VATIS Update Biotechnology . Mar-Apr 2009

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Biotechnology Mar-Apr 2009

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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India moots innovative funding for biotech, pharma sectors

The Department of Biotechnology (DBT) and the Department of Pharmaceuticals (DoP) of the Indian government are looking to innovative funding to bolster research and make India a destination for drug-discovery. DBT is exploring avenues to fund research, focus on the opportunity of bio-similar products and create infrastructure to scale-up human resources to support a shift to high-end research in the long term, said DBT secretary, Dr. M.K. Bhan, at a recent meet in Mumbai.

DBT has recently got approvals from the Finance Ministry for a Rs 2 billion fund for vaccines that would support a range of programmes including clinical trials, vector development, adjuvant development and intellectual property, he said. Another such funding proposal from DBT is the Rs 3.5 billion corpus, over a three-year period, where soft loans would be given at two per cent interest for bio-similar projects. Stressing on innovative funding through partnerships, Dr. Bhan said, a team from DBT was in the United Kingdom for talks with the Wellcome Trust for a 50 million fund, which would have equal contribution from both parties and will support health technologies.

Similar plans were outlined by DoP secretary, Mr. Ashok Kumar. As part of plans to make India one of the top five global destinations for pharmaceutical innovation, DoP envisaged annual investments of about US$1-2 billion till 2020. The plan was for a public-private partnership where government investment would taper gradually as the private sectors increases, he explained.

Pharmaceutical industry representatives were cautious in their response on these ambitious plans. Research-focused funds set up in the past by the government have taken time to get off the ground and even when they did, the amount available was very little, observed an industry veteran. To help streamline funding, the funding could kick-in for late stages of research. This would take care of transparency and IP issues, as project details are revealed only when filings are public, he added.


Singapore-made biofuel to run cars in Europe, North America

Diesel made from palm oil, vegetable oil and animal fat in Singapore may soon be powering cars in Europe and North America, Finlands Neste Oil said. Neste Oil, which is building the worlds largest biodiesel plant in the city-state at a cost of about US$776 million, said it might market the fuel also in Japan and the Republic of Korea.

The plant will have an annual capacity of 800,000 tonnes when it becomes operational in 2010. It will produce Neste Oils patented NExBTL renewable diesel, which the company claimed is the cleanest diesel fuel in the world. NExBTL, which can be used in all diesel engines, significantly reduces exhaust emissions compared with regular diesel, the company said. The Singapore facility could be beefed up to produce jet fuel from the same feedstock if there was a need, said Neste Oil Deputy CEO Mr. Jarmo Honkamaa. Neste Oil is also building a renewable diesel plant with similar capacity in Rotterdam, the Netherlands, which is expected to come on stream after the Singapore facility.


United States biotech industry applauds Presidents decision on stem cell research

The Biotechnology Industry Organization (BIO) of the United States lauded President Mr. Barack Obamas Executive Order to allow the National Institutes of Health (NIH) to fund research using embryonic stem cells. NIH was previously able to fund research only on a very limited number of stem cell lines. Mr. Jim Greenwood, President and CEO of BIO, said the action to expand NIH funding of stem cell research was a welcome and critical step, while noting that it was only the first step in a very long and complex process to move from the promise of research to the reality of new therapies and cures for patients.

Research on both adult and embryonic stem cells holds great promise to produce new therapies and possibly cures for the millions of patients around the world suffering from cancer, diabetes, Alzheimers, Parkinsons, spinal cord injuries and other life-threatening diseases and conditions. Embryonic stem cell research is also expected to further the development of cell-based therapies by leading to greater scientific understanding of cell differentiation and proliferation.


Cuba plants first GM maize crop

Genetically modified (GM) maize (corn) is being grown for the first time in Cuba as a trial aimed at obtaining high-yield varieties. Three hectares of land have been planted with GM maize, as part of an experiment on transgenic maize FR-Bt1 carried out by the National Centre for Genetic Engineering and Biotechnology (CIGB).

The GM maize is being grown in Yaguajay, Sancti Spiritus, by the Valle de Caonao Company. Mr. Ral Armas, a specialist from the CIGB, said the Cuban variety has been modified to be more resistant to the fall armyworm (Spodoptera frugiperda), the principal pest that affects this crop, and to increase the crops tolerance to pesticides. This variety of transgenic maize features no major modifications to the plant or cob, maintaining its nutritional value and flavour. It needs little maintenance, requiring only watering and spraying with herbicides.

Meanwhile, an international survey of 13 years of GM agriculture up until 2008, released in Nairobi in February by ISAAA, says there is substantial evidence that crops genetically modified to withstand drought, pests and diseases are safe for human consumption.


Canada announces funding for biotechnology project

In Canada, a biotechnology project led by Performance Plants Inc. (PPI), a leading agricultural and biofuel biotechnology development company, will receive up to US$4.9 million in funding from Sustainable Development Technology Canada (SDTC), a not-for-profit corporation. The funds will be used to advance PPIs trait technologies that improve conversion of cellulose into cost-effective biofuels and biochemicals.

We believe our technologies are the critical link to developing a profitable and sustainable clean energy sector that replaces such feedstocks as coal and petroleum with non-food biomass crops, said Mr. Peter Matthewman, PPIs President. PPI has discovered a family of technologies called Enhanced Conversion TechnologyTM (ECT) that alter plant cell walls to significantly improve their conversion into biofuels. The primary use of the SDTC funding will be to develop ECT to improve the amount of releasable glucose and develop these traits in non-food crops to increase their conversion efficiency. The funding will also be used to support the acceleration of PPIs Biomass EnhancementTM and Water Use EfficiencyTM technologies. These yield stabilization technologies will be combined with ECT to further reduce costs by increasing feedstock yield per hectare of land.



GM brinjal to hit market soon

In Hyderabad, India, nearly 200 varieties of brinjal (eggplant or aubergine) were on display recently at a food festival. The focus was on brinjal because this vegetable, which is native to India, could become the first genetically modified (GM) food crop to be allowed in India.

