VATIS Update Biotechnology . Mar-Apr 2005

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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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United Nations bans reproductive cloning

The legal committee of the United Nations General Assembly voted by a slim majority in favour of a non-legally binding agreement that asks member states to prohibit reproductive cloning and adopt legislation to respect human dignity and life. If adopted and approved by the General Assembly, the declaration is not legally binding, so there would be no penalties for countries that do not implement relevant legislation.

This latest declaration, slightly modified from an earlier proposal put forth by Italy in November 2004, was drafted as a compromise between two deeply divided groups. The United Nations had been trying to reach agreement on a stance on cloning for more than two years, during which time the member states were split between two resolutions. The first, put forth by Costa Rica and supported by the United States, proposed a total ban on all forms of cloning. The other, submitted by Belgium and supported by the United Kingdom, recommends a ban on human reproductive cloning and left the decision about therapeutic cloning to individual states.


Biotech park to host animal resource facility

A National Animal Research Facility (NARF) is slated to come up on the premises of Shapoorji Pallonji Biotech Park, based in Hyderabad, India. This facility will help research in biotechnology and pharmaceuticals. For this project, the Department of Biotechnology will provide US$45 million, while the Andhra Pradesh government has allotted 100 acres of land. NARF would be bigger than the primate research centre coming up at Mumbai, which proposes to have 7,500 breeding stocks. According to Dr. M.K. Bhan, Secretary, Department of Biotechnology, entrepreneurs and researchers have to follow basic policy tenets for sustainable innovation respect for intellectual property rights and a scientific regulatory framework for research relations between the academia and industry.

Express Pharma Pulse, 17 March 2005

India launches draft strategy for biotech development

The Department of Biotechnology, India, unveiled a draft strategy for developing biotechnology over the next decade. The strategy places special emphasis on easing regulatory mechanisms and increasing biology education and training, which would help the biotechnology sector to generate revenues of up to US$5 billion annually and create about a million jobs by 2010. The draft strategy proposes setting up an autonomous National Biotechnology Regulatory Authority to approve biotechnological products, which include agricultural products and transgenic crops, pharmaceuticals and industrial products, and transgenic food, feed and animal aquaculture.

Apart from focusing on regulatory mechanisms and human resources, the government will set up a national task force on education and training to formulate model undergraduate and postgraduate courses in life sciences, create special scholarships, raise the number of PhD fellowships from 50 to 200, and increase the exposure of students to industry and national institutes. New centres of excellence will also be set up in molecular medicine, herbal medicine, food biotechnology, biomaterials and devices, as well as bioinformatics.


UAE plans US$400 million biotechnology park

The United Arab Emirates (UAE) plans to create a US$400 million research and development park in Dubai, to be called DuBiotech. This project was launched on 1 February 2005 with two main initiatives an industrial cluster and a Foundation for Research and Innovation. The biotech park will collaborate on research with universities, medical research institutions and even non-governmental organizations in the United Arab Emirates and the wider Gulf region, as well as promote the use of biotechnology to bring social, economic and environmental benefits. Construction of the park is expected to begin in the second half of 2005 over a 3 km2 area and companies can commence operations by the second quarter of 2006.

By allowing 100 per cent foreign ownership and repatriation of profits, as well as zero tax, the industrial cluster is intended to attract companies active in biotechnology and pharmaceutical R&D. The park would also house other firms offering support services such as venture capital, legal services and training tailored to the biotechnology sector. On the other hand, the Foundation for Research and Innovation will channel government funding into R&D efforts in fields such as medical genetics, stem cell research, crop biotechnology and pharmaceutical research. It will even act as a business incubator, providing financial assistance and support to help commercialize promising innovations.


Irans first GM rice grown

Researchers at the Agricultural Biotechnology Research Institute of Iran have developed the countrys first genetically modified (GM) rice, which has been approved by national authorities and is being grown commercially. This rice variety has been modified to resist attacks from insects by inserting a bacterial gene, which produces a toxin that kills insects but is harmless to birds and mammals. The study was conducted along with the Philippines-based International Rice Research Institute using a local variety of aromatic rice, Tarom molaii.

Following laboratory tests, the GM rice was grown in a greenhouse and a total of six generations grown in field experiments from 1999 to October 2004. In trials, the new GM strain killed close to 100 per cent of the four species of insect pests attempting to feed on it. Furthermore, it showed no abnormal patterns of growth in field trials and differed from non-GM rice only in its ability to resist pests. Additional tests showed the modified rice to have the same nutritional value as the variety it was developed from and did not cause any adverse health effects when consumed.


Brazil opens door to GM crops

Brazil opened its market this year to genetically modified (GM) crops, after 10 years of prohibition. Dr. Jorge Guimaraes, President of Brazils biotechnology regulator the CTNBio, expressed that there was considerable demand both industrially and scientifically for biotechnology in Brazil. In anticipation of the new law, biotech seed firms have been ramping up their multiplication of GM soybean seeds for the October planting season.


