyderabad has another Innovation Hub (iHub) to promote start-ups in the fields of medical and agricultural biotechnology. The Council of Scientific and Industrial Research – Centre for Cellular and Molecular Biology (CSIR-CCMB) have launched this innovation hub.

The iHub is a five-storey building with advanced laboratory equipment for research and innovation. The 40,000-sq ft incubation center will house more than five start-ups per floor. It will offer a platform for translating ideas into technologies and provides a place for start-ups that seek to commercialise medical and agricultural biotechnology, said Rakesh Mishra, director of CCMB.

Pact to promote biological standardization

National Institute of Food and Drug Safety Evaluation (NIFDS), Republic of Korea, has inked a deal with National Institute of Biological Standards and Control (NIBSC), the United Kingdom, to promote and standardize biological medicines and diagnostics, and for maintaining excellence in technical expertise and knowledge. The deal aims to promote biological standardization through international collaborative studies, and to pursue areas of mutual benefit, from access to, optimization of processing and transport of material, to building regulatory competence by exchange of scientific experts and joint workshops.

The memorandum of understanding (MoU) also helps to enhance the global reach for both sides and highlights the role NIBSC plays in assuring the quality of biological medicines around the world. The pact was finalized in a recent event hosted by the World Health Organization’s annual Expert Committee on Biological Standardization (ECBS) conference in Switzerland. The event is considered as a major event in the field of global standardization of biological medicines.

“The MoU is an exciting foundation for closer cooperation between the two institutions. We operate in a global environment and this is an excellent example of the international visibility and engagement both of NIBSC and NIFDS. It further develops a fruitful relationship that both Institutes have established and maintained over many years,” said Dr Christian Schneider, at NIBSC. The NIFDS and NIBSC, as WHO CC, also have been collaborating for the improvement of global public health, particularly, in the area of biological standardization.

China opens national gene bank

China’s first national gene bank, claimed to be the largest of its kind in the world, has officially opened to store and carry out research on hundreds of millions of genetic samples. The centre, dubbed China’s Noah’s Ark by mainland media, aims to collect 300 million genetic samples at its base in Shenzhen when all two phases are complete. The much anticipated platform is to preserve, manage and utilise the genome data and biological samples of Chinese characteristics.

With an investment of 780 million yuan (HK$900 million) for phase one, the China National GeneBank was the fourth of its kind after similar centres in the United States, Britain and Japan. China’s bank will share data with the other three. The site had 10 million gene samples and would include a biological database, samples of living organisms, plus a genome editing platform. It is the largest gene bank of its kind in the world, with a library of animal, plant, microorganism and human body cell samples.

Genetic information stored includes a cancer database with 3,000 samples, information on 50,000 genome mutations, and databases on birth defects, plants, birds and crops. Dozens of refrigerators can store samples at temperatures as low as minus 200 degrees Celsius, while researchers have access to 150 domestically developed desktop gene sequencing machines and a US$20 million Revolocity machine, known as a “supersequencer”. The gene bank will be administered by a council of government agencies, and the Beijing Genomics Institute.

Overcoming antimicrobial resistance

Representatives from countries in Asia and the Pacific have pledged to take immediate action to combat the spread of antimicrobial resistance (AMR). The pledge was made with the support and collaboration of the U.S. Food and Agriculture Organization (FAO), the World Organisation for Animal Health (OIE) and the World Health Organization (WHO). It reaffirms a wider commitment to combat AMR and increase awareness about the scale of the problem in order to stop the emergence and accelerating misuse of antimicrobial medicines in humans and animals.

AMR occurs when microorganisms develop resistance to antimicrobials, making illnesses in humans and animals harder to treat. Overuse and misuse of antimicrobials in both, as well as in plants, are causing an increase in cases of AMR globally. When occurring in farm animals, where farmers often routinely give antibiotics to their livestock, such resistance can be transferred to humans through the food chain or other routes.

Earlier this year, the O’Neill Report, commissioned by the Government of the United Kingdom of Great Britain and Northern Ireland, declared that action to fight AMR was needed immediately in order to head off a human death toll in Asia of up to five million annually by 2050. The issue is so serious that, in September, the United Nations General Assembly recognized this immense threat and mobilized a global response and joint action through the UN specialized agencies and others.

India’s biotech programmes

To apply science to boost rural economy, the Government of India has launched two new programmes – Biotech-KISAN and Cattle Genomics. “The intent of the programmes is to form a network to farmers directly with the scientists and experts,” said Union Science and Technology Minister Harsh Vardhan. The Minister in his address said the Prime Minister’s emphasis “on the importance to work on the problems faced by our farmers is a great motivation factor for the scientist community”.

The second programme ‘Cattle Genomics’ will focus on livestock yield. Explaining Biotech-KISAN (Krishi Innovation Science Application Network), the Minister said the programme focuses on the small, least educated marginalised farmers and women farmers. This scheme will connect farmers with science in the 15 agro-climatic zones. In each of these 15 regions, a farmer organisation will be the hub connected to different science labs, Krishi Vigyan Kendra and State Agriculture Universities co-located in the region.

The hub will reach out to the farmers in the region and connect them to scientists and institutions. The minister added that the network will have a communication cell to make radio and TV programmes. Adding the demand for animal food products in India will increase by 2020, and the second programme Cattle Genomics would focus on selective breeding of the native livestock. The genomic selection will also ensure high-yielding, disease-resistant, resilient livestock.

Biotechnology report in developing countries

The first report on biotechnology in developing countries revealing an overall picture of their biotechnology growth and competitiveness has been released on November 15 on the 27th TWAS General Meeting held in Rwanda. The report was organized by CAS-TWAS Centre of Excellence for Biotechnology (CoEBio), a jointly supported center by Chinese Academy of Sciences (CAS) and the World Academy of Sciences for the advancement of science in developing countries (TWAS).