Bt brinjal looks exactly like any other brinjal except that it has bacterial genes that are meant to make it pest-resistant. Introducing Bt technology in crops where pesticide use is high, yields spin-off benefits for soil and water contamination, said Mr. B. Sesikeran, a member of the Review Committee on Genetic Modification. Critics of GM crops say that there could be serious health risks and the pros and cons must be publicly debated because this is a one-way road and at least 33 GM food crops including rice, okra and potato are in the pipeline.

Malladi Drugs & Pharmaceuticals Ltd. (Malladi Drugs), an API manufacturer based in Chennai, is committed to invest up to US$300 million in the next 3-5 years with aims to expand into other areas of service offering as a contract research organization in Malaysia. This includes oncology and steroids and beta-lactums. Malladis activities will turn Malaysia into an outsourcing centre for pharmaceutical companies from the United States and Europe.


A US$60 million HIV/TB research initiative launched

Scientists from Howard Hughes Medical Institute (HHMI), the United States, and the University of KwaZulu Natal (UKZN), South Africa, recently announced the launch of a US$60 million, 10-year initiative to establish a new research centre to examine the associations between tuberculosis (TB) and HIV. HHMI will finance the project and US$20 million will be used to establish a research institute on the Durban campus of UKZNs Nelson Mandela Medical School, which will include two floors of high-level biosafety laboratories. The remaining amount will fund research, training and related programmes over a 10-year period.

Scientists involved with the project will study the increasing incidence of HIV/TB co-infection and examine outbreaks of extensively drug-resistant TB among HIV-positive people. Dr. Salim Abdool Karim, Director of the Centre for AIDS Programme of Research in South Africa, said the scientists will also study the causes of recurrent TB and the spread of TB among HIV-positive people in health centre waiting rooms. The challenges of diagnosing TB among HIV-positive people will be examined and the genetic factors that could contribute to drug resistance will be analysed. HIV immunology and the role HIV plays in the development of aggressive TB will also be studied.


Life science research in economic recession

Scientists engaged in biological research and drug discovery are bracing for expected cuts in their 2009 laboratory budgets. BioInformatics LLC has released preliminary data from its newest report, Prospering in a Down Market: Strategies for Life Science Suppliers.

In response to requests from the life science supply industry, BioInformatics LLC conducted a survey among more than 500 senior scientists and lab managers working in universities, and pharmaceutical and biotechnology companies. Nearly half of respondents surveyed said they are very worried that a recession will make it difficult for them to conduct their research and close to two-thirds said that their research has already been affected by the current economic recession. According to Dr. Tamara Zemlo, Vice President of Advisory Services of BioInformatics LLC, life sciences will likely fare better than other sectors of the economy.



Bharat Biotech launches pentavalent combination vaccine

Bharat Biotech International Ltd. (BBIL), a leading producer of vaccines and biotherapeutics in India, has launched COMVAC5, a single-shot pentavalent combination vaccine against diphtheria, pertussis, tetanus, hepatitis B and haemophilus influenza type b (Hib). BBILs vaccine is claimed to be the first fully indegenous single-shot pentavalent combination vaccine. COMVAC5 is said to be safe, efficacious and affordable, and to offer complete protection against Hib antigen bacterium that causes severe pneumonia as well as meningitis in children.


Akron Biotechnology merging with AppliChem

AppliChem GmbH, Germany, and Akron Biotech, the United States, are combining forces for the manufacture and distribution of both companies products. From March 2009, Akron Biotech will take over AppliChem operations in the Americas and will be called AppliChem LLC. AppliChem LLC will offer its customers high-quality products including animal serum, recombinant proteins, serum-free media and other cell-culture components in addition to AppliChem GmbHs 4,000 products. The merger with AppliChem GmbH will allow us to expand our product offering dramatically, and will accelerate our companys growth, said Akron Biotechs CEO, Dr. Claudia Zylberberg, who will continue to operate as the CEO and President of AppliChem LLC.


GE to expand global R&D capabilities

GE Global Research, the technology development arm of General Electric Company based in the United States, has announced the opening of its newest research space at its dedicated technology campus in Bangalore, India. The new environmentally designed facility will house nearly 2,000 researchers.

Since 2001, GE has made capital investments totalling US$330 million to expand its global research facilities, including large investments in its headquarters in New York, the addition of a new centre in Munich, Germany and further expansion of its research operations in Shanghai, China. GE researchers have filed more than 2,500 patents in 2008 alone.

The growth in India complements the strong growth at the companys Global Research centre in the United States in recent years. Over the last seven years, GEs annual R&D expenditure has nearly doubled from US$2.3 billion to US$4.3 billion. The funding has been directed towards new technologies that are the cornerstone of GEs future growth plans, including power generation, biosciences, renewable energy and healthcare.


Lifecell launches R&D centre

In India, LifeCell International, a leader in stem cell banking, has established its R&D centre in Chennai for development of stem cell technologies. The facility would focus on increasing the gamut of stem cell banking of developing process for isolation, processing and preservation of other stem cell rich tissues in the body.

The R&D facility set up by LifeCell is a first of its kind research centre in India devoted exclusively for stem cells, stated Mr. Mayur Abhaya, Executive Director of LifeCell International. Dr. Ajit Kumar, Chief Scientific Officer of LifeCell International, will lead the operations with a team of 15 scientific and medical professionals.


Lab21 acquires Biotec Laboratories

In United Kingdom, Lab21 Ltd., a global provider of state-of-the-art diagnostic products and services, has purchased the majority shareholding of Biotec Laboratories Ltd. (BLL), a clinical diagnostic company with particular emphasis on infectious diseases, most notably tuberculosis (TB). As part of the sale, Lab21 also acquires Biotec Laboratories S.A., BLLs South African subsidiary. The financial terms of the deal were not disclosed.

The two companies have had an ongoing commercial relationship, with BLL distributing some of Lab21 diagnostic products through its global network of distributors in 80 countries worldwide. Biotec Laboratories S.A., based in Johannesburg, has developed proprietary phage amplification technology that is being used to develop rapid diagnostic and susceptibility tests for both active and drug-resistant TB.