Scientists develop vitamin-enriched GM rice

Scientists at Syngenta, the United Kingdom, have developed a new genetically modified (GM) strain of Golden Rice, which produces 20 times more -carotene than previous varieties. The human body converts -carotene into vitamin A and the new breakthrough could reduce deficiency of the vitamin and childhood blindness in developing nations. Syngenta will make the GM rice available for free to research centres across Asia to begin field trials if approved by their respective governments.


Free access GM toolkit

Dr. Richard A. Jefferson, founder of the Biological Innovation for Open Society, Australia, and co-researchers have developed a new method of genetically modifying plants and is making this discovery accessible to other researchers through open source licensing. The technique would be available for free to scientists from developing countries, who may otherwise be unable to afford research on genetic modification because of the prohibitive costs of getting a licence to use the existing technique. The present method, which relies on Agrobacterium to transfer genes to plants, is protected by a complicated and fragmented system of patent ownership.

Researchers from CAMBIA, a research centre affiliated to Charles Sturt University, found that other species of bacteria can also transfer foreign genes into plants. Although this method will still be patented, open source licences prevent an individual or group from holding a monopoly over information they have discovered or created. The only restrictions applied are that users share any improvements, safety information and regulatory data, and preserve the opportunity for others to use and improve the technology. Dr. Jefferson opined that free access would help scientists collaborate under a rule-set that assures as far as possible that the original work will be retained as building blocks, transparently evaluated and incorporated into new products.



Pfizer to acquire Indun Pharmaceuticals

In the United States, Pfizer Inc. will acquire San Diego-based Indun Pharmaceuticals Inc., a biopharmaceutical company focused on the discovery and development of therapies to control apoptosis. Indun has over 150 patents covering drug targets, new chemical entities, drug screening assays, diagnostics and antibodies. The firms technology centres on controlling caspase activity. Caspases are a group of cellular proteases involved in the pathway of apoptosis and inflammation. Indun has developed therapeutic applications focused on inhibiting caspase activity as potential treatments for liver disease and inflammation. Other projects targeting the activation of caspases as potential treatment for cancer are ongoing.

Indun has built a leading technology platform in controlling caspase activity based on IDN-6556 caspase inhibitor, and in it Pfizer saw potential application in treating liver damage associated with viral and non-viral disease plus other areas of significant unmet medical need. The acquisition is expected to close during the second quarter of 2005.

Express Pharma Pulse, 3 March 2005

Proteomics market to reach US$17.5 billion by 2009

Business Communication Co. (BCC), the United States, predicts that sales in the worldwide DNA sequencing and proteomics markets are expected to rise at an average annual growth rate of 17.6 per cent from US$7.8 billion in 2004 to US$17.5 billion in 2009. The compulsion to discover and develop new therapeutics at a lesser cost and within shorter time-frames has led to numerous pharmaceutical and biotechnology firms actively seeking out alternative yet equally effective ways that justify the mammoth costs involved with bringing a drug on to the market. According to the forecast, sales include products like microarrays and biochips as well as test kits to detect airborne chemical warfare agents and protein structure modelling tools. Beyond 2009, growth will depend on new applications and global market penetration.

The DNA microarray market is one area of the total research products market that recorded a robust growth worldwide due to a strongly installed base. With several different companies on the market which include Affymetrix, NimbleGen and Agilent growth is expected to touch US$937 million in 2010 from the US$596 million in 2003, according to figures from Frost and Sullivan. Drug discovery and healthcare are currently two of the largest market sectors, representing some 46 per cent and 20 per cent, respectively, of revenues in 2004. BCC added that growth in the healthcare sector was expected to arise from a compelling need to lower the overall cost of healthcare by means of early diagnosis of diseases. Proteomics sector has been growing more by a diffusion process as new technologies gradually replace older lab methods.


Foreign companies set up offices in Lucknow Biotech Park

The American Biotech Research Association has decided to set up an office in India, at the Lucknow Biotech Park (LBP), to develop naturaceuticals (nutraceuticals). According to Dr. P.K. Seth, CEO of LBP, facilities available for drug discovery at the Central Drug Research Institute (CDRI), the pilot plant facility for herbal formulations at the National Botanical Research Institute (NBRI) and bioevaluation facility for plant products at the Central Institute of Medicinal and Aromatic Plants (CIMAP) were helping attract foreign firms.

LBP offers start-up, incubation and development of innovation-led high growth, knowledge-based bio-business and state-of-the-art infrastructure facilities for the biotech sector. Technology know-how and laboratory facilities in the area of modern biotechnology at other centres of knowledge creation such as CSIR and ICAR laboratories, IIT Kanpur, Universities and medical institutions are also to be made available to the entrepreneurs. These include NABL-accredited toxicology testing facility following GLP and a GLP-conforming animal house at the Industrial Toxicology Research Centre.

LBP would soon enjoy all the tax benefits that are available to biotech parks in the country. It houses polynet and poly houses for hardening of tissue culture-raised plants and temperature and humidity controlled glass houses for maintaining high-value aromatic and medicinal plants. A network facility of LBP for rural development is also being set up on a 28 acres plot.