Released by Professor LI Yin, director of CoEBio, this report focused on scientific publications and patents in 32 categories of industrial, agricultural and medical biotechnologies covering 141 developing countries during the time from 2004 to 2014, as well as collaborations among those countries.

“This report is the first extensive document summarizing the development status of a specific technology area in the developing world,” said BAI Chunli, President of CAS and TWAS.

The report reveals that among the 141 developing countries, 128 countries have references published in biotechnology and only 30 countries have patents granted. In the five regions of TWAS, TWAS East and South East Asia and Pacific Region and TWAS Sub Saharan Africa Region (TWAS-SSA) have the most references and patents; while, TWAS-SSA has the most active cooperation.


Biofuels to drive growth in biotech market

According to the new report by Grand View Research (GVR), the United States, the global white biotechnology market is expected to reach $487.08 billion (€442.5bn) by 2024, growing at a compound annual growth rate of 10.2% with biofuels spearheading the market. According to GVR, rising awareness and emphasis for the adoption of greener and environment-friendly technologies in various end-use industries is expected to drive the market over the next eight years.

Biofuels accounted for over 35% of the market in terms of revenue on account of rising government regulations to include the product in combination with conventional energy sources, including diesel and gasoline. Growing product use in the agricultural sector is likely to drive the demand over the next eight years, and the biofuels segment is expected to grow at a CAGR of over 9% from 2016 to 2024.

Rising biodiesel demand as a raw material for the manufacturing of resins and polymers will fuel industry growth over the forecast period. Advantages such as the ability to use the product directly in any unmodified diesel engine coupled with reduced particulate emissions are likely to fuel industry growth. Volatility of crude oil prices is expected to encourage various manufacturers in the market to increase biofuel production over the next eight years, which in turn will propel technology demand.

Biosimilars to boost India’s pharma growth

According to a study report released by Assocham, India, with the government’s new initiative of enabling ease of doing business in the country, the Indian pharma cos are expected to reap good benefits from the biosimilar sector in the next 15 years. The study stated that the biosimilars would offer more than $240 billion global opportunity for Indian pharma sector. Indian biosimilars industry had crossed $300 million in the year 2015 of which the domestic sales reported at $250 million while $50 million are contributed from the export component.

“India had witnessed a combined annual growth rate of 14 per cent both in domestic and export markets,” revealed the report. Biosimilars are drugs designed to have properties similar to a biological drug that has previously been licensed. It is also sometimes referred to as follow-on biologic or subsequent entry biologic used as a biologic medical product which is almost an identical copy of an original product that is manufactured by a different company.

In fact, the biosimilars are officially approved versions of original “innovator” products, and can be manufactured when the original product’s patent expires. Unlike the generic drugs, biologics generally exhibit high molecular complexity, and may be quite sensitive to changes in manufacturing processes. Major drivers of biosimilars markets can be regulatory policy and increased affordability that biosimilars offer. The domestic market is expected to grow at an accelerated pace and reach the set target by 2030.

Monsanto licenses CRISPR/Cas9 technology

Monsanto, the United States, has signed a nonexclusive global license with the Broad Institute of MIT and Harvard, the United States, for agricultural applications of its CRISPR/Cas genome-editing technology. The value of the agreement and other terms were not disclosed. Monsanto – which is being acquired by Bayer for $66 billion – and the Broad Institute said the agreement is expected to be applied toward improved crops.

According to Monsanto, “Genome-editing technologies, such as CRISPR/Cas, offer a way for scientists to promote site-directed integration of specific genes as well as the opportunity to enhance beneficial or remove undesired plant characteristics. These techniques will enable plant breeders to deliver better hybrids and varieties more efficiently”.

The license “provides access to an exciting tool for our growing body of genome-editing research,” added Dr. Tom Adams, at Monsanto. “Genome-editing technology is complementary to our ongoing discovery research and provides an incredible resource to further unlock our world-leading germplasm and genome libraries.”

Scientists collaborate to design future crops

Three teams of UK and USA researchers have begun a programme of novel research to revolutionise current farming methods by giving crops the ability to thrive without using costly, polluting manufactured fertilisers. The three highly innovative projects includes: searching the planet for a lost bacterium with special, sought-after properties; using synthetic biology to create a new intracellular machine allowing plants to produce fertiliser themselves; and engineering beneficial relationships between plants and microbes.

$8.86M of Biotechnology and Biological Sciences Research Council (BBSRC) and US National Science Foundation (NSF) funding has been awarded following an ‘Ideas Lab’ to generate new approaches that address growing global food demand, which will need 190.4M tonnes of nitrogen-fertiliser by 2015.

Producing artificial fertilisers is costly and uses vast amounts of fossil fuel. Fertiliser use also generates environmental problems such as the runoff of fertiliser into rivers and emissions of nitrous oxide, a greenhouse gas with a much greater global warming effect than carbon dioxide. This funding is aimed at generating innovative technological stepping stones that will reduce the need for fertiliser by enabling crops to fix their own nitrogen.

Bayer clinches $66 billion bid with Monsanto

Drug and crop chemical maker Bayer, Germany, has clinched a $66 billion takeover of seeds company Monsanto, the United States, ending months of wrangling with a third sweetened offer that marks the largest all-cash deal on record. The $128-a-share deal, up from Bayer’s previous offer of $127.50 a share, has emerged as the signature deal in a consolidation race that has roiled the agribusiness sector in recent years, due to shifting weather patterns, intense competition in grain exports and a souring global farm economy.