StemCells Inc. to acquire cell-based drug discovery platforms

In the United States, Stem Cell Sciences plc (SCS) has entered into an agreement with StemCells Inc. (SCI) for the sale of the trading subsidiaries of the company and certain ancillary agreements, assets, properties and rights for a maximum total consideration of about US$4,8 million. SCI will acquire the operating subsidiaries and certain related assets of SCS for 2,650,000 shares of SCI common stock and approximately US$715,000 of waived loan entitlements.

The transaction is subject to customary closing conditions, including the approval of the shareholders of SCS in general meeting. Members of the SCS Board and other significant stockholders representing over 30 per cent of the SCS shares outstanding have irrevocably agreed to vote in favor of the transaction.


Partnership to promote enhanced vaccine development

A new international partnership between the biotechnology firm ImmunoVaccine Technologies (IVT) of Canada and the National Institute of Allergy and Infectious Diseases (NIAID) of the United States aims at enhanced vaccine development especially for pandemic diseases such as AIDS and malaria.

IVT will be using its patented DepoVax vaccine enhancement system to produce vaccines based on disease antigens prepared at NIAID. Protein antigens from the AIDS virus and the malaria parasite will be the first targets for vaccine development in the new programme. The ultimate objective is to produce immunostimulatory agents that will be able to induce antibody and T cell responses.




Discovery of new retinal gene involved in childhood blindness

In Canada, a team of scientists led by Dr. Robert Koenekoop at the Research Institute of the McGill University Health Centre has played a crucial role in the international collaboration that led to the discovery of a new gene that causes Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP), two devastating forms of juvenile blindness. The finding of this new gene, called SPATA7, is remarkable because it identifies a new retinal metabolic disease pathway that may be crucial for many patients. It also opens a new avenue for a potential genetic therapy.

Researchers have now identified LCA 15 genes, but SPATA7 is the first gene with a mutation that disrupts the protein transport between two important compartments of the cell: the endoplasmic reticulum and the Golgi apparatus. All proteins in every cell have to pass through this transport pathway; thus, SPATA7 plays a major role and its mutation may affect many aspects of vision.
SPATA7 was identified using a technology developed in the different laboratories involved in this international collaboration. The novel technique is based on DNA-chips and involves three steps. First, the patients genetic material is screened to find mutations in 14 specific LCA and RP genes. The LCA and RP patients that are negative for this detailed screen are then subjected to a second DNA chip, this one to identify significant stretches of homozygosity in single nucleotide polymorphism (SNP) markers. SNPs are natural variations in the human genome.


Gene involved in pancreatic cancer identified

In the United States, a team of researchers from the University of Michigan Comprehensive Cancer Centre, M.D. Anderson Cancer Centre and Mayo Clinic, has identified a gene over-expressed in 90 per cent of pancreatic cancers, the most deadly type of cancer. Expression of the gene, called Ataxia Telangiectasia Group D Complementing gene (ATDC), is on average 20 times higher in pancreatic cancer cells than in cells from a normal pancreas.

We found that ATDC not only causes the cancer cells to grow faster and be more aggressive, but it also makes the cancer cells resistant to chemotherapy and radiation. By targeting this gene, we may be able to make cancer cells more sensitive to the therapies we already have in hand, says Dr. Diane Simeone, senior author of the study. The researchers injected mice with tumour cells expressing ATDC and compared them with another group of mice injected with tumour cells in which ATDC was suppressed. In the ATDC-expressing group, tumours grew in all the samples and were significantly larger and starting to metastasize. In the group in which ATDC was not expressed, only minimal signs of tumour growth were seen after 60 days. In addition, the researchers found that ATDC was most highly expressed at the point when pre-cancerous cells had become malignant. ATDC is also linked to increased levels of a signalling protein, beta-catenin, which is known to play a key role in cancer development.


How yeast is helping us to understand Parkinsons disease

Teams of scientists from Australia and the United States have used yeast and mammalian cells to discover a connection between genetic and environmental causes of Parkinsons disease. Two genes (alpha-synuclein and PARK9) had separately been associated with forms of Parkinsons disease, while manganese poisoning can cause PD-like symptoms in miners and welders exposed to high manganese levels. Now, yeast research has found connections between alpha-synuclein, PARK9 and sensitivity to manganese.

Parkinsons disease involves the degeneration of neurones that produce the neurotransmitter dopamine. Autopsies show an abundance of the small protein alpha-synuclein in affected regions of the brain. A European group discovered PARK9s involvement in an inherited form of Parkinsons disease and examined some of the surviving neurones from patients who had sporadic, as opposed to inherited, form of Parkinsons disease. The neurones were found to contain ten times the levels of PARK9, as compared with similar parts of the brain in patients without the disease.

It is possible that the surviving neurones remained functional, unlike the degenerated neurones surrounding them, because high levels of PARK9 protected them in some way, said Dr. Antony Cooper from Sydneys Garvan Institute of Medical Research and head of the project group in Australia. Although little was known of PARK9s function, as yeast contains an equivalent gene, the researchers were able to analyse its function. We found that high levels of the PARK9 in a cell diminish the toxic effects of alpha-synuclein. We also found that it appears to be a manganese pump, capable in theory of removing excess levels of the metal from cells, revealed Dr. Cooper. He believes that the linkages between PARK9, alpha-synuclein and manganese toxicity are not coincidental, and would like to find whether a central pathway is involved. Such a pathway would provide much better potential for finding a successful treatment.


New genetic link to high levels of good cholesterol

HDL cholesterol (HDL-C), or good cholesterol, carries excess cholesterol from blood vessels back to the liver for processing and elimination, thus preventing blockage of arteries. Hence, individuals with high plasma HDL-C levels have less risk of developing coronary artery disease. A new study by Dr. Daniel Rader and colleagues from the University of Pennsylvania, the United States, show that mutations in the LIPG gene, which codes for the enzyme endothelial lipase, result in high plasma HDL-C levels.

The scientists examined the LIPG gene in 585 subjects of European ancestry and identified 10 people with previously unreported rare mutated forms of this gene that were unique to subjects with very high HDL-C levels. They found that LIPG gene mutations that cause loss of endothelial lipase activity were the cause of increased plasma HDL-C levels. These data provide key human genetic evidence that endothelial lipase inhibition might raise HDL-C levels. Further study is needed to find whether the increase in HDL-C level due to this inhibition would impact cardiovascular health.