Chronicle Pharmabiz, 7 April 2005

Biological E, Intercell tie up on development and marketing

In India, Biological E Ltd. has signed an agreement with Intercell AG for the development, manufacture and sale of the latters Japanese Encephalitis vaccine in Asia. Biological E will be Intercells strategic partner for marketing and selling the vaccine in certain Asian countries. Under the terms of the agreement, Biological E would manufacture the product in India for the Asian endemic market and also file for regulatory approval of this vaccine in India. Intercell AG and Biological E expect to broaden their strategic alliance by collaborating on the development of future vaccines by combining the strength of Intercells Antigen Identification Programme in identifying new, protective antigens with Biological Es experience as a leading Asian vaccine manufacturer.

Intercells product is a purified, inactivated vaccine for active immunization of adults. The vaccine has successfully concluded phase II clinical trials. Biological E is commissioning large-scale cGMP facilities in order to increase its capacity and product range to offer this vaccine on a global basis.

Express Pharma Pulse, 31 March 2005

Jupiter Bio plans to raise US$12 million for peptides expansion

Jupiter Bioscience Ltd. (JBL), India, is to raise US$12 million to fund its expansion plans in the field of peptides. The companys immediate focus will be to commercialize and introduce generic peptide drugs in the domestic and international markets e.g. oxytocin, vassopressin, leuprolide, desmopressin, lisinopril and calcitonin.

JBL was the first company in Asia to introduce and commercialize molecules based on peptide chemistry. Its drugs are applied in the fields of AIDS, CVS cancer and vaccines. The firms United States-based subsidiary is expected to enhance its presence in the peptides and peptide-based drugs business in the global market. Plans are afoot to set up facilities for manufacturing peptide-based bulk actives.

Chronicle Pharmabiz, 24 February 2005


Genome of deadly amoeba exhibits surprising complexity

Researchers led by Mr. Brendan Loftus and Mr. Neil Hall at The Institute for Genomic Research (TIGR), the United States, have found a complex repertoire of sensory genes and a variety of bacteria-like genes in the genome of the parasitic amoeba Entamoeba histolytica. Their analysis reveals the degradation of E. histolytica genome in its transition from a free-living organism into a parasite of the human gut. Evidence found in the DNA sequence indicate that E. histolytica possibly picked up a significant number of its metabolic genes from bacterial co-inhabitants of the human gut. Identification of these genes will shed new light on the unusual shared biology between the parasitic amoeba and anaerobic gut bacteria. Sequencing of E. histolytica was a collaborative effort led by TIGR and the United Kingdom-based Wellcome Trust Sanger Institute.

Another unusual feature of the genome is the presence of an unprecedented number of transfer RNA (tRNA) genes, which constitute nearly 10 per cent of the sequence data collected for the project. These genes appear to be present within the genome in long arrays, the structural or functional significance of which is unknown. According to Dr. Matthew Berriman at the Wellcome Trust Sanger Institute, the genome of E. histolytica offers a fascinating glimpse of how this ancient parasite evolved and highlights unusual metabolic processes that may be exploitable as drug targets. The team also found some large families of surface proteins that may help mediate the amoebas ability to evade the human immune system. It could also enable researchers find better means to harness the immune system to eradicate infection through vaccine development.


Genome map offers first look at human differences

In the United States, a team of researchers led by Mr. David Cox of Perlegen Sciences Inc. reports that the first published genome map of human differences offers a significant step towards truly personalized medicines for individual patients. This project sets a new milestone in the search for genetic elements linked to complex genetic diseases like Alzheimers, cancer and multiple sclerosis. Mr. Cox expressed that the map was adequate to identify some of the most common genetic variations involved in disease.

The key is not to find one or two disease genes but look for patterns that can account for how a person may react to specific high blood pressure drugs, for example. The genomic map was drawn by scanning 71 Americans of African, European and Asian descent, picking out 1.58 million of the most common single-letter variations in the genetic code, called single nucleotide polymorphisms. The map is made up of combinations of nucleotides known as A, C, T and G. Different combinations of these spell out the amino acids, which in turn make up genes and other important genetic areas.


New class of genes determines stem cell fate

Researchers led by Dr. Jon Epstein, a Professor of Medicine at Pennsylvania Universitys School of Medicine, have found a new class of genes known as pangenes that can both govern a stem cells fate and put on hold future differentiation. These few rare stem cells were expressing genes that had earlier been known to be found only in developing embryo. The team found that Pax3, a gene critical in the embryonic development of melanocytes, is also expressed in adult stem cells in the skin. Pax3 plays two seemingly contradictory roles in adult stem cells it directs them to become melanocytes but simultaneously prevents them from differentiating completely.

Dr. Epstein says that this research is conceptually new since a single gene can both tell a cell what it should become and restrict its fate by preventing differentiation. The ability of a single biochemical factor or complex of factors to have this dual capability may represent a general paradigm for the developmental and stem cell biology. Moreover, this new concept could also be important for understanding the cell of origin for a number of tumours. Pax3 is known to be involved in some tumours, which adds evidence to the stem cell origin for some cancers. This theory proposes that many cancers may arise from normally scarce resistant stem cells that grow uncontrollably, rather than from the vast majority of differentiated cells that make up organs where cancers are found. If this theory is correct, resident stem cells in the skin could be the cells that turn into skin cancers like melanoma.

