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VATIS Update Biotechnology . Mar-Apr 2007

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Biotechnology Mar-Apr 2007

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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Contents

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IN THE NEWS

China launches biosafety research centre

China has announced a National Agricultural Biosafety Science Centre to fend off invasive species and trace the potential impacts of genetically modified crops. The US$17.75 million centre is one of a dozen big science projects planned by the Chinese government. The National Development and Reform Commission, responsible for nearly all major investments by the central government, announced the plans in February.


The biosafety centre will comprise laboratories to investigate high-risk plant pathogens, insects and invasive plants, as well as quarantine facilities. It will be run by the Beijing-based Institute of Plant Protection of the Chinese Academy of Agricultural Sciences (CAAS) and is due to open in 2009. The centre is expected to provide a public platform for Chinese and foreign scientists to study biosafety issues related to agriculture, and also have a role in evaluating the impact of genetically modified crops on agriculture by recreating the environments in closed and controlled conditions. All data obtained in the centre will be shared with agricultural scientists nationwide, according to a CAAS newsletter.


www.scidev.net

Biocentre to strengthen Finnish life-science competence

The Universities of Helsinki, Kuopio, Oulu, Turku, Tampere and bo Akademi have on 7 February 2007 signed an agreement for the establishment of the Biocentre Finland co-operation network. The founding partners of Biocentre Finland are the A.I. Virtanen Institute of Molecular Sciences (University of Kuopio), Biocentre Oulu (University of Oulu), Biocentrum Helsinki (University of Helsinki), BioCity Turku (University of Turku and bo Akademi University) and the Institute of Medical Technology (University of Tampere). Other Finnish institutes, with international significance in life-science studies, may join Biocentre Finland.


The purpose of Biocentre Finland is to strengthen and internationalize Finnish research in the life sciences, biomedicine and biotechnology, and to promote a more efficient utilization of research results and implementation of new technologies in Finland. The Biocentre will collaborate actively with university hospitals and will create close contacts with clinical research, technical sciences, business and industry, and polytechnics. It will make proposals for universities concerning the development and funding of the research infrastructure in life sciences, biomedicine and biotechnology, and play an active role in developing researcher training in the field.


www.bionews.in

Stem cell research centre to come up in India

In India, the Centre for Liver Research and Diagnostics based in Hyderabad, in association with the Indian Council for Medical Research (ICMR), is setting up a stem cell research in Andhra Pradesh. The centre will be located at Rajender Nagar in Ranga Reddy district and will be headed by the noted gastroenterologist Dr. C.M. Habibullah. The centre will also have a research facility for regenerative medicine, hospital and animal house.


According to Dr. Habibullah, this would be an international centre, with all facilities to carry out industrial and academic research. Besides basic stem cell research, it would conduct research on Parkinsons disease, diabetes, neurology and other diseases. It will produce the stem cells required for treatment of various diseases and would also undertake contract research. The centre will establish a 100-bed hospital for stem cell therapy. Total cost of the project is estimated to be around Rs 1 billion.


Website: www.pharmabiz.com

Scotlands new programme in stem cell research

ITI Life Sciences of Dundee, Scotland, has initiated a new 9.5 million research programme to develop an automated process to produce high-quality human stem cells. This capability does not exist anywhere in the world, and its development will put Scotland at the forefront of stem cell research and bring closer stem cells-based therapeutics.


As part of this three-year programme, Swedish biotech company Cellartis AB is setting up an R&D and manufacturing facility in Dundee. The ITI programme will also involve the University of Glasgow, which brings world class expertise in molecular mechanisms that control cell signalling and development. The work will be carried out by the Universitys Faculty of Medicine and Faculty of Biomedical and Life Sciences. In bringing together this programme, ITI Life Science hopes to solve some of the main problems associated with producing high volumes of quality stem cells.


Website: www.bionity.com

Nigeria initiates Africas institute of science

Nigeria has allocated US$25 million to fund the first site of the African Institute of Science and Technology (AIST). Construction of the Gulf of Guinea Institute will begin in February in Nigeria, following the governments Petroleum Technology Development Fund approval of funding late last year, according to Mr. Desmond Akawor, Minister of State for the countrys Federal Capital Territory Administration.


The institute, to be located in a 240-hectare site in Abuja, is due to open in September. Its research focus will include biological sciences. It is one of the three primary sites for the AIST centres for excellence, announced in 2005 and reiterated at the African Union summit last month. It will also encompass smaller affiliated centres throughout sub-Saharan Africa. AIST, also called the Nelson Mandela Institute, is a public-private sector partnership aiming to produce more African scientists to help accelerate development in the continent.


Website: www.scidev.net

India emerging as key biotech leader in Asia

India is emerging as a key biotech leader in Asia, surpassing China for the first time in areas planted with biotech seed, according to Mr. Clive James, Chairman of the International Service for the Acquisition of Agri-biotech Applications (ISAAA). Citing the India example, Mr. James said the next decade of research in crops improved by biotechnology will include a major role for the rapidly increasing number of projects in Asia. ISAAA is a non-profit international network based at Cornell University in New York.


In 2006, India tripled from the previous year the area it planted in biotech cotton, its first commercialized biotech crop. India now has a total of 3.8 million biotech hectares against Chinas 3.5 million hectares. India is projected to invest US$80 million in 2007 to develop a national network of research laboratories.


With support from the United States Agency of International Development and Cornell University, India has been conducting research on major food crops it consumes drought and salt-tolerant rice, potato resistant to blight and eggplant resistant to shoot borers, Mr. James said. Plants with genes conferring some degree of drought tolerance, which are expected to become available in about 2010-11, will be very important for developing countries as drought is the most prevalent and main constraint to increased crop productivity worldwide, he said.


Website: www.bionews.in

South Africa accelerates development of biotech research

In South Africa, state research institutions and private-sector companies are forecast to spend about US$350 million on biotechnology and genetic engineering research and development over the next three years. Of this, US$70 million will be invested by the Department of Science and Technology (DST), US$161 million by other public sector sources, and US$119 million by private sector industry. Biotechnology and genetics loom very large in the national science and technology policy, according to Mr. Mosibudi Mangena, the Science and Technology Minister.