Smokers COPD risk is genetic

IWhy do only a quarter of long-term smokers develop serious breathing problems, when others do not? New research has found that the key to this may lie in a smokers genetics, which affect their chances of developing chronic obstructive pulmonary disease (COPD) in later life. In the United States, Dr. Alireza Sadeghnejad and colleagues from the Wake Forest University School of Medicine and Saint Louis University looked at a disintegrin and metalloprotease (ADAM) gene, called ADAM33, in 880 long-term heavy smokers. Located on chromosome 20, ADAM33 has been linked with asthma in previous studies.

The researchers found five single nucleotide polymorphisms (SNPs) variations in human DNA sequence in ADAM33 that were more frequent in the COPD group than in the group of smokers without COPD. One SNP, known as S1, had a particularly strong linkage to lung abnormalities. Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD, according to the scientists.


Schizophrenia-linked gene controls neuron birth

A schizophrenia gene plays an unanticipated role in the brain: it controls the birth of new neurons in addition to their integration into existing brain circuitry, according to a recent study in the United States by scientists from Howard Hughes Medical Institute (HHMI), Massachusetts Institute of Technology and Massachusetts General Hospital. The finding suggests that loss of the gene, as occurs in some cases of schizophrenia as well as bipolar disorder and major depression, may tip the balance in the brain, leading to an increased risk of compromised cognition and behavioural abnormalities, the researchers said.

In addition, the protein encoded by the gene aptly known as Disrupted in Schizophrenia 1 (DISC1) exerts its influence through a well-studied molecular pathway. It interacts directly with and blocks the activity of GSK3b, a protein target of lithium treatments that doctors have used for decades in bipolar disorders. This shows that DISC1 is almost like an endogenous lithium, said Dr. Li Huei Tsai from HHMI. Although people diagnosed with schizophrenia are typically resistant to lithium treatment, she added, their findings should encourage scientists to think creatively about new and more powerful strategies for targeting GSK3b.

DISC1 is among the many risk genes associated with schizophrenia that recent studies have identified. Biochemical evidence has shown DISC1 as interacting with a growing number of binding partners, Tsai said, and functional studies have revealed a role for the gene in the growth and migration of neurons and in their integration into the brain. Dr. Tsais team has begun to connect the genetic and biochemical evidence with behaviour in mouse studies.

DISC1 is also highly expressed in neural progenitor cells and is required for their proliferation. This function of DISC1 involves regulation of the b-catenin/GSK3b pathway. In the adult mouse brain, loss of DISC1 function led to reduced neural progenitor proliferation and elicited hyperactive and depressive behaviours in mice. Importantly, the behavioural abnormalities were reversed when the DISC1-deficient animals were treated with a chemical that blocked GSK3b, prompting the researchers to conclude that DISC1 is a key player in the GSK3b/b-catenin signalling pathway that impinges on neural progenitor proliferation.



New study reveals genetic link to blood cancers

The recent study has shown that susceptibility to a series of blood cancers, known as myeloproliferative disorders (MPDs), is linked to a particular area of the patients DNA, which is prone to developing mutations. The research carried out in the United Kingdom, at the Wessex Regional Genetics Laboratory and the University of Southampton, found that a specific region of chromosome 9 that carries the gene, called JAK2, is predisposed to acquiring mutations but only in individuals with a particular genetic make-up.

MPDs are characterized by the overproduction of red and white blood cells, which increases the risk of strokes and heart attacks. Many cases of MPDs are caused by a mutation in JAK2. When the JAK2 gene has mutated, it sends abnormal messages to the blood stem cells to produce more and more blood cells. The study has proved that people carrying this mutation-prone region of DNA on chromosome 9 have three times the risk of developing an MPD.

The link was found to be especially strong in polycythaemia vera (PV), one of the main three MPDs. Professor Nick Cross, from the University of Southampton, who led the researchers, says: This research provides strong evidence that at least half of the cases of PV diagnosed each year are linked to an inherited genetic variant on chromosome 9..


Genetic discovery could lead to advances in dental treatment

In the United States, Oregon State University (OSU) researchers have identified the gene that ultimately controls the production of tooth enamel a significant advance that could some day lead to the repair of damaged enamel, a new concept in cavity prevention and restoration or even the production of replacement teeth. The Ctip2 gene is a transcription factor known to have several functions in immune response, and the development of skin and the nervous system.

This is the first transcription factor ever found to control the formation and maturation of ameloblasts, which are the cells that secrete enamel, said Dr. Chrissa Kioussi, an assistant professor in the OSU College of Pharmacy. The scientists used a laboratory mouse model in this study in which Ctip2 gene has been knocked out and its protein is missing. The mice had rudimentary teeth ready to erupt, but they lacked a proper enamel coating, one of the hardest natural coatings that evolved to give carnivores the tough and long-lasting teeth they needed to survive.

With an understanding of the genetic underpinning of enamel coating, Dr. Kioussi said, it may be possible to use tooth stem cells to stimulate the growth of new enamel. Some groups had succeeded in growing the inner portions of teeth in laboratory animal experiments, but those teeth have no hard coatings as the genetic material that makes the enamel was lacking.



Protein helps immune cells to divide and conquer

The rapid generation of large numbers of B lymphocytes is critical to the bodys antibody defence mechanism. When B cells grow unchecked, however, it can lead to immune cell cancers such as multiple myeloma or, when they grow to attack the wrong targets, to autoimmune disease. At the University of California-San Diego (UCSD), the United States, researchers have identified a key protein that is required for B lymphocytes to replicate themselves. By discovering the role of the CD98hc protein, scientists may find new therapy targets for such diseases.

The research from the laboratory of Dr. Mark H. Ginsberg, professor of medicine at UCSD School of Medicine, describes why CD98hc is essential in order for B lymphocytes to transition into antibody-secreting cells. It also describes how this relates to the proteins role in the signalling ability of integrins a large family of adhesion molecules that transfer information between the inside and outside of a cell.