Understanding stem cell biology may therefore be important for developing new therapies for cancer. Adult stem cells have been identified in many types of organs and may be a potential reservoir for tissue generation


RNA interference permanently silences key breast cancer gene

Dr. Ralph Arlinghaus and co-esearchers at the University of Texas M. D. Anderson Cancer Centre, the United States, have developed a way to use RNA interference (RNAi) so that it permanently hampers breast cancer development. This method permanently silences activated STAT3, a crucial gene found in some human breast tumours, thus reducing the cancers ability to become invasive.

The team employed RNAi to knock down gene expressions in a variety of cells and organisms. It works by introducing a small double-stranded RNA that specifically targets a genes product, the messenger RNA. This action then blocks translation and production of the protein that the gene encodes. In the study, researchers used a lentivirus (a type of retrovirus) to deliver a specifically designed long-acting small interfering RNA (termed a short hairpin RNA or shRNA) for mouse STAT3 into a mouse breast cancer cell line. STAT3 was selected since, when activated, it is involved in the formation of multiple types of tumours. When hijacked by a cancer cell, the activated gene is believed to interfere with the ability of key immune cells to attack a growing tumour.

The team used the lentivirus to permanently insert the RNAi into the genome of the cancer cell. After a single exposure of this delivery system, it was observed that 75 per cent of lab breast cancer cells stopped expressing the STAT3 protein. Also, the expression of another protein called TWIST, which is known to be involved in cancer metastasis, was drastically reduced in the STAT3 knockdown cells, thus greatly reducing the ability of these cancer cells to invade normal tissues like the lung.



New mouse model to fight weak bones

In the United States, scientists led by Dr. Mark Hamrick at the Medical College of Georgia have developed a mouse whose large muscles can prevent bone weakening. The animal model has 70 per cent more muscle mass than normal mice as it lacks the myostatin gene, which ensures that muscles do not overgrow. Bones respond to the stress placed on them by extra muscles by forming more bone, thus helping to fight osteoporosis.

According to Dr. Hamrick, bone mass at the end of the pubescent growth phase is a good predictor of an individuals future risk of osteoporosis. The myostatin gene is expressed at its highest level in babies and children, tapering off in adulthood. By knocking out myostatin, researchers were able to study the effect this has on bones to which the muscles are attached. The result was an increase in bone mass.


Breast cancer vaccine gains momentum

In the United States, a team of researchers from the Washington University School of Medicine and the Siteman Cancer Centre, reports to have achieved progress in developing a breast cancer vaccine. The new vaccine comprises copies of the DNA sequence that makes mammaglobin-A, a protein found in 80 per cent of breast tumours in humans. Researchers theorized that the DNA vaccine would rev up special immune cells called T-cells to recognize mammagloblin-A as a foreign molecule when it is displayed on the surface of cells as an antigen, protein fragments produced by invading organisms. The primed T-cells would then proliferate and attack when they meet with mammaglobin-A antigens.

In trials, the team injected the DNA vaccine under the skin of test mice that had been engineered so that their immune systems would react to the human mammaglobin-A like a human immune system. Specific cells in the mice were loaded with mammaglobin-A antigens and it was observed that the vaccine-primed T-cells attacked the loaded cells. The team also transferred vaccine-primed T-cells into mice with growing tumours that had or did not have mammaglobin-A antigens. Tumours with mammaglobin-A antigens stopped growing and shrunk in volume while those without the antigens continued to grow at the normal pace. This vaccine induced immune response could be used to supplement other cancer therapies or immunize high-risk people against cancer.

Express Pharma Pulse, 17 March 2005

Vaccine helps cure TB

Researchers led by Dr. Youngchul Sung at the Pohang University of Science and Technology, the Republic of Korea, report that a tuberculosis (TB) vaccine containing DNA from the bacterium that causes the disease can cure mice when it is combined with drugs. This therapy offers hope for a treatment that works more quickly and effectively than current, drug-only methods.

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, kills about two million people worldwide each year more than any other single infectious disease. Cases began rising in 1985, owing to the emergence of drug-resistant strains and HIV infections; 13 per cent of AIDS deaths are attributed to the disease. Drug-resistant strains emerged partly because patients often fail to complete their therapy. TB can be tackled with a cocktail of antibiotics, but up to 12 months of treatment is essential. In case patients stop taking their drugs too soon, the disease may reappear.

Researchers took TB infected mice and subjected them to the standard drug therapy with or without an experimental DNA vaccine containing two of the microbes genes. In mice given drugs alone, bacterial count increased after the treatment was stopped. Mice treated with the combination therapy showed no such flare-up. In addition, the latter approach triggered an immune response that significantly reduced re-infection. This is the first study showing that a combination of vaccination and drugs can accelerate the disappearance of bacteria as well as protect against re-infection. According to Dr. Dongles Lowrie at the National Institute for Medical Research, the United Kingdom, although the study involved mice, this integrated treatment may get into the clinic faster since with the increasing threat of multi-drug resistant strains, there is a push to get promising therapies into clinical trials.