The National Biotechnology Advisory Council, inaugurated in November 2006, is a sub-committee of the National Advisory Council on Innovation. The country has so far established three Biotechnology Regional Innovation Centres, which form one of the implementing initiatives of the National Biotechnology Strategy that was adopted in 2001. A National Innovation Centre for Plant Biotechnology and a National Bioinformatics Network were created in 2004.


In 2006, the International Centre for Genetic Engineering and Biotechnology selected South Africa to host its third research laboratory, the other two laboratories being in Italy and India.


Website: www.checkbiotech.org

MARKET NEWS

Geneservice acquires DNA sequencing facility

Geneservice Ltd., the United Kingdom, has acquired the sequencing facility at the Biochemistry Department, University of Oxford. The aim is to create an Oxford-based one-stop-shop for genomics contract research, including: DNA sample processing, genotyping, mRNA expression analysis and microbiological clone management. In particular, the Oxford hub will provide customers throughout Oxford and neighbouring regions access to more than 10 years of DNA sequencing experience, besides other services.


The existing DNA sequencing facility within the Biochemistry Department will become Geneservices local service hub, with existing university personnel transferring to the company. Mr. Tom Weaver, Geneservices CEO, stated: We plan to grow the hub and its service offerings, particularly as the Department expands into new premises.


Website: www.geneservice.com 

Althea and Blueshift join hands for gene expression screening

In California, the United States, Althea Technologies and Blueshift Biotechnologies announced that Althea has received a SBIR award from the National Human Genome Research Institute to explore the potential for practical high throughput and low cost gene expression analysis.
The grant proposal is for the development of gene expression profiling methods that make use of Altheas proprietary strength in multiplexed PCR methods and Blueshifts IsoCyte platform, a high throughput laser scanner adapted from semiconductor inspection technology, which provides multi-colour fluorescence, anisotropy, as well as scatter images for high content and object-based multiplexed array formats. The combined technologies may enable implementation of quantitative gene expression profiling in an automated high throughput and low-cost platform, which provides highly specific and quantitative results for 768 samples per minute.


Website: www.bioresearchonline.com

Embrapa may form partnership with Monsanto

Empresa Brasileira de Pesquisa Agropecuria (Embrapa), the government-owned agricultural research company in Brazil, is negotiating with the American biotechnology company Monsanto to form a partnership to develop BT transgenic corn seeds resistant to caterpillars. Embrapa has been conducting research to obtain cultures of BT corn. If the Monsanto partnership is established, the corn gene used to produce the transgenic seeds will be from the American company.


The corn genetically modified to make it resistant to insects is an individual project of Empbrapa, which began developing it six years ago. But it decided to look for a partner to facilitate the project, which needs, millions of dollars according to Embrapa President Mr. Silvio Crestana. The state-owned company does not have enough the funds to launch such a project alone, especially to realize the biosecurity tests. So far, Embrapa has invested about US$2.38 million in its transgenic corn project.


Website: www.agbios.com

Chromos, Genitope sign cell line engineering deal

Canadas Chromos Molecular Systems Inc. and Genitope Corporation of California, the United States, have entered into a cell line engineering service agreement to develop a cell line using Chromos ACE System for potential use in the clinical and commercial manufacture of a biopharmaceutical product. Under the agreement, Chromos will engineer cell lines for the expression of a monoclonal antibody for Genitope using the ACE System.


Chromos ACE System is a versatile and potent biological engineering system based on proprietary artificial chromosome technology. It facilitates the rapid engineering of stable, high-expressing production cell lines for the manufacture of biopharmaceuticals. Recent data show that cell lines engineered by Chromos using the ACE System are capable of achieving monoclonal antibody yields of more than 4 g/l, a four-fold improvement, in a non-optimized bioreactor system.


Chromos has also used an ACE System-derived cell line to manufacture its lead product, CHR-1103. Over-
all, the speed, performance and versatility of the ACE System can provide time and cost savings in the production of biopharmaceuticals.


Website: www.pharmabiz.com

Trellis Bioscience and PDL BioPharma collaborate on new antibodies

In United States, Trellis Bioscience Inc., a private biotechnology company, is in collaboration with PDL BioPharma Inc. to use Trellis proprietary CellSpot technology to discover monoclonal antibodies directed against a proprietary PDL antigen.


Under the terms of the agreement, Trellis will use Antibody CellSpot to screen large populations of antibody-producing cells developed by the parties using a variety of immunization strategies. Trellis will select and deliver hybridomas to PDL BioPharma, which will conduct further research and development on the antibodies. PDL BioPharma will develop and commercialize any products discovered during the research collaboration, and Trellis will receive an upfront fee, milestone payments and royalties on the products discovered.


Website: www.bioresearchonline.com

BIO and IICA MoU to promote agricultural biotech

The Biotechnology Industry Organization (BIO) and the Inter-American Institute for Cooperation on Agriculture (IICA) have entered into a Memorandum of Understanding (MoU) to co-operate for the continued adoption of agricultural biotechnology in the Americas as part of IICAs Hemispheric Biosafety and Biotechnology Programme (HBBP). Under the MoU, both organizations will promote agricultural biotechnology initiatives that benefit the Americas around the Cartagena Protocol on Biosafety, the Convention on Biological Diversity, the Codex Alimentarius Commission, the International Plant Protection Convention, and World Trade Organization (WTO) agreements.


BIO President and CEO Mr. Jim Greenwood said that formalizing the collaborative efforts between BIO and IICA will promote the development of national and regional policies and regulatory frameworks for agricultural biotechnology, adding that more than 80 per cent of the current global biotech acreage was in the Americas. Dr. Jim Butler, Deputy Director General of IICA., said that the collaboration between BIO and IICA would make certain that more farmers and consumers receive the socio-economic, environmental and financial benefits associated with biotech crops.


BIO represents more than 1,100 biotechnology companies, academic institutions, state biotechnology centres and related organizations across the United States and 31 other nations. IICA is the specialized agency for agriculture of the inter-American system.