The scientists created a mouse model lacking the CD98hc protein in B lymphocytes. When vaccinated, these mice were unable to mount a normal antibody response to the pathogen. This proved that the protein was essential to expanding the number of immune cells, a necessary step in the immune response. Deletion of the protein also inhibited later activation of elements along the signalling pathway that push the cell forward to divide. By replacing normal CD98hc in B cells with a version that lacked one or the other of these two functions, the scientists found that the integrin-binding domain of this protein is required, but the amino acid transport function is dispensable for B cell proliferation.


Biologists discover a protein link to wound healing

Scientists at the University of California-San Diego (UCSD), the United States, have reported that a protein previously linked only to cell death, plays a critical role in the healing of wounds in laboratory mice. This protein, known as caspase 8, is deficient in humans with eczema, but produced in excess amounts by diabetics. The researchers say their discovery may explain why many diabetics lack a normal wound response and suffer complications from minor cuts and scrapes, and why those with eczema exhibit a chronic inflammation of the skin that compromises its protective function.

The discovery occurred by accident when Dr. Colin Jamora, a UCSD assistant professor and head of the research team, was asked by a colleague Dr. Steve Hedrick to examine a genetically engineered mutant mouse with unusually thick skin. Dr. Hedricks team had knocked out the gene in the epidermis necessary for caspase 8 production. Dr. Jamora initially suspected that the lack of caspase 8 in the epidermis was interfering with the apoptosis of the skin cells, leading to an accumulation of skin cells that should have otherwise died. Instead, he found that the lack of caspase 8 was stimulating more skin cells to divide. The scientists also found that the skin of these mice was inflamed. Those two things led them to suspect that the loss of caspase 8 can trigger a normal wound healing response in the absence of any trauma to the skin.

However, caspase 8 resides in cells at the surface of the epidermis, while stem cells responsible for the proliferation phase were deeper in the tissue and the infection-fighting cells in the blood vessels responsible for the inflammation phase were deeper still. Investigation of this anomaly revealed that the loss of caspase 8 in the epidermis releases a cell protein called interleukin 1-alpha that can travel deeper into the tissue to recruit immune cells and cause the local reservoirs of stem cells in the skin to start proliferating. This protein is a known stimulator of inflammatory response, but this is the first time anyone has demonstrated that caspase 8 triggers the release of this protein.


Sperm-binding proteins cloned

Scientists at Canadas Universit de Montral and its affiliate Maisonneuve-Rosemont Hospital Research Centre have become the first to clone, produce and purify Binder of Sperm (BSP), a protein important for sperm maturation. The development may have implications for both fertility treatments and male contraception.

We have previously isolated and characterized BSPs from many species, such as bulls and boars, says Dr. Puttaswamy Manjunath, senior author and a professor at the Universit de Montral and a member of Maisonneuve-Rosemont Hospital Research Centre. We know from these studies that if this protein is missing or defective in these species, fertility is compromised. We believe BSP is equally important in humans.

According to the researchers, humans, primates and rodents produce small amounts of BSPs only in the epididymis, a duct that connects the testes to the urethra, not in the seminal vesicles like most mammals. They cloned the DNA that encodes human BSP and through cloning, they were able to produce and purify this protein. A family of BSPs secreted by the seminal vesicles has been shown to be essential for sperm maturation in female reproductive tracts of pigs, cows, sheep and other such hoofed animals.


Antibody-protein binding key to treating variant CJD

In the United Kingdom, scientists at the University of Liverpool (UL) and Medical Research Council Prion Unit (MRC-PU), University College London, have determined the atomic structure of the binding between a brain protein and an antibody that could be key to treating diseases such as variant Creutzfeldt-Jakob Disease (vCJD).

Part of a family of rare progressive neurodegenerative disorders called prion diseases, vCJD affects both animals and humans. Prion diseases can develop when a naturally occurring brain prion protein called, PrP, is exposed to infectious prions. This converts PrP into a form that has a different shape, and eventually leads to a build-up of protein in the brain, causing brain cells to die. It is thought that immunization with antibodies that can stick to PrP could treat and even prevent the development of the disease.

To understand the connection between the antibody and the protein, the scientists used X-ray crystallography to build a 3-D picture of the binding between an antibody called ICSM18 designed to adhere effectively to prion proteins and PrP cells. Dr. Samar Hasnain, a UL professor of molecular biophysics, said that the point at which the protein and antibody came together was also where scientists at the MRC-PU had identified a single amino acid, denoting a significant impact on a patients susceptibility to prion disease. Scientists at the MRC-PU have found that ICSM18 could help prevent brain cells from becoming infected as well as reverse early damage caused by the disease.


Protein protects bacteria from digestive acids

A tiny protein helps protect disease-causing bacteria from the ravaging effects of stomach acid. This discovery was made in the United States by researchers at the University of Michigan (UM) and Howard Hughes Medical Institute (HHMI). Stomach acid aids in food digestion and helps kill disease-causing bacteria.

One way that acid kills bacteria is by causing the proteins in them to unfold and stick together in much the same way that heating an egg causes its proteins to form a solid mass. Just as it is virtually impossible for a cook to unboil an egg, it is also difficult for bacteria to dissolve these protein clumps. Hence, bacteria and most living things can die when exposed to acid or heat. However, disease-causing bacteria such as E. coli are protected from stomach acid by a tiny protein called HdeA, report Dr. James Bardwell, a UM professor and HHMI investigator, and his co-researchers.

Like other proteins, HdeA unfolds and becomes more flexible when exposed to acid. But in a clever twist, instead of inactivating, the unfolding process activates HdeA. Once unfolded, this plastic protein moulds itself to fit other bacterial proteins that have been made sticky by acid-induced unfolding. Just as plastic wrappers prevent candies from sticking together, HdeA prevents the unfolded proteins from sticking together and forming clumps, said Dr. Bardwell. HdeA directly senses acid and changes from its inactive to active form within a fraction of a second, added Dr. Tim Tapley, a UM post-doctoral fellow who spearheaded the research.

Instead of becoming completely unfolded in response to acid and sticking to itself, HdeA is only partially unfolded. It then uses the flexibility gained through partial unfolding to rapidly become plastic enough to adapt to and bind various damaged proteins. This helps bacteria like E. coli evade the otherwise deadly effects of stomach acid.