Cancer vaccine raises immunity while lowering tumour cell count

Researchers headed by Dr. Johannes Vieweg, Associate Professor of Urology and Immunology at the Duke University Medical Centre, the United States, report that a prostate cancer vaccine that trains a patients own dendritic cells to attack a protein antigen expressed by tumours can robustly boost a patients immune system and clinically lower the level of tumour cells in the body. Antigens are protein fragments produced by invaders like viruses or bacteria which trigger attack by the immune system.

The vaccine was developed by isolating dendritic cells from the patients blood. These cells are then treated with messenger RNA that represents the genetic blueprint for telomerase. Telomerase is an enzyme that elongates stretches of DNA called telomeres at the ends of chromosomes. Since the telomere length shortens as cells age, such telomere extension in tumours essentially renders the cells immortal, thus capable of proliferating. Once the dendritic cells have been stimulated with the telomerase RNA, they are injected back under the patients skin where they activate the T cells to attack tumour cells.

Express Pharma Pulse, 17 March 2005

Animal-free stem cells created

A team of scientists led by Dr. Paul de Souza from Rosalin Institute, the United Kingdom, has been able to grow stem cells without using animal products. Normally, embryonic stem cells are grown in feeder layers consisting of material derived from live animal cells. However, there has been concerns that animal products used in stem cell development could contaminate them.

In the new technique, stem cells isolated from embryos were placed on a layer of human protein called laminin, which is the material that separates growing human cells from each other. Nutrients and growth factors were provided using feeder layers from human neonatal foreskin, instead of mouse feeder cells. Four new embryonic stem cells were cultured. Three were given additional growth factors and nutrients derived from cows, as is usual, while the fourth was given a mixture comprising completely of human growth factors and proteins. According to Dr. Souza this is the first embryonic stem cell line not directly exposed to animal products at any stage. However, foreskin cells had been exposed to animal products during their production, which means that there is a possibility that unknown pathogens could be transferred through these helper cells to the stem cells themselves.


Green tea extract has potential as anti-cancer agent

A team headed by Dr. JianYu Rao, an Associate Professor of Pathology and Laboratory Medicine at Jonsson Cancer Centre, the United States, has found how green tea extract works to counteract the development of cancer. Many epidemiologic and animal studies have suggested that green tea extract provides strong anti-cancer effects in several human cancers, including bladder cancer, by inducing death in cancer cells as well as by inhibiting the development of an independent blood supply that cancers develop to facilitate growth.

Cancer grows and spreads when malignant cells move, which is dependent on actin remodelling that is in turn carefully regulated by complex signalling pathways, including the Rho pathway. When actin remodelling is activated, cancer cells can move and invade other healthy cells and eventually other organs. By inducing Rho signalling, the green tea extract makes cancer cells more mature and makes them bind together closely, process called cell adhesion. Both the maturity of the cells and adhesion inhibit the mobility of cancer cells, keeping them confined and localized.
According to Dr. Rao, research was conducted in a carefully controlled cell line environment. However, additional research is necessary to determine exactly how green tea extract functions as a cancer fighter. The next phase of studies would analyse urine from bladder cancer patients to determine the subset of patients who would benefit most from taking green tea extract. The team will also be looking for specific biomarkers associated with actin remodelling and activation of the Rho signalling pathway.


Turmeric can help fight malaria, cancer and HIV

Dr. Govindrajan Padmanabhan and co-researchers from the Indian Institute of Science, Bangalore, India, and researchers at the University of Michigan Medical School, the United States, have exhibited the potential of turmeric as a weapon against malaria. The yellow spice, used in many Indian dishes, has even shown promising effects against HIV and the virus that triggers cervical cancer. Curcumin is the main component responsible for anti-microbial, anti-tumour and anti-inflammatory properties of turmeric. It inhibits drug-resistant forms of Plasmodium falciparum, a parasite that causes cerebral malaria. The team fed curcumin to lab mice infected with Plasmodium bergheii, a related parasite that causes rodent malaria. It was found that the number of parasites in the mices blood decreased by 80-90 per cent. In tests, curcumin completely protected up to 29 per cent of infected mice.

In a separate case study, Dr. Bhupesh Prusty and Dr. Bhudev Das at the Institute of Cytology and Preventive Oncology in New Delhi, India, reported that curcumin could help prevent cervical cancer, which is associated with the human papilloma virus (HPV) in 90 per cent of the cases. The virus has two key genes  E6 and E7, which bind to a protein in normal human cells to make them (the cells) cancerous. Curcumin binds with the same human protein, thereby preventing the virus from attaching to the protein. In laboratory studies, two hours after researchers introduced curcumin into infected cells, the viral genes began to unbind from the human protein. The team plans to start human trials by inserting capsules containing curcumin into the vagina of women infected with HPV daily for 3-4 weeks. The capsules dissolve slowly and release curcumin powder, which will eventually be expelled in urine.