The transaction includes a $2-billion break-up fee that Bayer will pay to Monsanto should it fail to get regulatory clearance. Bayer expects the deal to close by the end of 2017. Bayer said it was offering a 44-percent premium to Monsanto’s share price on May 9, the day before it made its first written proposal. It plans to raise $19 billion to help fund the deal by issuing convertible bonds and new shares to its existing shareholders, and said banks had also committed to providing $57 billion of bridge financing.

Japanese firm invests in medical research

With a view to curb the menace of malaria and tuberculosis (TB), Global Health Innovative Technology Fund (GHIT Fund), Japan, has issued funding totaling $11.4 million for six research projects that aim to fight malaria and tuberculosis. As per the company, nearly $1.8 million will be spent of developing anti-malaria drugs. The research is an on-going project carried out by a partnership between Swiss-based Medicines for Malaria Venture (MMV), a product development partnership in the field of antimalarial drug research, and Daiichi Sankyo, Japan.

Daiichi sankyo said that the research aims to identify and develop new drugs that could cure malaria-infected patients of both Plasmodium falciparum and Plasmodium vivax with a single dose. Apart from this, GHIT Fund has made two new investments into tuberculosis research. The first was to a research group comprising scientists from Japan, Malaysia, Mexico, and Chile, for the development of an early-stage TB vaccine that would be given intranasally, making it easier to administer and less costly than the standard injectable vaccine.

GHIT Fund has also provided $200,000 in funding for researchers at the Japan-based RIKEN Center for Life Science Technologies and the United Nations’ International Center for Genetic Engineering and Biotechnology, who are studying how tuberculosis survives and replicates in humans-particularly in those who, while infected with latent tuberculosis, stay immune their entire lives. GHIT also said that nearly $7.5 million of the funds will be allocated for malaria research conducted by Japan’s largest pharmaceutical company Takeda Pharmaceuticals.


Researchers study genetic diversity

Scientists from Tohoku University’s Tohoku Medical Megabank Organization (ToMMo), Japan, have recently completed their research about genetic diversity and metabolome. In their analyses, researchers found the relationship between structural variants of enzymes and metabolic phenotypes in the human population.

Researchers identified five associations between metabolites and gene variants. Four of the gene variants are known to be related to metabolic diseases. The residues substituted by these variants are located in peripheral regions of the catalytic sites or related regulatory domains of enzymes.

ToMMo will study environmental and genetic influence on individual differences of proteomics and metabolomics. ToMMo aims to discover useful biomarkers for disease prevention and early diagnosis through the identification and quantification of metabolites in blood. Such studies can contribute to the advancement of personalized prevention and treatment of diseases, as well as the identification of disease mechanisms and development of new therapeutics.

Genomics of local adaptation from coral

For the first time, scientists from University of Texas (UT), the United States, have measured the genomic divergence that occurs as two populations of the same species adapt to two different environments. Researchers observed the phenomenon among populations of mustard hill coral, Porites astreoides, common in the Florida Keys. Scientists were able coax genomic tinkering by moving coral samples from their home to a new site.

Experiments revealed samples from coral populations living closer to shore made more genomic changes than samples of the same species collected from populations farther from the coast. An organism’s genome is made up of the genes it turns on or expresses. Scientists have previously measured differences in the amount of specific genes expressed by two divergent populations of the same species, but the latest research proves separate populations of the same species can turn different genes on and off.

This genetic flexibility enabled closer-to-shore coral to not only better adapt to new environs, but also withstand environmental stressors. Samples from more adaptive coastal coral populations were more likely to survive induced bleaching than samples from farther ashore. Researchers credit their revelations to a more wide-angle approach.

Targeting the noncoding genome

Demonstrating yet another basic research application of CRISPR, two teams at Massachusetts Institute of Technology (MIT), the United States, Broad Institute of MIT and Harvard, the United States, and have independently reported scaled up CRISPR interference (CRISPRi) and CRISPR/Cas9 noncoding genomic screens. Researchers used a large single guide RNA (sgRNA) library to identify noncoding elements that affect the regulation of genes that confer cancer drug resistance.

Researchers used a high-throughput CRISPRi screen to find noncoding regulatory elements within a 1 megabase distance of two disease-related genes. While researchers have previously used the CRISPR/Cas9 system to directly validate previously identified noncoding genomic elements in vivo, the current studies describe larger screens and identify novel noncoding sites. The Broad’s Feng Zhang and colleagues conducted a 715 kilobase-wide CRISPR/Cas9 screen using a library of 18,000 sgRNAs to tile within 100 kilobases surrounding three genes: CUL3, NF1, and NF2.

The researchers identified noncoding sites that, when mutated, resulted in lower expression of one of the genes. The promoter and enhancer elements that regulate these genes are of interest because loss-of-function mutations related to each have been previously linked to resistance to vemurafenib, a drug used to treat BRAF V600E-mutated metastatic melanoma. Rather than synthesizing individual sgRNAs, the team printed the individual RNAs on a solid array like the ones used for hybridization studies, but then cleaved the RNAs and cloned them into lentiviral vectors.

Decoding Japanese morning glory genome

Researchers in Keio University, Japan, have successfully decoded the entire Japanese morning glory genome. Japanese morning glories (Ipomoea nil) are traditional garden plants that are popular in Japan. You can see the flower in many Japanese gardens in the summer. Further, mutants are known to frequently appear in morning glories due to the actions of “jumping genes”, called transposons.

From the Edo period (about 200 years ago), morning glories with strange shaped flowers and leaves have been bred and appreciated, and this has developed into a unique gardening culture in Japan. Because of the popularity of these “mutant morning glories”, a lot of natural mutants have been collected. In modern times, by analyzing these mutants in detail, researchers have found a number of genes that determine flower and leaf shapes as well as flower colors and patterns.