Website: www.monsanto.com

AstraZeneca acquires Arrow Therapeutics

The pharmaceutical major AstraZeneca has finalized the acquisition of Arrow Therapeutics Ltd., a privately owned biotechnology company in the United Kingdom, focused on the discovery and development of anti-viral therapies. The total share capital of Arrow Therapeutics will be purchased for US$150 million cash, subject to debt and working capital adjustment.


The deal is an important strategic step for AstraZeneca, strengthening its portfolio of promising anti-infective treatments. The anti-viral programmes developed by Arrow Therapeutics, include several different approaches towards Hepatitis C Virus (HCV) and Respiratory Syncytial Virus (RSV). The acquisition of Arrow Therapeutics augments AstraZenecas portfolio with pre-clinical and clinical compounds and programmes.


These assets include two anti-HCV compounds that target the novel NS5a protein, including A-831 in Phase I. Arrows most advanced compound is RSV604, a first-in-class, small molecule, oral anti-RSV compound.


Website: www.lifescienceworld.com

GENOMICS

A gene that lurks behind autoimmune diseases

A pinpointed region of chromosome 17, a gene named NALP1, could be a new target of treatment for autoimmune diseases, according to a new study. This is a particularly exciting discovery because NALP1, a gene known to control part of the immune system that serves to alert the body to viral and bacterial attacks, has not previously been specifically implicated in autoimmune diseases. The discovery resulted from a collaboration between St. George University of London, and the University of Colorado Denver Health Sciences Centre (UCDHSC) and Barbara Davis Centre for Childhood Diabetes, the United States.


The findings of this study, which followed 656 persons from 114 extended families in the United States and the United Kingdom who had multiple autoimmune diseases, give the researchers a clue as to why the immune system attacks one of the bodys own tissues. If the sensor NALP1 is over-reactive, it could trigger a response to the wrong stimulus, said lead investigator Professor Dorothy Bennett, St. Georges University. Since NALP1 appears to be part of our bodys early-warning system for viral or bacterial attack, this gives us ideas about how to try to discover the environmen-tal triggers of these diseases, said Dr. Richard Spritz, Director of the Human Medical Genetics Programme at UCDHSC.


Website: www.medicalnewstoday.com 

DNA sequence of Aspergillus niger genome published

Royal DSM N.V., the Netherlands, will soon publish the DNA sequence of the fungus Aspergillus niger, a common fungus that grows as a black mould on certain plants and is a common food contaminant. The work is the result of a research project carried out by DSM in which 29 international research groups participated.


DSM uses A. niger for the production of enzymes and compounds such as citric acid. These are mainly used in foodstuffs to improve taste, shelf life, texture, nutritional value, etc. At the beginning of this century, DSM began work on the complete DNA sequencing of A. niger and the identification of the functions of the different genes. The project has resulted in a high-quality genome sequence of 33.9 million base pairs with more than 14,000 unique genes. The (possible) functions of around 6,500 of these genes could be established.


Website: www.bionity.com

The gene that makes the man

Disorders of sexual development (DSD) or intersex conditions occur when the genetic sex does not match the genital sex for example, chromosomal males (XY) may be born with female genitals. In most DSD cases, the underlying genetic mutations have not been identified. Even 16 years after the Sex-determining Region Y chromosome (SRY) was identified as the master male gene in eutherian mammals, the genetic pathway through which SRY makes the male remains enigmatic.
Now a research team led by Dr. Vincent Harley at Prince Henrys Institute in Melbourne, Australia, has identified a gene, the deletion of which leads to an intersex condition male-to-female sex reversal in XY mice. The researchers identified a new gene Fibroblast Growth Factor Receptor 2 or FGFR2 that acts downstream of SRY and is essential for male development. FGF9 protein activates four FGF receptor subtypes 1, 2, 3 and 4 but FGFR1, 3 and 4 knockout mice exhibited no gonadal abnormalities. Hence, the researchers suspected FGFR2s role in sex determination.


The Harley laboratory has been studying the functions of SRY and a closely related gene, SOX9, having identified numerous mutations in both genes in XY females and made biochemical studies of the consequences of point mutations that result in failure to activate the testis pathway. Dr. Harley and team found that mice lacking one allele either of SOX9 or FGFR2 gene show no phenotypic abnormality, but when these strains are crossed with one another, the XY offspring show male-to-female sex reversal. This data supports a genetic interaction between FGFR2 and SOX9, Dr. Harley said, adding that the FGFR2 study will lead the way to screening of patients with intersex disorders for FGFR2 mutations.


Website: www.biotechnews.com.au

First draft of the human metabolome completed

Researchers at the University of Alberta, Canada, have announced the completion of the first draft of the human metabolome, the chemical equivalent of the human genome and the complete complement of all metabolites found in or produced by an organism. The scientists have catalogued and characterized 2,500 metabolites, 1,200 drugs and 3,500 food components that can be found in the human body.


The researchers say that the results of their work are the starting point for a new era in diagnosing and detecting diseases. A single base change in human DNA can lead to a 100,000X change in metabolite levels. The results of this research will have a significant impact on the diagnosis, prediction, prevention and monitoring of many genetic, infectious and environmental diseases, said Dr. David Bailey, President and CEO of Genome Alberta, one of the financiers of the project.


By measuring or acquiring chemical, biological and disease association data on all known human metabolites, the Human Metabolome Project Consortium, which consists of some 50 scientists based at the Universities of Alberta and Calgary, has spent the past two and half years compiling information on the 95 per cent of metabolites in the human metabolome that were unknown. With the data in the Human Metabolome Database, anyone can find out what metabolites are associated with which diseases, what the normal and abnormal concentrations are, where the metabolites are found, or what genes are associated with which metabolites.


Website: www.bio.com

First draft of horse genome published

The first draft of the horse genome sequence has been made freely available for use, according to the leaders of the international Horse Genome Sequencing Project. The National Human Genome Research Institute (NHGRI), the United States, funded the US$15 million effort to sequence the approximately 2.7 billion DNA base pairs in the horse (Equus caballus) genome. A team led by Dr. Kerstin Lindblad-Toh carried out the sequencing and assembly of the horse genome.