Bioengineered proteins: a new way to tackle cancer

Re-engineering a protein that helps prevent growth and spreading of tumours has created a potentially powerful therapy for many different types of cancer. Scientists from the University of Toronto, Canada, modified the tumour-inhibiting protein, von Hippel-Lindau (VHL), and demonstrated that it could suppress tumour growth in mice.

When solid tumours grow, they often have relatively poor and disorganized blood supplies. As a result, various regions including the centre of the tumour are hypoxic, or have low levels of oxygen. Cells in these hypoxic areas produce hypoxia-inducible factor (HIF) that helps them carry on growing. Consequently, HIF is associated with aggressiveness in some of the most common types of cancer, including prostate, breast, colon and lung cancer. Under normal conditions, VHL degrades HIF; however, VHL is deactivated when oxygen levels are low. So, in hypoxic regions of a tumour, just where VHL is needed to inhibit cancer, it is ineffective. The researchers created a new version of VHL that does not stop working when oxygen is scarce. Introducing this newly engineered version of VHL into mice that had kidney tumours showed dramatic reduction in the levels of HIF, caused tumours to regress and limited the formation of new blood vessels within the tumours.

We have genetically removed the Achilles heel of VHL to permit unrestricted destruction of HIF, stated lead researcher Professor Michael Ohh. The level of HIF is usually very high under conditions of low oxygen, but when we put in our bio-engineered VHL its levels go right down to a level that would be comparable to that in normal oxygen levels. The findings could have implications for any type of cancer in which HIF plays a role.

There were major differences too. For instance, when helices of natural peptides nestle against one another, often their side chains extend from the sides of each helix, fitting together like ridges in grooves. The beta-peptide helices, however, are structured so that their side chains alternate like interlocking fingers.




Blood test predicts chance of dementia

In Belgium, the researchers from Flanders Institute for Biotechnology (VIB) connected to the Born-Bunge Institute and the University of Antwerp have discovered that the amount of growth factor progranulin in blood is a predictor of fronto-temporal dementia (FTD). Progranulin plays a major role in the survival of brain cells, and those who have less progranulin carry higher risk of contracting FTD. The researchers developed an early detection test that measures the amount of progranulin in the blood to predict a persons risk.

After Alzheimers disease, FTD is the form of dementia that occurs most frequently in patients younger than 65. In FTD, the disease process starts in the frontal lobe where large numbers of brain cells begin to die off. So, the first clinical signs of FTD are changes in behaviour and personality, and then, in a later stage of the disease, the loss of memory functions. Genetic research had shown that a genetic defect in two genes, one for tau protein and the other for progranulin protein, in chromosome 17 cause a hereditable form of FTD. New results indicate that progranulin also plays a role in the death of brain cells in other diseases of the brain, such as Alzheimers disease and amyotrophic lateral sclerosis (ALS).

Based on those studies, Dr. Kristel Sleegers and colleagues have developed a test for measuring the quantity of progranulin in the blood in a simple way. This test enables one to determine whether someone has an increased risk of FTD due to a shortage of progranulin long before symptoms appear. The blood test can be used on a large scale and is reported to be much more simple and user-friendly than the current genetic tests.



A natural approach to HIV vaccine development

Scientists at the Rockefeller University, the United States, have laid out a new approach to tackle HIV. They have identified a diverse group of antibodies in slow-progressing HIV patients whose co-ordinated pack hunting knocks down the virus just as well as their super-antibody cousins. Citing the dynamic, natural immune response in these exceptional patients, Dr. Michel C. Nussenzweig, who heads the Laboratory of Molecular Immunology, and colleagues suggest that an effective HIV vaccine may come from a shotgun approach using of a wide range of natural antibodies rather than an engineered magic bullet. While the many different antibodies in those patients individually have limited neutralizing abilities, together they are quite powerful, says Dr. Nussenzweig.

Almost all diverging strains of HIV have a protein called gp140 on the envelope of the virus that it needs to infect immune cells. Prior research has shown that four randomly engineered antibodies that block the activity of that protein prevent the virus from infecting immune cells in culture, but all attempts to coax the human body into producing those four have failed.

Mr. Johannes Scheid, a doctoral candidate at Dr. Nussenzweigs laboratory, turned his attention to the antibodies produced by six people infected with HIV whose immune systems put up an exceptionally strong fight. Along with his colleagues, he isolated 433 antibodies from these patients blood serum that specifically targeted the envelope protein, the chink in HIVs protean armour. Mr. Scheid cloned the antibodies and produced them in bulk, mapped which part of the envelope protein each targeted, and gauged how effective each was in neutralizing the virus. In the process, he identified a new structure within the envelope protein called the gp120 core that had never been recognized as a potential target for antibodies.



Study suggests blood test for Alzheimers possible

In the United States, researchers from the University of Georgia, the Charlie Norwood VA Medical Centre and the Medical College of Georgia have found direct relationship between two specific antibodies and the severity of Alzheimers disease symptoms, raising hopes that a diagnostic blood test for the devastating disorder is within reach. The team compared antibody levels in blood samples from 118 older dementia patients, and found that the concentration of two specific proteins that are involved in immune responses increases with the severity of dementia.

The team focused on antibodies that the body creates in response to two proteins that are associated with Alzheimers disease. One protein, amyloid-beta, forms plaques in the brains of people with Alzheimers disease. The other protein, RAGE, is involved in the normal aging process, but is expressed at higher levels in the brains of people with Alzheimers disease.

The researchers are targeting the two proteins as a possible treatment for Alzheimers disease. They recently developed a way to measure levels of amyloid beta-RAGE complex, and preliminary data using transgenic mice that express Alzheimers symptoms suggest that an antigen they created to boost the bodys natural immune response to the complex can reduce the formation of the brain plaques.



Scientists find new drug target on bird flu virus

French and Chinese scientists have discovered the intricate structure of an important component of the H5N1 virus a move they hope will provide a new approach for developing antiviral drugs. Two papers published in Nature describe the structure of a part of RNA polymerase, an important H5N1 virus enzyme that is responsible for virus replication in host cells.

Both studies use a technique called X-ray crystallography to determine the exact structure of a section of the enzyme called PA. This section could be an important target for new drugs as the inhibition of PAs activity will stop the virus from replicating. Before these studies, it was difficult to find an effective way of inhibiting the H5N1 virus because it mutates so rapidly.