The research group has deciphered the entire genome of the Japanese morning glory standard line. “A high-quality nearly complete genome sequence was obtained, leading to identification of the coding sequences of the approximately forty three thousand morning glory genes, as well as the number and distribution of the transposons which produce the stunning variety of morning glory colors and shapes,” said Professor Yasubumi Sakakibara at Keio University.

Genome of black blow fly mapped

Researchers at the School of Science at Indiana University-Purdue University Indianapolis (IUPUI), the United States, have sequenced the genome of the black blow fly, an insect commonly found throughout the United States, southern Canada and parts of northern Europe. Black blow flies have environmental, medical and forensic uses, functioning as nature’s recyclers, as wound cleansers and as forensic timekeepers. They have a blue or green sheen and are similar in size to common houseflies.

The female genome was found to contain 8,312 genes; the male genome had 9,490 genes. “There is nothing special about black blow flies, but that lack of uniqueness is why scientists are interested in studying them,” said Christine Picard, at IUPUI. Black blow flies are active insects that perform three tasks that benefit humans: recycling carrion, debriding human wounds and laying eggs on freshly dead bodies. They have no harmful or parasitic behaviors. Black blow flies feed on decaying flesh and help consume dead vertebrates throughout the environment.

Black blow fly larvae, or maggots, are used medically to debride human wounds, as the insects physically remove dead tissue while simultaneously excreting antimicrobial compounds into the wound. With an excellent sense for smelling recently dead tissue, black blow flies are usually the first insects to colonize a human body, frequently within minutes after death. Females lay eggs on recently deceased corpses, setting a “clock” that enables forensic investigators to estimate the postmortem interval, or minimum time since death.

Tool for genetics research

Researchers at Princeton University, the United States, and Harvard University, the United States, have developed a way to produce the tools for figuring out gene function faster and cheaper than current methods. The function of sizable chunks of many organisms’ genome is a mystery and figuring out how to fill these information gaps is one of the central questions in genetics research.

Researchers are the first to create a collection quickly and affordably, doing so in less than a month for several thousand dollars. Their strategy, called “Knockout Sudoku,” relies on a combination of randomized gene deletion and a powerful reconstruction algorithm. Though other research groups have attempted this randomized approach, none have come close to matching the speed and cost of Knockout Sudoku.

Their approach began with steep pizza bills and a technique called transposon mutagenesis that ‘knocks out’ genes by randomly inserting a single disruptive DNA sequence into the genome. This technique is applied to large colonies of microbes to ensure the likelihood that every single gene is disrupted. The team started with a colony of about 40,000 microbes for the bacterium Shewanella oneidensis, which has approximately 3,600 genes in its genome. Using their expedient strategy, they created a collection for microbe Shewanella oneidensis.

Gene mutation that increase breast cancer

Researchers of the Anthropological Survey of India (AnSI) and the University of Calcutta, Department of Anthropology, India, have found that changes in a particular gene, called the BRCA2 gene, can increase the risk of breast cancer in men. A two-year study, which ended earlier this year, identified certain ‘novel mutations’ in the BRCA2 gene (BRCA refers to breast cancer), which makes men more susceptible to the disease.

While there are a lot of studies on the BRCA1, BRCA2 and other inherited gene mutations resulting in female breast cancer, this is the first study on male breast cancer from this part of the country. Scientists collected samples of blood and tissue from several patients diagnosed with male breast cancer. This was followed by DNA sequencing by which gene expression and novel mutations that could be responsible for the disease were identified.

“If these mutations, which we came across the during our study, are found among normal healthy males, the person is at risk of having the disease any time during his life,” Abhishikta Ghosh Roy, at AnSI. Since breast cancer primaries (lumps) in men tend to be smaller than in women, diagnostic delays are caused. Moreover, since the BRCA2 mutation carriers are found in lymph nodes, men do not feel the pain that would urge them to seek medical intervention. Not only genetic factors, but lifestyle and reproductive factors trigger risks for the disease in men.

Genomics platform to accelerate disease research

Genomic software company, DNAstack, Canada, has announced the launch of its cloud platform to accelerate genetic disease research and precision medicine. DNAstack provides push-button access to state-of-the-art genomics data analysis and sharing to help scientists more quickly and cost-effectively make sense of the world’s exponentially accumulating genomics data and break down barriers to data sharing.

DNAstack is a simple, scalable, secure solution that enables management, analysis, search, and sharing of genomics datasets in the cloud. To accelerate adoption of best practices bioinformatics and open standards in data sharing, DNAstack is offering these features for free, where users pay only for cloud costs incurred for data storage and computation on the Google Cloud.

DNAstack is the first commercial platform to be built on Google Genomics and is compliant with standards developed by the Global Alliance for Genomics & Health (GA4GH). The company is paving the way for an “internet of genomes” that will help connect a global network of data sharing organizations. The path of genomics data from sequencing to medical impact is a long and windy one. DNAstack believes this can be shortened by connecting repositories into shared networks that can be analyzed in real-time.

Arabica coffee genome sequenced

The first public genome sequence for Coffea arabica, the species responsible for more than 70 percent of global coffee production, was released today (Jan. 13) by researchers at the University of California, Davis, the United States. Now available for immediate use by scientists and plant breeders around the world, the new genome sequence has been posted to, the public database for comparative plant genomics coordinated by the U.S. Department of Energy’s Joint Genome Institute. Details of the sequence were presented (Jan. 15) at the Plant and Animal Genome Conference in San Diego.

Sequencing of the C. arabica genome is particularly meaningful for California, where coffee plants are being grown commercially for the first time in the continental United States and a specialty-coffee industry is emerging. “This new genome sequence for Coffea arabica contains information crucial for developing high-quality, disease-resistant coffee varieties that can adapt to the climate changes that are expected to threaten global coffee production in the next 30 years,” said Juan Medrano, a geneticist in the UC Davis College of Agricultural and Environmental Sciences and co-researcher on the sequencing effort.