The researchers also produced a map of horse genetic variation, using DNA samples from a variety of modern and ancestral breeds, comprising 1 million single nucleotide polymorphisms (SNPs). This map will provide scientists with a genome-wide view of genetic variability in horses and help them identify the genetic contributions to physical and behavioural differences, as well as to disease susceptibility.


The initial sequencing assembly is based on 6.8-fold coverage of the horse genome, which means, on average, each base pair has been sequenced almost seven times over. The researchers plan to further improve the accuracy of the horse genome sequence and expect to deposit an even higher resolution assembly in public databases. Comparing the horse and human genomes will help medical researchers learn more about the human genome. It will also serve as a tool for veterinary scientists to better understand the diseases that affect equines.


Website: www.bioresearchonline.com

Genetic link to schizophrenia discovered

A joint United States-Japanese study suggests that gene mutations governing a key brain enzyme make people susceptible to schizophrenia. The research by scientists from the Massachusetts Institute of Technology and Riken Brain Science Institute might lead to new treatments for the psychiatric illness that afflicts an estimated 51 million people worldwide.


By studying genetically engineered mice and the genetic make-up of schizophrenic individuals, the scientists pinpointed the PPP3CC gene and other genes in the early growth response gene family (specifically, EGR3) as likely causes for the disease. Those genes are critical in the signalling pathway for the brain enzyme calcineurin, which is prevalent in the central nervous system and plays a role in many neuronal functions whose disturbances would result in the disorganized thinking, attention deficits, memory and language problems that characterize schizophrenia. The scientists confirmed that the PPP3CC gene is involved in diagnosed schizophrenia in Caucasian, African-American as well as Japanese individuals. EGR3 involvement was confirmed through a separate test.


Website: www.sciencedaily.com

MEDICAL BIOTECH

Gene therapy for AIDS

In Russia, scientists at the V.A. Engelgardt Institute of Molecular Biology, Russian Academy of Sciences, and the Vector Main Research Centre of Virology and Biotechnology created and tested on the cell culture three genetic structures that can suppress reproduction of human immunodeficiency virus (HIV-1) in human cells. These structures contain short nucleotide sequences that find the most conservative molecules among all RNA molecules, that is, sequences that do not change quickly and are important to the virus. These sequences are then damaged to halt virus reproduction.


The researchers embedded the gene structures created by them into cultivated lymphoid cells. Within 24-72 hours after introduction of genetic structures, the cells were infected by HIV (GKV-4046 culture). Several days later, the researchers assessed the degree of viral welfare by specific antigen accumulation. It was found that the genetic structures notably suppressed virus reproduction. The extent of damage to viral RNA depended on the viral dose received by the cell itself and on the sequence of the structure per se. The sequence aimed at the reverse transcriptase area of viral genome was the most efficient, being capable of suppressing the viral production in the cells by 91-98 per cent within three days. In the researchers opinion, similar genetic structures can be used in AIDS gene therapy.


Website: www.medicalnewstoday.com 

Second genetic defect for brittle bone disease identified

In the United States, researchers at the National Institutes of Health (NIH) and other institutions have found a second genetic defect that accounts for previously unexplained forms of osteogenesis imperfecta (OI), a disorder that weakens bones and causes frequent fractures. The affected gene contains the information for a protein named prolyl 3-hydroxylase 1 (P3H1). P3H1 is part of a complex of proteins that is crucial for refining collagen, an important building block for bone, to its final form. When the gene does not function, little or no P3H1 is produced, resulting in defective collagen and a form of OI. Besides NIH researchers, scientists from the University of Washington, Shriners Hospital for Children, Childrens National Medical Centre and Georgetown University Hospital were also involved in the study.


Unlike the majority, some cases of OI could not be explained by mutations in the collagen gene. In a previous study, NIH scientists had found a defect in the gene that codes for cartilage-associated protein (CRTAP), one of the proteins that work with P3H1 during collagen synthesis. The two defective genes explain cases of the disease that did not have a mutation in a collagen gene, as occurs with the dominant form of OI. As a result of the current and previous study, these formerly unexplained cases are now understood to be a recessive form of OI, in which two defective copies of a gene are needed to cause a particular trait.


Website: www.bioresearchonline.com

Protein that regulates efficacy of chemotherapy in breast cancer

Cancer researchers at Georgetown University Medical Centre, the United States, have taken a step towards understanding how and why a widely used chemotherapy drug works in patients with breast cancer. In laboratory studies, they isolated a protein, caveolin-1, showing that in breast cancer cells this protein can enhance cell death in response to the use of Taxol, one of two taxane chemotherapy drugs used to treat advanced breast and ovarian cancer. But in order to work, they found that the protein needs to be switched on, or phosphorylated.


This finding suggests the possibility of testing individual breast cancer patients for the status of such molecular markers as caveolin-1 in their tumours to determine the efficacy-to-toxicity ratio for Taxol. It offers insights into why some breast cancer cells become resistant to therapeutic drugs. Additionally, the study identifies caveolin-1 as a new molecular target for increasing the efficacy of taxanes, such as Taxol (also known as paclitaxel) and Taxotere (docetaxel), which stabilize a cells microtubules that send chemical signals to all parts of the cell, and which must be flexible if a cell is to divide.


In this study, the researchers show that in their breast cancer cell model that phosphorylated caveolin-1 increased cell death by activating other key regulators vital to both breast cancer progression and cell death, including: BCL2, the same protein that Taxol works on; p21, which controls cell cycle progression; and the tumour suppressor p53. If caveolin-1 is not phosphorylated, breast cancer cells appear to be resistant to Taxol treatment, the researchers concluded.


Website: www.medicalnewstoday.com

Sweet-toothed bacteria combat gut disorders

Professor Simon Carding at the University of Leeds, the United Kingdom, modified Bacteroides ovatus to release human growth factors, called cytokines, that repair the epithelial cells found in the lining of the gut, reducing the inflammation caused by inflammatory bowel disease (IBD). B. ovatus is widely distributed in the animal kingdom and is one of the good bacteria that helps to break down plant material to provide energy to the body. While bacteria and viruses have been used to deliver drugs in this way before, the major problem has been controlling the production of the drugs.