Dr. Stephen Cusack, a senior scientist at the European Molecular Biology Laboratory and lead researcher of the French team, said that knowing the structure of PA will make it easier to find and improve agents to inhibit the region. The resulting drugs would target a region on PA that doesnt mutate fast, say the Chinese researchers, led by Dr. Rao Zihe of the Laboratory of Structural Biology at Tsinghua University.


Approval for first DNA test for human papillomavirus

The United States Food and Drug Administration (FDA) has approved the first DNA test, which identifies the two types of human papillomavirus (HPV) that cause a majority of cervical cancers among women. The test, called Cervista HPV 16/18, detects the DNA sequences for HPV type 16 and HPV type 18 in cervical cells. Differentiating these HPV types yields more information on a patients risk of developing cervical cancer. A positive Cervista 16/18 test result will show whether HPV type 16, 18 or both are present in the cervical sample.

FDA also approved the Cervista HPV HR test, which is the second DNA test that detects essentially all of the high-risk HPV types in cervical cell samples. The Cervista HPV HR test uses a method similar to the Cervista HPV 16/18 test to detect the DNA sequences of these HPV types. Both Cervista HPV 16/18 and Cervista HPV HR are manufactured by Third Wave Technologies, the United States.



Tuberculosis vaccine developed

McMaster University researchers are about to launch Canadas first clinical trial of a tuberculosis (TB) vaccine, totally designed, manufactured and tested within McMaster. Development of the vaccine for the trial was led by Dr. Zhou Xing from the Department of Pathology and Molecular Medicine. The vaccine was manufactured in the Robert E. Fitzhenry Vector Laboratory of the Institute of Molecular Medicine and Health. Most of the pre-clinical testing of the vaccine was carried out at McMaster.

Over 12-18 months, the researchers will evaluate the safety of the new vaccine (called AdAg85A vaccine) and assess blood samples from vaccinated healthy human volunteers to determine if the vaccine is generating a desired immune response. The new TB vaccine was developed using a genetically modified adenovirus. After removing a small portion of the gene, they inserted part of the TB gene responsible for immunity. The pre-clinical studies of the candidate vaccine carried out on animals including mice, guinea pigs and cattle have been very promising, said Prof. Xing.



Gene to reduce wheat yield losses

Scientists have discovered a new gene that provides resistance to a fungal disease responsible for millions of hectares of lost wheat yield. This is the first step to achieving more durable resistance to a devastating disease in wheat, said Dr. Cristobal Uauy from University of Haifa, Israel, one of the authors of the report. Other scientists involved in the study were from the United States, from the University of California-Davis, Department of Agricultures Agricultural Research Service and Washington State University.

Resistance to stripe rust has previously been achieved using genes that are specific to single races of the disease. Unfortunately, each of these genes has had limited durability in the field because the pathogen mutated to overcome them. The new study focused on finding a novel type of gene Yr36 (WKS1) in wild wheat that is absent in bread and pasta wheat varieties. This gene makes wheat more resistant to all stripe rust fungus races tested so far, said Dr. Uauy. The gene confers resistance at relatively high temperatures.

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Vegetal drugs may target melanoma tumours

A drug based on compounds extracted from cruciferous vegetables, such as broccoli and cabbage, could offer a potent and safe treatment against melanoma, say scientists at Penn State University College of Medicine, the United States. In mice, a combination of these vegetable compounds, called isothiocyanates, and selenium slowed the production and blocked the signalling network of a protein called Akt3 which plays a role in melanoma development and reduced tumour growth by 60 per cent.

There are currently no drugs to target the proteins that trigger melanoma. We have developed drugs from naturally occurring compounds that can inhibit the growth of tumours in mice by 50 to 60 per cent with a very low dose, said Dr. Gavin Robertson, an associate professor of pharmacology, pathology and dermatology. The potency of isothiocyanates is so low that a useful drug would require impractically large amounts of the compounds. Instead, the researchers altered the vegetable-based compounds by replacing their sulphur bonds with selenium, resulting in a more powerful drug that can be delivered intravenously at low doses. The new drug, called isoselenocyanate, is more advantageous because selenium deficiency is common in cancer patients. Selenium is also known to destabilize Akt proteins in prostate cancer cells. The combination drug was found 30-70 per cent effective on different human melanoma cell lines.



Rust resistance genes in soybeans identified

A team of researchers from the United States Department of Agricultures Agricultural Research Service (ARS) and Iowa State University, and the Brazilian Agricultural Research Corporation have identified a cluster of soybean genes that provide resistance to the fungus Phakopsora pachyrhizi, which causes Asian soybean rust (ASR).

Genetic mapping previously linked ASR resistance to five DNA regions, or loci, within the soybean genome, named Rpp1 through Rpp5. Screening of 15,000 accessions in the ARS soybean germplasm collection revealed how rare the resistance is: less than 5 per cent. The researchers sequenced Rpp4 locus and identified a cluster of candidate genes that confer ASR resistance. Comparisons of susceptible and resistant cultivars identified Rpp4C4, a candidate gene thought to bestow resistance.

Rpp4C4 is one of five nearly identical genes in Rpp4 locus. Frequent recombination within the cluster allowed the formation of new disease resistance genes. Soybean cultivar Williams82, for example, has three resistance genes in the cluster and lacks Rpp4C4, making it vulnerable to ASR. However, the source of Rpp4 resistance, line PI459025B, has five candidate genes. Virus-induced gene silencing studies were used to turn off the Rpp4 candidate genes in PI459025B, making it susceptible to ASR and confirming the genes importance.



Diabetes drug grown in tobacco plants

European scientists have found a healthy use for tobacco after breeding genetically modified plants containing a medicine that could stop type 1 diabetes. Researchers said that they had produced tobacco plants containing interleukin-10 (IL-10), a potent anti-inflammatory protein, that could help patients with insulin-dependent type 1 diabetes and other autoimmune diseases.