The sequencing was conducted through a collaboration between Medrano, plant scientists Allen Van Deynze and Dario Cantu, and postdoctoral research scholar Amanda Hulse-Kemp, all from UC Davis. Using sequencing technology developed by Pacific Biosciences of Menlo Park, the UC Davis researchers estimated that UCG-17 Geisha has a genome made up of 1.19 billion base pairs — about one-third that of the human genome.

The study used a combination of the latest technologies for genome sequencing and genome assembly from Dovetail Genomics of Santa Cruz, revealing an estimated 70,830 predicted genes.

Going forward, the researchers will focus on identifying genes and molecular pathways associated with coffee quality, in hopes that these will provide a better understanding of the flavor profiles of Geisha coffee. They have sequenced samples from 22 other Geisha coffee trees to obtain a glimpse of the genetic variation within that variety and among 13 other C. arabica varieties, which also will be important for developing plants that can resist disease and cope with other environmental stresses.


Insulin resistance reversed by protein removal

A team led by Jerrold Olefsky, at UC San Diego School of Medicine, the United States, has shown that by genetically removing Gal3 or using pharmaceutical inhibitors to target it, insulin sensitivity and glucose tolerance could be returned to normal, even among older mice. However, obesity remained unchanged. “This study puts Gal3 on the map for insulin resistance and diabetes in mouse model. Our findings suggest that Gal3 inhibition in people could be an effective anti-diabetic approach,” said Olefsky.

Olefsky and other researchers have been studying how chronic tissue inflammation leads to insulin resistance in type 2 diabetes. In the paper, published in the journal Cell on November 3, researchers explain that inflammation requires macrophages – specialized cells that destroy targeted cells. In obese adipose tissue (fat), for example, 40 percent of cells are macrophages. Macrophages in turn secrete Gal3, which then acts as a signaling protein attracting more macrophages, thus resulting in the production of even more Gal3.

Furthermore, investigators identified bone marrow-derived macrophages as the source of Gal3 that leads to insulin resistance. More importantly, researchers found that Gal3 is secreted by macrophages, and can then cause insulin resistance in liver, fat cells, and muscle cells independent of inflammation. Gal3 has previously been connected to other diseases. Olefsky will continue to study Gal3 depletion as a possible therapeutic target for nonalcoholic steatohepatitis as well as heart and liver fibrosis.

Protein atlas scores nitrogen fixing duet

A group from the University of Wisconsin-Madison, the United States, has detailed more than 23,000 plant and bacterial proteins and the molecular controls by which they execute the beneficial relationship. The atlas, possibly the most exhaustive proteomic inventory of any kind to date, shows in minute detail the interplay of proteins as rhizobia colonize root nodules on the model legume Medicago truncatula.

“We can see deeper into the proteome than ever before. We’re able to use technology to provide an unprecedented view of these proteins,” explained Joshua Coon, a UW–Madison. That new picture, he said, takes our understanding of the mechanics of nitrogen fixation to an unprecedented level of detail. Because proteins are regulated by genes, the new atlas could ultimately help inform a strategy for engineering the nitrogen-fixing ability of legumes into other plants.

The new atlas was compiled using potent new mass spectroscopy technology, says Coon, a leading authority on the technique that permits scientists to parse a sample into its many constituent components and measure them in exquisite detail. The Wisconsin researchers stress that while the new protein atlas will be an important cipher for decoding the molecular details of nitrogen fixation symbiosis, the goal of conferring the trait on plants other than legumes remains in the distant future.

Genes linked to development of atherosclerosis

Researchers at Brigham and Women’s Hospital (BWH), the United States, have found two new potential drug targets for treating arterial diseases such as atherosclerosis. By using proteomics to screen a vast number of molecules, the researchers identified PARP9 and PARP14 – two members of the PARP family of proteins – as regulators of macrophage activation, which has been linked to arterial disease by systems biology.

Though the mechanisms that activate macrophages, a type of digestive white blood cell that targets foreign cells, remain incompletely understood, previous research shows that macrophages play an important role in the development of atherosclerosis and its thrombotic complications.

Masanori Aikawa, at the Brigham, his research fellow Hiroshi Iwata, and colleagues studied atherosclerosis on the protein-level to determine which molecules were most involved in the regulation of macrophages. Once researchers narrowed down their search to these two proteins, they silenced each gene in cultured macrophages and found that tamping down PARP14 increased macrophage activation while tamping down PARP9 had the opposite effect.

DNA-altering technology to tackle diseases

Researchers from Nanyang Technological University (NTU), Singapore, have developed a new protein that can alter DNA in living cells with much higher precision than current methods. This new protein, named iCas, can be easily controlled by an external chemical input and thus solves some of the problems with CRISPR-Cas1, the existing gold-standard for DNA altering. For example, existing Cas enzymes may sometimes alter places in the DNA that result in dire consequences.

With iCas, users now have the ability to control enzyme activity and thus minimize unintended DNA modifications in the cell. In the study, iCas was found to outperform other chemical-inducible CRISPR-Cas technologies, with a much faster response time and an ability to be switched on and off repeatedly. The higher speed at which iCas reacts will enable tighter control over exactly where and when DNA editing takes place.

This is useful in research or applications that demand precise control of DNA editing. For example, in studies of cell signalling pathways or vertebrate development, iCas can precisely target a subset of cells within a tissue (spatial control) or to edit the DNA at a particular developmental stage (temporal control). Developed by a collaboration between A*STAR’s Genome Institute of Singapore (GIS) and NTU, iCas has been published in the scientific journal Nature Chemical Biology.