Prof. Carding has found a novel answer to this by linking the gene in the bacteria that breaks down xylan with the human gene that produces cytokines. Xylan is a sugar that is mainly found in tree bark, and naturally present in food in only low concentrations and not part of most peoples diets. The bacteria behave as normal until they encounter the xylan, which triggers them to produce the cytokines. A patient can control the dose they receive by controlling how much xlylan they eat; when the xylan runs out cytokine production stops.


Website: www.drugresearcher.com

Stem cell marker identified in head and neck cancer

Cancer stem cells are the small number of cancer cells that replicate to drive tumour growth. Researchers believe current cancer treatments sometimes fail because they are not attacking the cancer stem cells. By identifying the stem cells, researchers can then develop drugs to target and kill these cells.


Researchers at the University of Michigan Comprehensive Cancer Centre and Stanford University School of Medicine took tumour samples from patients undergoing surgery for head and neck squamous cell carcinoma, including cancers of the tongue, larynx, throat and sinus. Cells from the samples were separated based on whether they expressed a marker on their surface called CD44. The sorted cells were then implanted into immune-deficient mice to grow tumours.


The cells that expressed CD44 were able to grow new tumours, while the cells that did not express CD44 did not grow new tumours. The tumours that grew were found to be identical to the original tumours and to contain cells that expressed CD44 as well as cells that did not express the marker. This ability to both self-renew and produce different types of cells is a hallmark of stem cells, which have been identified in several other cancer types.


Website: www.bio.com

How T-cell leukaemia viruses evade bodys defence system

Scientists at the National Cancer Institute (NCI), the United States, have discovered how human T-cell leukaemia virus type 1 (HTLV-1), which infects about 20 million people worldwide, evades being held in check by one of the bodys natural defence mechanisms. The study details how an enzyme, called hA3G, is prevented from being packaged into virus particles and thus cannot perform its normal function of inhibition of viral replication. When a virus infects a cell, it replicates its genetic material and packages it into new virus particles. Preventing the packaging of hA3G may contribute to the persistence, dissemination and the potentially lethal nature of the virus.


A number of human and nonhuman viruses that cause cancer or AIDS are susceptible to hA3G-mediated destruction. However, some viruses have adopted ways to avoid this intrinsic cellular defence mechanism. Each virus has developed a different method for thwarting hA3Gs antiviral effects. In HTLV-1, if hA3G becomes incorporated into viral particles, this can start a process that will degrade and deactivate the virus itself. The researchers, led by Dr. David Derse in the HIV Drug Resistance Programme at NCIs Centre for Cancer Research, found that mutating certain amino acids in the virus capsid, or core protein, caused increased levels of hA3G to be incorporated into virus particles. This strengthened the ability of hA3G to inactivate the virus. Virus particles that were not mutated still resisted hA3G.


This finding should aid researchers in their basic understanding of the mechanisms of circumventing viral longevity, and possibly assist in preventing some types of cancer, said NCI Director Dr. John E. Niederhuber.


Website: www.nih.gov

Antibody therapy for psoriasis

The results of a Phase II clinical trial showed that patients with moderate to severe plaque psoriasis experienced significant clearance of the skin disease, after receiving subcutaneous injections of CNTO 1275 antibody, developed by Centocor, a biotech company based in Philadelphia, the United States. Psoriasis is a chronic, immune-mediated disease, resulting from inflammation in the skin and overproduction of skin cells that accumulate on the surface causing scaly plaques that itch and bleed.


CNTO 1275, Centocor fully human monoclonal antibody developed for the treatment of moderate to severe plaque psoriasis, targets the naturally occurring proteins interleukin-12 (IL-12) and interleukin-23 (IL-23). CNTO 1275 has been shown to effectively block the interaction of IL-12 and IL-23 with the surface of immune cells. According to Dr. Gerald Kreuger, lead author of the study from University of Utah, At week 12 in this investigational study, the majority of patients treated with CNTO 1275, regardless of dosing, experienced significant skin clearance and sustained improvements in physical, emotional and social well being.


Website: www.drugresearcher.com

PROTEOMICS

Light-sensitive protein found in many marine bacteria

Researchers at the United States Department of Energys Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley have demonstrated that when the ability to respire oxygen is impaired, bacterium equipped with proteorhodopsin, the light-sensitive protein, will switch to solar power to carry out vital life processes.
Dr. Jan Liphardt, a biophysicist at Berkeley Lab explained: By harvesting light, proteorhodopsin enables bacterial cells to supplement respiration as a cellular energy source. This ability to withstand oxygen deprivation probably explains why so many ocean bacteria express proteorhodopsin. He added that microbes that can simultaneously harvest energy from several different sources may be better at producing biofuels than microbes that can only utilize a single energy source. Our thinking was that if you had a system that could harvest energy from two different sources and you knocked out one of those sources, then you would probably maximize the alternative energy source, Dr. Liphardt said.


To observe proteorhodopsin in action and measure its effects, Dr. Liphardt and his colleagues genetically engineered a strain of Escherichia coli that would express the light-sensitive protein. The researchers monitored E. coli cells and observed the response to light of the proton motive force (pmf), the electrochemical potential of protons across cellular membranes that bacteria use as the energy source.
They found that if light was shined on E. coli cells when their respiration was impaired, the cells would swim when they were exposed to green light, but stop when they were exposed to red light. In the absence of the azide respiratory poison, green light had no effect on the flagellar motors of these proteorhodopsin-equipped E. coli. By measuring the pmf of individual illuminated cells under different concentrations of azide or various degrees of lighting, the Berkeley researchers were able to quantify the coupling between light-driven and respiratory proton currents. At the highest azide concentrations, the average cell velocity was increased 70 per cent upon green light illumination. In the control study, normal E. coli cells, which do not express proteorhodopsin, had no response to the green light.


Website: www.sciencedaily.com

Motor protein plays a key role in neuron connection

In another piece of the puzzle of how neurons form connections, Dr. Wen-Cheng Xiong and her colleagues at the Medical College of Georgia, the United States, have found that myosin X travels a portion of a neurons backbone called the actin filament, a sort of two-way highway in the cells highest traffic area. Part of its cargo is DCC receptor, which needs to move from the central nucleus where it is synthesized to the cells periphery. At the periphery, DCC interacts with netrin-1, a guidance cue that helps axon grow in the right direction. Cells eventually communicate through synapses at the end of these cellular projections.