Scientists at the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore fed curcumin to HIV-infected cells in the laboratory. It was observed that the virus stopped replicating. Dr. Tapas Kundu, Associate Professor at the centre, expressed that curcumin stops an enzyme called p300 from performing its normal role of controlling the activity of human genes. Since HIV integrates itself into the genetic material, when p300 stops working the virus can no longer multiply. This mechanism may also explain curcumins other anti-bacterial and anti-viral properties. The p300 enzyme belongs to a class called histone acetylase transferase (HAT) enzymes, which scientists hope would lead them to treatments for a variety of cancers, asthma and neurological disorders.


Genetic link to osteoporosis

A team of researchers headed by Dr. Andi Braun, Chief Medical Officer of Sequenom Inc., the United States, has discovered a genetic variation in the gene encoding phosphodiesterase 4D (PDE4D) that is believed to affect osteoporosis risk. Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in the ageing population. This is the first study to demonstrate that genetic variations in the PDE4D gene family may be involved in human osteoporosis.

Researchers conducted a genome-wide, large-scale study with a set of 25,000 single nucleotide polymorphisms (SNPs) involving more than 600 Caucasian female individuals. The initial association was subsequently confirmed in two large and independent replication studies to validate the initial findings (combined OR=1.7). Additionally, the previously reported bone material density (BMD) association of BMP2, a bone morphogenic protein known to have synergistic effects with PDE4D, was also confirmed in this study. Identification of variations in the PDE4D gene may eventually lead to significantly improved methods for diagnosis, prognosis and treatment of osteoporosis.

Chronicle Pharmabiz, 31 March 2005

New HIV sub-type identified

In India, scientists led by Prof. Uday Kumar Ranga from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) have discovered the presence of a recombinant B-C type of the HIV virus. The molecular laboratory had undertaken a study of 608 samples from 35 towns and cities in Karnataka, Andhra Pradesh, Tamil Nadu and Kerala. The study revealed that sub-type C virus is a dominant form in the country. Over 99 per cent of infections in the country were of this particular virus and it is also responsible for over 55 per cent of infections in the world. Researchers are now investigating into whether sub-type C virus will continue to spread at a faster rate than either sub-type B or A.

Chronicle Pharmabiz, 31 March 2005

Rare human antibody neutralizes most HIV strains

A team of researchers led by Prof. Dennis Burton at the Scripps Research Institute, the United States, has solved the structure of a rare human antibody, which broadly neutralizes the human immune deficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS). The human body creates many antibodies against HIV but they are almost always unable to neutralize the virus. Nonetheless, the immune systems of some HIV patients have beaten the odds and produced effective antibodies. One of these, called 4E10, can neutralize nearly 100 different viral strains of HIV from all over world.

4E10 targets an area on the HIV surface protein, GP41, that the virus uses to fuse its membrane to that of a human cell it is infecting. 4E10s target area is unusually close to the viruss membrane surface and the antibody has a unique adaptation that could help it stick to the virus close to the membrane a finger of amino acids with a propensity to dip down into the membrane and bring the antibody in contact with the target area. The structure of this antibody could be utilized as a template to design an epitope mimic that would stimulate the human immune system to make 4E10 or similar broadly neutralizing antibodies against HIV.



Stat5 protein inhibits spread of breast cancer cells

A research team headed by Dr. Hallgeir Rui, an Associate Professor of Oncology at Lombardi Comprehensive Cancer Centre, the United States, has found that a protein known as Stat5 prevents lab grown breast cancer cells from becoming invasive and aggressive. When Stat5 is active, breast cancer cells are not only less invasive but also aggregate into clusters resembling healthy breast cells. Conversely loss of Stat5 stimulated invasive tumour cell activities.

Stat5 is a DNA binding protein that regulates the expression of certain genes, many of which remain unknown. During pregnancy Stat5 is activated by the hormone prolactin and stimulates the breasts to produce milk. Stat5 remains active in healthy breast cells in non-pregnant women also. However, active Stat5 is lost in many breast cancers, as the tumours become more aggressive and metastatic.

According to Dr. Rui, this research was carried out with cancer cells cultured in the laboratory and additional studies are needed to determine whether Stat5 also inhibits invasion of human breast cancer cells tested in mice. Studies are underway and their outcome would determine whether new therapies could be designed to take advantage of the invasion-suppressive role of Stat5. Since Stat5 is a protein that is located inside the cell, it cannot be administered in the form of an injection to slow down tumour cells. However, Dr. Ruis team is exploring alternate ways of switching Stat5 back on in breast cancer. The new study now provides a mechanism to explain why Stat5 may be a useful tumour marker to predict risk and outcome in early stage breast cancer patients.


New RNA polymerase discovered in plants

Dr. Craig Pikaard and colleagues at Washington University, the United States, have discovered a fourth kind of RNA polymerase, which plays an important role in flowering and DNA methylation, a chemical process essential for an organisms development. The new RNA polymerase, found only in plants, is speculated to have been a plant feature for more than 200 million years. RNA polymerase is an enzyme that is necessary to carry out functions of cells and for expression of biological traits.

Three kinds of RNA polymerases have been known to exist in organisms ranging from brewers yeast to humans. In all eukaryotes, the RNA polymerase Pol I, II and III perform the same distinct, though separate, functions in different species. The team found Pol IV, which originally looked like an alternative form of either Pol I (which makes the largest of the ribosomal RNAs), Pol II (which makes RNAs for protein-coding genes) or Pol III (a specialist in making the shortest ribosomal RNAs and tRNAs).