Researchers identify way to prevent UTIs

Researchers from Washington University School of Medicine (WUSM), the United States, have identified a potential way to prevent chronic urinary tract infections (UTIs). Their research points to a key protein that bacteria use to latch onto the bladder and cause UTIs. According to the scientists, vaccinating mice against the protein reduces the ability of bacteria to cause severe disease.

The study suggests that targeting this protein may prevent the most serious consequences of a very common infection. As part of the current study researchers focused on a protein known as FmlH, which they believed was located at the tip of the pilus, where it would help bacteria stick to the bladder wall. The researchers removed the gene for FmlH from E. coli and then infected the urinary tracts of mice with bacteria with and without the gene.

They found that E. coli lacking FmlH were less likely to establish chronic infections in mice than bacteria with the protein. In the first few days of the infection, the two strains multiplied to similar levels. But by the end of the fourth week, the bacteria without FmlH were 1,000 times less numerous in the bladder and 100 times less numerous in the kidneys than the bacteria with the protein.

New evolution to improve biotech products

In a study published in Nature Biotechnology, scientists from Emory, Children’s Healthcare of Atlanta and Georgia Tech, the United States, proposed that they can improve protein-based drugs by reaching into the evolutionary past,. As a proof of concept for this approach, the research team showed how “ancestral sequence reconstruction” (ASR) can guide engineering of the blood clotting protein known as factor VIII, which is deficient in the inherited disorder hemophilia A.

The authors said that ASR-based engineering could be applied to other recombinant proteins produced outside the human body, as well as gene therapy. Experimental hematologist and gene therapist Dr. Chris Doering, and his colleagues already had some success in addressing these challenges by filling in some of the sequence of human factor VIII with the same protein from pigs.

The research team showed that amino acid changes toward ancestral sequences could make human factor VIII more stable and less likely to be inhibited by recipient antibodies. “This exemplifies how understanding the evolutionary history of a protein can help engineer better versions of the protein for therapeutic use. ASR is a widely accessible strategy that utilizes both known and unknown natural protein diversity to rapidly probe a protein design space that has already been refined by natural selection for beneficial properties,” said Gaucher.


Researchers step closer to cure Parkinson’s disease

Researchers from the Indian Institute of Technology, Bombay (IIT-B) have taken the first successful step at regenerating neurons in a Parkinson mouse model by using mesenchymal stem cells (MSCs) encapsulated in an amyloid hydrogel. The hydrogels which provide scaffolding for stem cells to develop into neurons when implanted in the brain are developed from a special class of proteins called amyloids.

The hydrogel enabled the delivery and engraftment of mesenchymal stem cells in two regions of the mice brain – substantia nigra and striatum – where the cells were injected. “We do not have direct proof that mesenchymal stem cells have become neurons. But the stem cells transplanted at the substantia nigra site were differentiating into neuron-like cells,” said Subhadeep Das from IIT-B. In the case of Parkinson’s, neurons based in the substantia nigra region of the brain release dopamine at the striatum.

Since the connection between the two regions is lost in the case of Parkinson’s, the researchers implanted the stem cells at both the sites. But before transplanting the stem cells encapsulated in the hydrogel into the brain of the mice, the researchers tested the hydrogel in the lab for toxicity. Both neural precursor cell lines and mesenchymal stem cells were cultured in the amyloid hydrogel. And 2D and 3D culture tests for toxicity were carried out for 24-120 hours term and the results compared with a collagen hydrogel, which served as control.

Role of enzyme in regulating blood pressure

In a study scientists from The Feinstein Institute for Medical Research, the United States, and Karolinska Institutet, Sweden, discovered that T-cells capable of producing the neurotransmitter acetylcholine can regulate blood pressure. These T-cells are white blood cells, part of the immune system, which contain an enzyme choline acetyltransferase (ChAT). It is this ChAT enzyme that is responsible for the production of acetylcholine.

Having now identified ChAT cells’ new role and previously knowing that they respond to vagus nerve stimulation, Feinstein Institute researchers will explore using bioelectronic medicine to treat blood pressure and hypertension – a condition that affects more than 70 million Americans. Bioelectronic medicine is a new field of research that uses technology to treat disease and injury.

“Previous studies conducted at the Feinstein Institute found that the immune function could be controlled by neural mechanisms through the spleen, and with this study we were looking to identify triggers that could reach deeper into the smaller arteries to aid with conditions such as high blood pressure. We will develop this finding into new research that we hope will pave the way to new therapies that will improve million lives,” said Kevin J. Tracey, at Feinstein Institute.

Bacteria to detect leaks at carbon capture sites

Researchers at the Scottish Association for Marine Science (SAMS), the United Kingdom, and the University of Oslo, Norway, have found that bacteria and archaea could be used to monitor stored carbon dioxide (CO2) and convert it into useful products, such as ethanol and acetate. According to them, the new bioinformatics tools would enable researchers to read shifts in microbial community genetics – making it possible to detect potential CO2 leaks – and how such analyses could contribute to making large-scale capture and storage of CO2 feasible.

“One of the biggest concerns with carbon capture storage is the environmental impacts if there is a leak, would we know about it, how would we detect it, and what would the environmental implications be,” said Natalie Hicks, at SAMS. In addition to physical methods of monitoring CCS sites, such as measuring CO2 levels, which currently lack clear protocols and can be difficult at remote sites, it should be possible to monitor the bacteria and archaea living in sediment overlying these sites to detect potential leaks.

They point to a simulated CO2 leak experiment previously conducted in a sub-seabed reservoir off the west coast of Scotland that detected changes in the microbial communities around the reservoir, before other organisms were visibly affected. The researchers note that this approach will require more information on microbial communities and how they respond to fluctuations in CO2.