Growth is precisely controlled during development; errant growth can impair brain connectivity. Dr. Xiong says, Myosin X gets the DCC receptor where it needs to be so that it can interact with netrin-1. The rapidly moving protein degrades easily and needs tight regulation. Dr. Xiong suspects that the function of myosin X changes as the neuron develops. She has documented that in the late stages of development, when the axon needs to stop growing, a shorter molecule without motor is expressed. She suspects that negative function surfaces when the spinal cord is cut and plans to examine whether the protein is degraded in spinal cord injuries.


Website: www.eurekalert.org

Protein that awakens sleeping genes

For several years now, cancer researchers have been studying a mechanism that contributes to the development of malignant tumours: the cell attaches small molecules containing a carbon atom, called methyl groups, to specific building blocks of DNA, thereby individually switching off the genes thus labelled. This silencing also affects the function of many tumour suppressor genes, which, in their unmethylated state, put the brakes on uncontrolled cell growth. In contrast to real mutations, where DNA building blocks are exchanged or lost, these epigenetic changes are reversible and therefore considered a promising approach in fighting cancer. Now, scientists at the German Cancer Research Centre (Deutsches Krebsforschungszentrum, DKFZ) have discovered a protein that activates epigenetically silenced genes.


Scientists have already found out how the methyl groups are attached. The reverse process of demethylation, however, is poorly understood. DKFZ researchers, led by Dr. Christof Niehrs and Dr. Frank Lyko, have identified the protein Gadd45a as a key player in demethylation. Gadd45a is a long known protein that is involved in many cellular processes. The researchers showed that an increase of Gadd45a levels in the cells wakes up deactivated genes from their sleep. Control experiments showed that methyl groups are no longer attached to genes thus reactivated. In contrast, if Gadd45a is switched off, hypermethylation of many DNA areas results. When removing the methyl groups, Gadd45a interacts with enzymes that are involved in DNA repair. The study indicates that Gadd45a induces DNA-cutting enzymes of the DNA repair troops to remove the methylated areas, which are then replaced again by unmethylated building blocks.


Website: www.bionews.in

Crucial protein role in deadly prion spread

A single protein plays a major role in deadly prion diseases by smashing up clusters of these infectious proteins, creating the seeds that allow fatal brain illnesses to quickly spread, a study by research at the Brown University, the United States, shows. The findings are exciting because they might reveal a drug intervention to control the spread of prions, which cause mad cow disease and scrapie in animals and Creutzfeldt-Jacob, Alzheimers and Parkinsons diseases in humans.


Dr. Tricia Serio, the lead researcher of the project says, The protein fragmentation we studied has a big impact on how fast prion diseases spread and may also play a role in the accumulation of toxic proteins in neurodegenerative diseases like Parkinsons. Dr. Serio and her team had earlier shown that prions self-replicating proteins that cause fatal brain diseases convert healthy protein into abnormal protein through a rapid process.


This good-gone-bad conversion is one way that prions multiply and spread disease. But scientists believe that there is another crucial step in this propagation process fragmentation of existing prion complexes. Once converted, clusters of infectious protein are smashed into smaller bits, a process that creates seeds so that prions multiply more quickly in the body. Dr. Serio and team found by studying Sup35 a yeast protein similar to the human prion protein PrP that Hsp 104, a molecule known to be required for prion replication, functions as this protein crusher. So, a drug that blocked the activity of Hsp104 could seriously slow down the progression of prion-related diseases, the scientists have concluded.


Website: www.bio.com

New protein super-family

Biologists have discovered a new super-family of developmental proteins that are critical for cell growth and differentiation and whose further study is expected to benefit research on cancer and the nerve-cell repair. The protein super-family, which existed before the emergence of animals about 850 million years ago, is of major importance for understanding lifes evolution. The discovery was led by Prof. Randen Patterson and Dr. Damian van Rossum at Penn State University, Pennsylvania, and collaborators at Johns Hopkins University, Maryland, the United States.


This super-family is highly divergentalso evolves rapidly, so its proteins may provide a model system for investigating how rapidly mutating genes contribute to, and are likely necessary for, the diversity and adaptability of animal life, explains Prof. Patterson. The new protein super-family is named DANGER, an acronym for Differentiation and Neuronal Growth Evolve Rapidly. The relationship of the six family members comprising the DANGER super-family escaped detection due to the high rates of mutations between family members, although a few family members had been detected previously and had been shown to control the differentiation of cells into organs in worms, fish and mice. Deletion of their DANGER genes led to structural changes and prenatal death.


These findings also have clinical relevance, say the researchers. Many DANGER proteins are surrounded by transposable elements, which are pieces of DNA around genes that help the genes migrate back and forth throughout the genome, Prof. Patterson says. This feature helps DANGER genes move throughout the genome, which could have positive or negative health consequences. One member of the gene family resides in the genome at an area responsible for a human disease, the Smith-Magenis syndrome, while another member has been identified as playing a role in the development of the nervous system.


Website: www.sciencedaily.com

New function of protein kinase pathway in tumour suppression

A team of scientists led by Prof. Peiqing Sun and Prof. Jiahuai Han at The Scripps Research Institute have discovered a surprising new function of a well-known signalling pathway that, when activated, can inhibit tumour development. This finding may lead to the development of drugs that can serve as an effective cancer therapy by artificially activating this pathway in cancer cells.


The research, which was conducted on both human cell culture and rodent models with skin cancer or lymphoma, identified one vital element of an anti-tumour defence response called senescence (cellular aging) p38-regulated/activated protein kinase (PRAK). The researchers found that PRAK is needed for ras to induce senescence in vitro in normal cells derived from a mouse. They introduced double-strand RNA into normal human fibroblast cells to inhibit the expression of PRAK and then activated the ras oncogene in these cells. The results were identical to those in mouse cells. When PRAK was inactivated in normal human cells, these cells did not undergo premature senescence.