In a series of genetic and biochemical tests, the team discovered that Pol IV did not share in the duties of Pol I, II or III. However, when Pol IV sub-units were knocked out, the most tightly packed DNA in the nucleus becomes less condensed, small RNAs called siRNAs corresponding to highly repeated 5S rRNA genes and retrotransposons (jumping genes) were completely eliminated and DNA methylation at 5S genes and retrotransposons was lost. Methylation is a vital process involving a chemical modification in cytosine, one of the four chemical sub-units of DNA. Without proper DNA methylation, higher organisms from plants to humans would face a host of developmental problems, from dwarfing in plants to tumour development in humans to certain death in mice. Pol IV helps make siRNAs that then direct DNA methylation to sequences matching the siRNAs.


Protection against cell death during heart attack

At Cincinnati Childrens Hospital Medical Centre, the United States, Dr. Jeff Molkentin and colleagues have discovered that blocking cyclophilin D a member of the immunophilin family of proteins called cyclophilins that bind cyclosporin A in mammalian cells in mice protects the heart from injury due to loss of blood flow during a heart attack. When a person comes to a hospital and it is realized that the individual is having a heart attack or stroke, one of the first things done is to re-establish blood flow. At this point, cells have yet not died, but when flow is re-established there is a huge burst of reactive oxygen, which is when cells die. Dr Molkentins hypothesis is that infusing a cyclophilin D inhibitor at the time when the blood flow is re-established would help protect tissues.

Cyclophilin D, a protein which domiciles in the mitochondria, can be blocked but has never been used in actual patient care. When mitochondria do not function properly, such as when tissue is deprived of oxygen, cells begin to die through a process involving rupture of the mitochondria. When cyclophin D is deleted from mitochondria the cells ability to die is blocked. A class of drugs already exists that block cyclophin D. The most well known is Cyclosporine, used to prevent rejection in organ transplantation.

Express Pharma Pulse, 7 April 2005

New clues to Crohns disease

Researchers at the University of California, the United States, report to have found additional details relating to Crohns disease. People afflicted with Crohns disease experience chronic inflammation, usually of the small intestine, which subsequently results in pain and diarrhoea. The condition is a complicated one and involves genetic, immune system and environmental responses. Crohns disease seems to flare up when immune system cells release excess amounts of cytokines or molecules that attack intestinal cells causing the inflammation.

The team uncovered a nexus between Crohns disease and mutations on the Nod2 gene, one of a family of genes that sense bacterial proteins when they are inside a cell. When the gene detects the bacteria, it sets off the inflammatory pathway in the cell. The protein encoded by Nod2 acts as an early warning system, setting off the bodys defences when something alien like a bacteria or virus enters a cell. When there is a mutation, however, this sensing system fails to detect certain bacteria, enabling the invader to cause infection and inflammation due to problem in signalling. Another team from Yale University report that Nod 2 mutation turns on a chemical that leads to inflammation. This study was undertaken in test tubes, however, and not in mice.



Rice blast genome blasts open rice research

A team of researchers led by Dr. Ralph Dean, a plant pathologist at the North California State University, the United States, has sequenced the genome of the worlds most devastating rice fungus. Magnaporthe grisea is responsible for rice blast, a disease that destroys enough rice to feed 60 million people each year. The team determined that rice blast fungus has over 11,000 genes and its genome code revealed that M. grisea uses a new class of receptor to distinguish its target from other crops. These receptors were found on infectious spores of the fungus, which can aggressively punch into the leaves of rice plants. Researchers reveal that identification of these receptors is a major step on the path to fighting the fungus. Such information could be used to create rice varieties that disguise themselves from these receptors. Genetically engineered rice would reduce the need for toxic chemicals like fungicides for combating M. grisea.


Key molecule identified in plant photo-protection

Researchers led by Dr. Graham Fleming with the United States Department of Energys Lawrence Berkeley National Laboratory and Dr. Kris Niyogi at the University of California-Berkeley (UCB) have identified one of the key molecules that help protect plants from oxidation damage as the result of absorbing too much light. The team determined that when chlorophyll molecules in green plants take in more solar energy than they are able to use immediately, molecules of zeaxanthin, a member of the carotenoid family of pigment molecules, carry away the surplus energy.

Green plants are capable of harvesting energy from the sun and convert it into chemical energy at an energy transfer efficiency rate of approximately 97 per cent through photosynthesis. If scientists could create artificial versions of photosynthesis, the dream of solar power as a clean, efficient and sustainable source of energy for humanity could be realized. A potential pitfall for any sunlight harvesting system is that if the system becomes overloaded with absorbed energy, it is likely to suffer some form of damage. Plants solve this problem on a daily basis with a photo-protective mechanism known as feedback de-excitation quenching. Excess energy, detected by changes in pH levels (the feedback mechanism), is safely dissipated from one molecular system to another, where it can then be routed down relatively harmless chemical reaction pathways. In plants, the light harvesting system comprises two protein complexes, Photosystem I and Photosystem II. Each complex features antennae made up of chlorophyll and carotenoid molecules that gain extra excitation energy when they capture photons. This excitation energy is funnelled through a series of molecules into a reaction centre where it is converted into chemical energy.