Dr. Mario Pezzotti of the University of Verona, Italy, who led the tobacco study, believes such drugs could be grown more efficiently in fields, since plants are the worlds most cost-effective protein producers. Several different plants have been studied by research groups around the world, but tobacco is a firm favourite. Tobacco is a fantastic plant because it is easy to transform genetically and you can easily regenerate an entire plant from a single cell, Dr. Pezzotti said.

Dr. Pezzotti and colleagues now plan to feed the plants to mice with autoimmune diseases to find out how they respond. Further down the line, they want to test whether repeated small doses could help prevent diabetes in people, when given with another compound called glutamic acid decarboxylase (GAD65), which has also been produced in tobacco plants.



New protein-rich pea hybrid

The International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), based in India, has developed a new, improved protein-rich pea that promises 40 per cent higher yields. Pushkal, the new variety of pigeon pea, is the first commercially available hybrid legume in the world.

With 40 per cent higher yields than the best local varieties, Pushkal is truly the magic pea, William Dar, ICRISATs Director General, said in a report. The new hybrid thrives in drought conditions and has greater resistance to diseases. It also creates a strong root system that aids greater nitrogen fixation to keep soils fertile.

The scientists developed Pushkal (ICPH 2671) using a new breeding technology Cytoplasmic Male Sterility (CMS) and natural out-crossing to develop hybrid. The process requires female plant in which no viable pollen grains are born. Under CMS protocol, male organs (anthers) are removed from the plants to develop a male sterile line. This male-sterile line is, therefore, unable to self-pollinate and seed formation is dependent on pollen from the male fertile line. By developing a parental line that has the trait of male-sterility in the cytoplasm, it was ensured that all progeny from this line were male-sterile, the report said.


GM work boosts apple disease resistance

In the Netherlands, apples are being genetically modified to make them resistant to scab and other diseases. Cisgenesis, the technique being used, would be more acceptable to consumers and environmentalists because the resistance genes used come from wild apple species rather than a foreign source.

Conventional breeding and commercial production of good-quality scab-resistant varieties takes as long as 50 years, explains Dr. Henk Schouten of Plant Research International, based at Wageningen University. The trouble is that only one resistance gene is involved and in Holland, this resistance has broken down within 10 years of the resistant variety being introduced. The main advantages of cisgenesis are that: it is a much quicker process; several resistant genes can be used, making the breakdown of resistance difficult; and the genes are inserted into the genomes of good-quality, established varieties. Furthermore, as the technique takes only seven years, cisgenesis would be cheaper than the conventional approach.

Science now knows how to isolate genes (for resistance) and introduce them into the DNA of existing varieties, said Dr. Schouten. Once we have got the right gene in our hands, it will cost about 500,000 to get it into a variety.



Discovery of bilirubin in plants

In a discovery that overturns conventional wisdom, researchers at the Florida International University, the United States, have reported that certain plants make bilirubin. Until now, scientists thought that bilirubin existed only in animals. The finding may change scientific understanding of how the ability to make bilirubin evolved.

In the new study, Dr. Cary Pirone and colleagues note that bilirubin is a brownish yellow substance resulting from the livers breakdown of haeme, found in haemoglobin, the red pigment that carries oxygen in the blood. Bilirubin is the stuff that gives a yellowish tinge to the skin of patients with jaundice. Until now, scientists never dreamed that plants too produce bilirubin.
The researchers used two powerful laboratory techniques, liquid chromatography and nuclear magnetic resonance, to isolate bilirubin from the brilliant orange-coloured arils of the fruit of white bird of paradise tree (Strelitzia nicolai). They also found the pigment in two closely related plant species, including S. reginae, the bird of paradise.


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Altered tobacco plant may produce anti-HIV microbicide gel

A new study has shown that transgenic versions of a plant Nicotiana benthamiana may be able to produce large quantities of a protein griffithsin, which can be used as a microbicide gel to contain spread of HIV through sexual intercourse. The protein has shown capabilities of neutralizing HIV, as it binds to the virus molecule in such a way that the virus could not disguise itself from the immune system of humans. The technique would allow scientists to grow sufficient quantities of griffithsin in the modified plant to test the HIV entry inhibitors in clinical trials, said Dr. Kenneth E. Palmer, lead researcher of the study.

Anti-HIV microbicide gel directly targets entry of the virus and averts infection at the surfaces but at present, they are being produced using biologicals like bacteria E. Coli, an expensive process which is not cost-effective. In an effort that involved scientists from several research institutions in the United States and the United Kingdom, the genetic nature of the plant was altered using the tobacco mosaic virus, which produced griffithsin. The scientists infected more than 9,300 plants and managed to extract substantial amounts of the protein from the leaves of the transgenic plant.




Cellular Respiration and Carcinogenesis

Cellular Respiration and Carcinogenesis informs the reader about both basic and recent research in the field of cellular respiration and the effects of its dysfunction, alteration or attenuation on the development of cancer. It offers a fundamental understanding about how oxygen sensing and/or availability, programmed cell death, immune recognition and response, and glucose metabolism are closely linked with two major mechanisms or pathways of cellular respiration oxidative phosphorylation and glycolysis. The publication opens the dialogue that the etiology of cancer can be significantly attributed to the failure of one or multiple pathways of oxidative phosphorylation to normally burn fuel to generate energy. Keeping with its cutting-edge nature, the book provides a glimpse of cautionary evidence-based counterbalance to the recent and rapidly proliferating idea that utilization of fuel primarily via glycolysis is a hallmark of cancer development.

Contact: Springer Publishing Company, 11 West 42nd Street, 15th Floor, New York, NY 10036, United States of America. Tel: +1 (877) 687 7476.



This publication focuses on the mechanism of action of pharmacologic agents that regulate immune response and the physiologic, pathologic, and pharmacologic role of the products of immune response. Topics include cytokines and their receptors, monoclonal antibodies, immunosuppressive drugs, mechanisms and immunotherapy of allergic disease, acquired immune deficiency disease, regulatory T cells, and gene therapy. The book provides most basic principles of immunopharmacology by equally emphasizing the disciplines of immunology and pharmacology, which will be a very valuable tool for both the professional as well as graduate students.

Contact: Springer Publishing Company, 11 West 42nd Street, 15th Floor, New York, NY 10036, United States of America. Tel: +1 (877) 687 7476.



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