A group of PRAK knockout mice and a group of normal mice were treated with DMBA, an environmental pollutant found, which can induce ras mutations and cause skin tumour. It was found that the mice lacking the PRAK gene were more susceptible than wild-type mice to skin tumour induction by DMBA. This indicated that the presence of the normal PRAK gene suppresses tumour formation in vivo too.


Website: www.bionity.com

Turning a cellular sentinel into a cancer killer

Research by the Howard Hughes Medical Institute (HHMI), the United States, has yielded two strategies to reactivate the p53 gene in mice, causing tumours to self-destruct. The p53 protein is called the guardian of the genome because it triggers the suicide of cells with damaged DNA. Inactivation of p53 can set the stage for the development of different types of cancer. The research showed for the first time that inactivating the p53 gene is necessary for maintaining tumours. The studies were carried out independently by two HHMI research teams, one led by Dr. Tyler Jacks,


Massachusetts Institute of Technology and the other by Dr. Scott Lowe at Cold Spring Harbour Laboratory.
To reactivate p53, Dr. Lowe and his colleagues used a genetic technique they had developed to induce an aggressive form of liver cancer in mice. Although they had inactivated p53 in the mice, they genetically engineered the mice so that they could reverse p53 inactivation by giving doxycycline to the animals. Dr. Lowes team suppressed p53 protein levels using RNA interference (RNAi), which had been modified so that RNAi could be switched off by the antibiotic. When the team reactivated p53 in the mice, it found that the liver tumours had fully disappeared. We expected the tumour cells to undergo programmed cell death, or apoptosis. But instead, we saw evidence for a very different process that p53 also regulates senescence, or growth arrest, said Dr. Lowe. Indication was of an unknown mechanism by which cancers can trigger the immune system.


Dr. Jacks and colleagues used a different technique to reactivate p53 in lymphomas and sarcomas. They produced mice whose cells did not have p53 activity, and these mice were genetically engineered so that the drug tamoxifen could be used to switch on p53 activity. The researchers saw two distinct tumour phenotypes. In lymphomas the responses were rapid, extensive and were accompanied by the induction of apoptosis. In the sarcomas, the response was less rapid often less extensive and was not accompanied by apoptosis. Instead the cells underwent cell cycle arrest with features of senescence, said Dr. Jacks. There was no evidence that restoring p53 affected normal cells.


Website: www.bio.com

AGRI BIOTECH

New mechanism for nutrient uptake discovered

Biologists at the Carnegie Institutions Department of Plant Biology have discovered a new way that plant cells govern nutrient regulation neighbouring pore-like structures at the cells surface physically interact to control the uptake of nitrogen. It is the first time scientists have found that the interaction of neighbouring molecules is essential to this regulation. Since plants, animals, fungi and bacteria all share similar genes for this activity, the scientists believe that the same feature could occur across species. The discovery has widespread potential, from understanding human diseases, such as kidney function, to engineering better crops.


Every cell in every organism has a system for bringing in nutrition and expelling waste, explained lead author Dr. Dominique Loqu. Some are through pore-like protein structures called transporters, which reside at the surface of the cells outer membrane. Each pore is capable of transporting nutrients individually, so we were really surprised to find that the pores simply cant act without stimulation from their neighbours.
Plants import nitrogen in the form of ammonium from the soil. The researchers found that the end portion, the C-terminus, of the protein Arabidopsis ammonium transporter (AtAMT1;1), located at the surface of the cell membrane, acts as a switch. The terminus physically grabs a neighbouring short-chain molecule, binds with it, and changes the shape of itself and its neighbour, thereby activating all the pores in the complex.


The rapid chain-reaction among the different pores allows the system to shut down extremely fast and can even memorize previous exposures, noted co-author Dr. Wolf Frommer. The scientists dont yet know what triggers the rapid shut-off. They think it might be phosphorylation, where a phosphate molecule is introduced to another molecule, changing the latter, and preparing it for a chemical reaction. They have found a site for phosphorylation and are looking at this possibility further.


Website: www.eurekalert.org

Tobacco genetically engineered to produce vaccine

Scientists have genetically engineered tobacco plants to produce a protein for a vaccine against amoebiasis a disease predominantly affecting Latin America, Africa and Asia. According to the researchers, Dr. Henry Daniell and colleagues at the University of Central Florida in the United States, the method used achieves high production levels at a low cost and also prevents modified genes from crossing to other plants in the environment.


The researchers added the gene for a molecule that prompts an immune response in humans the antigen to the chloroplasts of the tobacco plant. With this method, the gene is not carried in the plants pollen and so cannot migrate to other plants. The tobacco-derived antigen successfully prompted an immune response in animal tests that was 4-20 times higher than that from other engineered antigens. The researchers calculate that an average yield of 24 mg of vaccine antigen per plant could produce 29 million doses of vaccine per acre of the transgenic crop. They say future development should be directed towards using carrot or lettuce plants, paving the way for a cheap oral vaccine.


Website: www.scidev.net

Watercress: anti-cancer superfood

Scientists at the University of Ulster, Ireland, have revealed that eating watercress daily can significantly reduce DNA damage to blood cells, which is considered to be an important trigger in the development of cancer. The research found that in addition to reducing DNA damage, a daily portion of watercress also increased the ability of those cells to resist further DNA damage caused by free radicals.


Prof. Ian Rowland, who led the research project, said: What makes this study unique is it involves people eating watercress in easily achievable amounts, to see what impact that might have on known bio-markers of cancer risk, such as DNA damage. The dietary trial involved 30 healthy men and 30 healthy women (including 30 smokers) eating an 85 g of fresh watercress every day for eight weeks. The single blind, randomized, crossover study was carried out with volunteers aged between 19 and 55. The volunteers ate one daily portion of watercress in addition to their normal diet. The beneficial changes were greatest among the smokers. This may reflect the greater toxic burden or oxidative stress among the smokers.
The key findings of the watercress diet are:
 
  • Significant reduction in DNA damage to lymphocytes by 22.9 per cent.
     
  • Reduction in DNA damage to lymphocytes by 9.4% when a sample was challenged with the free radical generating chemical hydrogen peroxide.
     
  • Reduction in blood triglyceride levels by an average of 10%.
     