Scientists have long suspected that the photo-protective mechanism involved carotenoids in Photosystem II, but until now the details were unknown. UCB researchers used femtosecond spectroscopic techniques to follow the movement of absorbed excitation energy in the thylakoid membranes of spinach leaves, which are large and proficient at quenching excess solar energy. They found that intense exposure to light triggers the formation of zeaxanthin molecules, which are able to interact with excited chlorophyll molecules. During this interaction, energy is dissipated through a charge exchange process wherein zeaxanthin gives up an electron to chlorophyll. This charge exchange brings the chlorophylls energy back down to its ground state and turns the zeaxanthin into a radical cation, which, unlike the excited chlorophyll molecules, is a non-oxidizing agent.

To confirm that zeaxanthin was indeed the key player in energy quenching, and not some other intermediate, researchers conducted similar tests on special mutant strains of Arabidopsis thaliana. These mutant strains were genetically engineered to either overexpress or not at all express the gene psbS, which codes for an eponymous protein that is essential for the quenching process (most likely through binding zeaxanthin to chlorophyll). According to Dr. Niyogi, their work with mutant strains of A. thaliana clearly exhibited that the formation of zeaxanthin and its charge exchange with chlorophyll is the key for the energy quenching measured.

Chemical Weekly, 1 February 2005

Plants engineered to produce edible HIV vaccine

Researchers from Russias Vector State Scientific Centre for Virology and Biotechnology and the Institute for Biological Chemistry and Fundamental Medicine report to have genetically altered tomatoes to prime the immune system against HIV. After HIV was known to cause AIDS in 1984, researchers have learned much about how a vaccine against it might work and believe that by presenting the body with HIV antigens an effective AIDS vaccine could be created. According to the team, though transgenic plants have already been cultivated that carry HIV antigens, they are not edible and could lose some of their therapeutic potential during processing.

To create the tomato variety, researchers used a vector to introduce genes encoding HIV virus proteins. They injected the vector into germinating tomato plants and grew them in a hothouse until they produced fruit. The team then tested the plants and found that the HIV antigen was present in both the leaves and fruits. Tests undertaken to determine if the genetic modification was passed on to subsequent generations revealed that seeds from the original plants also produced transgenic plants, which means that they could be widely dispersed to let people grow their own vaccines.


Mastitis-resistant cows

A team of researchers led by Dr. Robert J. Wall, an animal physiologist at the Biotechnology and Germplasm Lab, the United States, has developed a transgene genetic material using recombinant DNA technology by which cows become resistant to mastitis. Jersey cows were injected with the transgenetic material, which includes the genetic code for producing a naturally occurring antimicrobial protein called lysostaphin. Lysostaphin, when secreted in milk, repels Staphylococcus aureus, a major cause of mastitis.

Three genetically engineered cows have been found to express lysostaphin in their milk and were resistant to S. aureus. No cow has shown any sign of infection even after repeated exposures to S. aureus; in fact, one never became infected, indicating complete protection. Scientists report that this study is very preliminary and none of the milk from the cows will be consumed.


New technique unveiled for gene expression studies

A team of scientists led by Mr. Leon V. Kochian at the Agriculture Research Services (ARS) Plant, Soil and Nutrition Laboratory, the United States, has developed a technique that allows access to immediate data when studying gene expression, without having to go through the slide making process. The old technique involved fixing and dehydrating plant tissue, embedding it in plastic or resin, and slicing it into thin sections, which could then be attached to a slide and labelled with a probe to track molecules.

The new technique involves the use of large plant tissues in gene expression studies, instead of thin sections. In this method, a piece of the target genes DNA is copied and then labelled with a fluorescent compound detectable using a laser scanning confocal microscope. This labelled DNA then binds to the target genes mRNA molecule, so that once sought out and detected, the labelled DNA could give an idea as to where the gene is being expressed. A confocal microscope also works with whole specimens without the need for sectioning.

Agriculture Today, March 2005

ICRISAT starts contained field trials for chickpea

The International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), India, has genetically modified chickpea to be resistant to the pod borer Helicoverpa armigera and has recently launched contained field trails for the crop at ICRISAT-Patancheru. The transgenic chickpea contains Bt genes and will undergo stringent lab and field tests over the next two years. Only after these tests and other clearances are through will the material be transferred for farmers field trials. This transgenic chickpea crop is the third for which contained field trials are ongoing. Transgenic groundnut resistant to the Indian Peanut Clump Virus is being tested since 2002 while transgenic pigeon pea has been through similar trials since 2003.

Agriculture Today, March 2005


Genetic Engineering and Bio-technology: Concepts, Methods and Agronomic Applications

This book is an introductory text to students of genetics and agronomy. The subjects discussed have been grouped under different heads, such as basic concepts of biology, plant biotechnology and genetic engineering, plant biotechnology and bioethics, applications of biotechnology and genetic engineering, plant biotechnology and bioethics, etc.

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