New molecule may help fight obesity

Researchers at University of Tennessee, the United States, have identified a new molecule that may help fight obesity and other metabolic diseases by converting ‘bad’ fat to ‘good’ fat. New research suggests that activation of a chemical called Beta-LGND2 by the estrogen receptor Beta (ER-Beta) reduces obesity and metabolic diseases in mice by converting bad or white fat to good or brown fat. This is significant as brown fat increases metabolism and may facilitate weight loss.

“Although there is a general misperception that obesity is not a life-threatening condition, obesity is the underlying cause for several diseases that could result in mortality,” said Ramesh Narayanan, researcher at the University of Tennessee. To make their discovery, Narayanan and colleagues used three groups of mice. One group was fed with normal rodent diet, while two groups were fed with high-fat diet (HFD) to make them obese.

One of the two HFD-fed groups was treated with vehicle, while the other HFD-fed group was treated with beta-LGND2. Beta-LGND2-treated mice were significantly leaner than the other mice fed an HFD. Beta-LGND2-treated mice had higher body temperature and oxygen consumption, indicating higher metabolism rate.

Software to detect mental disorders

The Neuroimaging and Neuro­spectroscopy laboratory of National Centre for Brain Research, India, has developed complete and integrated software that could help early diagnosis of mental health problems. Developed by a team of neuroscientists, the software can quantify a brain neurochemical called γ-Aminobutyric Acid (GABA) through neuroimaging of brain metabolites using Magnetic resonance spectroscopy (MRS).

Titled KALPANA, the software allows visualization and single-click processing of MRS data acquired using a variety of methods. With the incorporation of premade end-to-end processing workflows for a variety of data and use of algorithms that enable accurate estimation of chemical concentrations from the signal and a graphical interphase for its easy interpretation, the software offers distinct clinical scope.

While several signal processing packages do already exist, KALAPNA offers a distinct advantage in three aspects. It can handle a variety of signal types and processing algorithms, it offers versatility for both in-depth interactive use for research purposes and one-click processing for diagnostic purposes and utilises an adapted algorithm to improve the accuracy of quantification thereby increasing clinical value of the package. The package has been made free for academic use.

Scientists create better blood sugar test

Researchers at Harvard Medical School (HMS), the United States, have developed a more precise method for estimating average blood sugar levels that can cut diagnostic errors by more than 50 percent compared to the current widely used but sometimes inaccurate test. “What we currently deem the gold standard for estimating average blood glucose is nowhere as precise as it should be,” said John Higgins at HMS.

Because blood sugar varies by the hour and even by the minute, doctors use the so-called A1C test as a proxy to gauge a person’s average blood glucose level over the previous three months. The A1C test measures the amount of glycated hemoglobin, glucose that sticks to hemoglobin, or oxygen carrier, inside red blood cells, which can live in the body for only three months. The test, however, is somewhat imprecise. It can lead to identical readings for people with different average blood sugar levels.

At the same time, people with similar blood sugar levels can also end up having widely divergent results. These inaccuracies stemmed entirely from individual variations in the life span of a person’s red blood cells. To eliminate the influence of age-related variation, the team developed a formula that factors in the life span of a person’s red blood cells and then compared the age-adjusted blood sugar estimates to estimates derived from the standard A1C test and to readouts of glucose levels measured directly by continuous glucose monitors.


Defying frost and the cold with hormones

Professor Brigitte Poppenberger and her research group at the Biotechnology of Horticultural Crops institute at the Technical University of Munich (TUM), Germany, have investigated the mechanisms used by plants to adapt to external influences. Her research activities have centered on brassinosteroids for quite some time. In earlier work, her group already used common thale cress (Arabidopsis thaliana) as a model plant to demonstrate exactly how this plant hormone, which was identified for the first time in rapeseed in 1979, promotes plant growth.

In order to gain a detailed understanding of their mechanisms, the researchers carried out experiments in which they exposed Arabidopsis plants to slowly decreasing temperatures. Experiments with wild-type varieties in the laboratory showed that as the temperature decreases, the plant reacts by beginning to modify the expression of genes for which DNA is transcribed to RNA within its cells. “This reduces its growth, which increases its chances of survival”, Poppenberger explained, describing the natural protective mechanism of the normal plants.

Fungal infection help researchers

A team of researchers from Centre for Plant Biotechnology and Genomics (CBGP, UPM-INIA), Spain, have revealed how mold from humidity caused by rotting fruits and vegetables unfolds a surprising strategy to infect plants. Researchers has published the results on Alt a1 in the journal Scientific Reports from the Nature group. Alt a1 is a strongly allergenic protein found in certain endophytic fungi species that causes severe asthma. This study provides better understanding of the role played by this protein in the pathogenicity of the fungus.

Additionally, the mechanism identified in plants can also provide information of clinical interest about respiratory diseases and allergies caused by these fungi. Spores of certain Alternaria fungi that appear as mold in plants of most crops are present in the atmosphere throughout the year. Alt a1 is a strongly allergenic protein present in the spores of Alternaria alternata before germination. Alt a1 is responsible for infections and common respiratory conditions and is also considered as the major allergen associated with chronic asthma.

The pathogenic action of this protein is linked to the production of certain toxic compounds and the increasing production of reactive oxygen species by plants that are toxic agents causing cell death. Alt a1 interacts with defense proteins that plants express when are attacked by inhibiting their activity. The Alternaria spores remain on the surface of the plant without inducing symptoms while waiting for the right moment to germinate. When this occurs, the spores provoke a cascade of processes that had been largely unexplored until now.