  • Significant increase in blood levels of lutein and beta-carotene, which have antioxidant activity, by 100% and 33% respectively.
     

Website: www.bionews.in


Unique tomatoes top in anti-oxidants

Deep red tomatoes get their rich colour from lycopene, a disease-fighting anti-oxidant. A new study, however, suggests that a special variety of orange-coloured tomatoes provide a different form of lycopene, one that our bodies may more readily use. Researchers found that consumption of a sauce from these orange tomatoes, called tangerine tomatoes, caused a noticeable boost in this form of lycopene in consumers blood.


While red tomatoes contain far more lycopene than orange tomatoes, most of it is in a form that the body doesnt absorb well, said Dr. Steven Schwartz, the studys lead author and a professor of food science and technology at Ohio State University, the United States. The participants in the study who ate orange tomato sauce, on the other hand, consumed less lycopene but absorbed far more of it than they would have if it had come from red tomatoes. The tomatoes used for this work were developed specifically for the study.


Lycopene is a carotenoid that contains a variety of related compounds called isomers. Isomers share the same chemical formula, yet differ in chemical structure. In the case of tomatoes, the different lycopene isomers play a part in determining the fruits colour. There is an abundance of several of these isomers, called cis-lycopenes, in human blood. The researchers do not know if tomatoes rich in cis-lycopene will provide greater health benefits to humans, but the studys results suggest that tomatoes can be used to increase both the intake and absorption of compounds that are beneficial to health.


Lycopene absorption from the tangerine tomatoes was 2.5 times higher than that absorbed from the beta carotene-rich tomatoes and from typical red tomato varieties. Cis-lycopene levels spiked about five hours after eating the tangerine tomato sauce and at this point during absorption, the levels were some 200 times more than those of trans-lycopene, which were nearly non-existent. While cis-lycopene is by far the most abundant isomer in these tomatoes, they do contain trace amounts of trans-lycopene. The participants bodies also readily absorbed beta-carotene from the beta carotene-rich tomatoes.


Website: www.esearchnews.osu.edu

Key to salt-tolerant wheat uncovered

At the Commonwealth Scientific and Industrial Research Organization (CSIRO), Australia, recent research by plant scientists has described how two genes known as Nax1 and Nax2 work by excluding salt from different parts of the plant: one from the roots, the other from the leaves. The discovery of the two genes, which are the subject of international patents, could be significant for their implication on salt-tolerant crops. Over six per cent of the worlds arable land is affected by salinity, and salt-tolerant crops could help in the remediation of these, besides helping to stabilize the soil from wind and water erosion.


The two genes originally came from Triticum monococcum, a wheat ancestor, said research team leader Dr. Rana Munns. They were unwittingly crossed into a durum wheat line about 35 years ago and are normally not present in any modern wheat. The project began when the CSIRO team used a highly accurate selection method based on their understanding of how plants tolerate salt to identify wheat varieties that could cope with higher salinity. The team used their knowledge of the two genes to construct molecular markers, which are now in use in CSIROs wheat breeding programme. A durum wheat variety as salt-tolerant as bread wheat is in advanced field trials, and could be commercially available in three years. Dr. Munns said that the aim is to eventually produce wheats able, like barley, to grow in very saline soils.


Website: www.foodnavigator.com

Beta-carotene suitable to colour low-fat mayonnaise

Beta-carotene, a carotenoid extensively used as a colorant, improved the colour of reduced-fat (RF) mayonnaise using beta-glucan without affecting texture, says new research by Dr. Rujirat Santipanichwong and Dr. Manop Suphantharika from Mahidol University in Bangkok, Thailand. While the researchers note that this is not the first time that beta-carotene has been used to colour low-fat mayonnaise and salad dressing, it is the first incorporation of both beta-glucan and carotenoids in the mayonnaise.


The researchers reported the results of testing beta-carotene or lutein in concentrations ranging from 25 mg/kg to 75 mg/kg in RF mayonnaise, prepared by replacing 50 per cent of the oil content with beta-glucan. They said that the colour characteristics of the RF mayonnaise samples improved mainly by an increase in yellowness, as a function of increasing colorant concentrations. They also reported that lutein appeared to destabilize the mayonnaise emulsion.


On the contrary, the stability of the emulsions was almost unaffected by beta-carotene addition, they reported. The reason is that the lutein initially localized at the oil droplets surface was spontaneously transferred to the aqueous phase and destabilized the emulsions. On the other hand, beta-carotene was initially localized in the droplets centre and needed longer time to be transferred oil droplet surface and then to the aqueous phase.


Website: www.foodnavigator.com

PUBLICATIONS

Gene Sharing and Evolution

The term gene sharing was coined by Mr. Joram Piatigorsky and colleagues to describe the use of multifunctional proteins as crystallins in the eye lens. In Gene Sharing and Evolution Mr. Piatigorsky explores the generality and implications of gene sharing throughout evolution and argues that most, if not all, proteins perform a variety of functions in the same and in different species, and that this is a fundamental necessity for evolution. The extensiveness of gene sharing and protein multi-functionality offers a way of responding to these questions that sheds light on the complex inter-relationships among genes, proteins and evolution.

Genes in Conflict

In evolution, most genes survive and spread within populations because they increase the ability of their hosts (or their close relatives) to survive and reproduce. But some genes spread, in spite of being harmful to the host organism, by distorting their own transmission to the next generation or by changing how the host behaves towards relatives. Thus, different genes in a single organism can have diametrically opposed interests and adaptations.


Genes in Conflict is the first book to tell the story, covering all species from yeast to humans, of selfish genetic elements, those continually appearing stretches of DNA that act narrowly to advance their own replication at the expense of the larger organism. The book introduces the subject of selfish genetic elements in all its aspects, from molecular and genetic to behavioural and evolutionary. The authors give us access for the first time to a crucial area of research with its own logic and interconnected questions.

For the above publications, contact: Harvard University Press, Fitzroy House, 11 Chenies Street, London WC1E 7EY, United Kingdom. Tel: +44 (20) 7306 0603; Fax: +44 (20) 7306 0604


E-mail: info@HUP-MITpress.co.uk


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