New kind of local food grows in kitchen

A home appliance that grows the ingredients for a healthy meal within a week from plant cells is no longer science fiction. VTT Technical Research Centre of Finland Ltd’s first 3D-printed CellPod prototype is already producing harvests. VTT and its plant biotechnology research scientists have the vision of developing a home appliance for the markets that makes it possible to grow, healthy Finnish berries in a new way.

Growing plant cells in a bioreactor is not a new idea as such, but only the latest technologies have enabled the development of a plant cell incubator for home use that yields a harvest within a week. VTT’s first CellPod prototype is currently producing a harvest in Otaniemi. The appliance resembles a design lamp and is ideal for keeping on a kitchen table. Researchers are in the process of developing different product ideas in collaboration with consumers, with the aim of commercialising the concept.

The idea of the CellPod concept is based on growing the undifferentiated cells of a plant rather than a whole plant. In other words, only the best parts of a plant are cultivated. These cells contain the plant’s entire genetic potential, so they are capable of producing the same healthy compounds – such as antioxidants and vitamins – as the whole plant. The nutritional value of a cloudberry cell culture, for example, is similar to or even better than that of the berry itself. The taste still needs development: at the moment, it is very mild and neutral.

Cotton disease control with gene technology

China, the largest cotton producers in the world, has made a breakthrough in controlling a major disease of cotton plants using gene technology. After 8 years of research, Chinese scientists with the Institute of Microbiology of Chinese Academy of Sciences (IMCAS) found that gene interference technology can prevent the spread of a pathogenic fungus, the cause of Verticillium dahliae wilt. Verticillium dahliae is a vascular fungal pathogen responsible for devastating many crops.

Led by Guo Huishan, the research group has discovered how the fungus infects the cotton. Based on their findings, scientists have cultivated a new strain of cotton with resistance to verticillium dahliae increased by 22.25 per cent. “Anti-pathogenic fungus cotton will help cotton farmers make more money,” said Guo. The findings have been published in the latest edition of Nature Plants.

Jet fuel from Aussie gum trees

Scientists are a step closer to using Australia’s iconic gum trees to develop low-carbon renewable jet and missile fuel. “Renewable fuels that could power commercial aeroplanes were limited and expensive but a solution could be growing all around us,” said Dr. Carsten Kulheim from the Australian National University (ANU). The study examines how to boost production of monoterpenes to obtain industrial scales of jet fuel from plants.

This includes selecting appropriate species, genetic analysis, advanced molecular breeding, genetic engineering and improvements to harvesting/processing of the oils. Certain monoterpenes commonly found in eucalyptus oils such as pinene and limonene, can be refined through a catalytic process, resulting in a fuel with energy densities suitable for jet fuel. Turpentine from pine trees is another potential source of these monoterpenes, but pines grow more slowly than eucalypts.

Researchers identify gene to stop wheat disease

A multi-institutional team of researchers including Nidhi Rawat, at University of Maryland, the United States, and Michael O. Pumphrey, at Washington State University (WSU), the United States, have achieved a major breakthrough in the cloning of a resistance gene to eliminate wheat scab – a widespread disease responsible for drastic reductions in crop yield as well as millions of dollars in annual losses worldwide.

This discovery has broad implications for the future as a promising source of resistance to not only wheat scab, but a variety of similar host plants affected by the fungal pathogen known as Fusarium graminearum. Ultimately, once the nature of gene action is known, the findings can be applied to control other Fusarium species which causes rot in cucurbit, tomato and potato to name a few. Fusarium graminearum produces a toxin that makes the infected crop unfit for human and animal consumption.

Historically, wheat scab – otherwise known as Fusarium Head Blight – has been a very difficult problem to solve. 20 years of research that includes input from scientists in China and several American Universities has been slow to produce results, with resistance only found in a select group of local Chinese plants. Until now, nothing was known about the Fhb1 gene and its ability to provide broad-spectrum resistance.

Yeast used to convert plant sugars into oils

MIT engineers in the United States have genetically reprogrammed a strain of yeast so that it converts sugars to fats much more efficiently, an advance that could make possible the renewable production of high-energy fuels such as diesel. The researchers, led by Gregory Stephanopoulos, the Willard Henry Dow Professor of Chemical Engineering and Biotechnology at MIT, modified the metabolic pathways of yeast that naturally produce large quantities of lipids, to make them about 30 percent more efficient.

“We have rewired the metabolism of these microbes to make them capable of producing oils at very high yields,” says Stephanopoulos, who is the senior author of the study, which appears in the Jan. 16 issue of Nature Biotechnology. This upgrade could make the production of renewable high-energy fuels economically feasible, and the MIT team is now working on additional improvements that would help get even closer to that goal.

Stephanopoulos and his colleagues began working with a yeast known as Yarrowia lipolytica, which naturally produces large quantities of lipids. They focused on fully utilizing the electrons generated from the breakdown of glucose. To achieve this, they transformed Yarrowia with synthetic pathways that convert surplus NADH, a product of glucose breakdown, to NADPH, which can be used to synthesize lipids. They ended up testing more than a dozen modified synthetic pathways.


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Recent Advancements in Gene Expression and Enabling Technologies in Crop Plants

The book describes current advances on commercial crops and key enabling technologies that will underpin future advances in biotechnology. This book has three sections that encompass knowledge on genetically modified (GM) food crops that are currently used by consumers, those that are anticipated to reach the market place in the near future and enabling technologies that will facilitate the development of next generation GM crops.

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This book examines how biotechnology can improve livestock breeding and farming, and thereby also animal products. The reader will discover which techniques and approaches are currently used to improve animal breeding, animal health and the value of animal products. Particular attention is given to reproduction techniques, animal nutrition and livestock vaccines that not only enhance animal health but also have a significant effect on human health by ensuring safe food procurement and preventing zoonotic diseases.

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