VATIS Update Biotechnology . Sep-Oct 2003

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Biotechnology Sep-Oct 2003

ISSN: 0971-5622

VATIS Update Biotechnology is published 4 times a year to keep the readers up to date of most of the relevant and latest technological developments and events in the field of Biotechnology. The Update is tailored to policy-makers, industries and technology transfer intermediaries.

Co-publisher: Biotech Consortium India Ltd
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Global health challenges flagged for research funding

An international panel of leading health scientists has prepared a list of 14 grand challenges that will form the basis of a research initiative funded by the Bill & Melinda Gates Foundation to address critical scientific challenges that, if solved, could lead to important advances against the developing worlds most pressing health problems. The list includes vaccines that do not need to be refrigerated, staple crops that contain a wide range of nutrients, drugs that minimize the likelihood of drug-resistance, development of technologies that allow patients to be diagnosed for several conditions simultaneously, and the creation of genetic strategies to control disease-carrying insects. The initiatives 20-member panel, which includes several developing country scientists, formulated the 14 challenges from more than 1,000 ideas submitted by individuals from 75 countries. The challenges are divided into seven long-range goals: creating new vaccines; developing childhood vaccines; controlling disease-carrying insects; improving nutrition; improving drug treatments; curing latent and chronic infections; and measuring status of disease and health accurately and economically.

Scientists around the world are now being invited to submit grant proposals for research in the 14 key areas to the US Foundation for the National Institutes of Health, which is running the initiative along with the Gates Foundation. Individual grants will be awarded up to a total of US$20 million for a maximum of five years, and applicants from developing countries are particularly welcomed. The initiative aims to address the issue that only a small fraction of biomedical research efforts are currently directed towards health problems that disproportionately affect the two billion poorest people on Earth.


Southern African nations adopt common GM strategy

At a meeting of the Southern Africa Development Community (SADC) in August 2003 in Dar es Salaam, Tanzania, 14 Southern African nations have agreed on common guidelines for handling genetically modified (GM) organisms and the products resulting from biotechnology. The guidelines are based on the recommendations of a group of 20 scientists, who were sent on a fact-finding mission to the United States and Europe earlier this year. They cover policy and regulations on GM crops and food, as well as the handling of food aid, capacity building and public awareness.

The countries agreed, for example, to try to source food aid from within the region. Food aid containing grain or other plant material that may be genetically modified should be milled or sterilized before distribution, and food aid in transit that contains GM material should be clearly identified and labelled. SADC nations should allocate resources for capacity building in the management of biotechnology and biosafety, as well as develop public awareness on biosafety and biotechnology.

The guidelines state that the region should develop common policy and regulatory systems based on either the Cartagena Protocol on Biosafety or the African Model Law on Biosafety. The African Model Law on Biosafety which was endorsed in the African Union meeting in Maputo, Mozambique, in August 2003 is more comprehensive in its scope than the Cartagena Protocol. For example, it requires countries to seek permission from importing countries before exporting any GM product.

The heads of SADC member states also agreed to develop national biotechnology policies and strategies, and to increase their efforts to set up national biosafety regulatory systems. Member states were urged to sign and ratify the Cartagena Protocol, and to commission studies on the implications of biotechnology for agriculture, environment, health and social-economics.


Asian biotech consortium

An Asian Biotechnology Consortium is proposed to be set up as part of the Asian Cooperation Dialogue (ACD) launched in Cha-am, Thailand, in June 2002. India, through the Department of Biotechnology under the Ministry of Science & Technology, has agreed to take the lead in establishing the consortium to foster cooperation among the ACD countries. Around 22 Asian countries will come together for the consortium.

A two-day meeting of the ACD countries, which concluded in Delhi recently, considered the concept paper prepared by India on the setting up of the consortium as well as modalities of going about it. The meeting recommended setting up of a core fund, and launching of an ACD biotech website to enable the countries of the region to exchange information and take collective action. The meeting agreed to collectively address issues related to the development of biotech infrastructure and expertise, bio-safety, IPR issues, as well as technology access, transfer and commercialization for the socio-economic progress of the region.

Express Pharma Pulse, 16 October 2003

Research community divided over cloning ban

A global treaty seeking to ban human cloning has met with failure after countries failed to agree on whether such a ban should exempt therapeutic cloning, which is the creation of cloned embryos to obtain stem cells for research. A group of 40 countries led by Costa Rica and the United States pushed for a total ban covering both reproductive cloning the cloning of a human to produce another human and therapeutic cloning at talks at the United Nations in New York in September 2003. However, a group of 14 countries, including the United Kingdom, Brazil, China and South Africa, proposed that the top priority should be a ban on reproductive cloning alone. They argued that, given the diversity of views on the morality of therapeutic cloning a technique that could help develop treatments for a range of degenerative diseases individual governments should be left to decide whether or not to permit therapeutic cloning. Over 60 science academies from around the world have called on the United Nations to adopt a ban on human reproductive cloning, but urged against outlawing therapeutic cloning in view of its considerable scientific potential.


HIV vaccine in worldwide trial

The first candidate vaccine against the Human Immunodeficiency Virus (HIV), developed by Merck & Co. Inc. of the United States, is being studied at several locations worldwide. Preliminary results in human tests show that the Merck product has gone farther than any other in generating cellular immune response against HIV. The cellular immune responses refer to the production of cytotoxic white blood cell, known as killer T-cell, which can clear its virus-infected neighbours from the bloodstream. Scientists believe that by speeding up production of these cells, a vaccine may be able to prevent the virus from spreading in the body. Although it may not prevent infection, it might stimulate a response that would prevent the disease that results from the infection.

A goal of the study is a single vaccine that can generate significant immune responses in diverse populations throughout the world. The Phase I trial is designed to test the vaccines safety and ability to stimulate immune responses in healthy, infected volunteers between the age of 18 and 50. Randomly selected volunteers will receive three injections of either the vaccine or an inactive placebo. The study involves 24 clinic visits and 22 blood tests over the course of 18 months.

Express Pharma Pulse, 16 October 2003

CSIR gets patent for fruit fly model to screen plant materials

A United States patent has been granted to Indian scientists associated with the Council of Scientific and Industrial Research (CSIR), the countrys premier research organization, for a novel method of using fruit fly (Drosophila melanogaster) as a model for screening plant materials for their efficacy as CNS stimulant/depressant. The method would help drug research and development programmes. The scientists have successfully tested the extract of several plants, including Acorus calamus, for CNS stimulation/depression activity in the mutant fruit fly D. melanogaster.

The scientists found that the extract of the plant A. calamus decreased the time taken by flies to recover from anesthesia, a state of severe CNS depression, produced by diethyl ether, chloroform and phenobarbital. The extract also increased spontaneous locomotor activity in normal flies an indication that the agent also possesses a property similar to psychostimulants. Thus, the invention covers use of a Drosophila model for in vivo drug screening, testing of plant extracts and finding in the plant A. calamus a substance with analeptic and psychostimulant properties.

Chronicle Pharmabiz, 9 October 2003


Indian President urges efforts for combo vaccines

The President of India, Dr. A.P.J. Abdul Kalam, recently inaugurated a human vaccine manufacturing plant and R&D centre of Indian Immunologicals Ltd. (IIL), a wholly owned subsidiary of National Dairy Development Board (NDDB), at Hyderabad, India. Speaking at the inauguration, Dr. Kalam said there was need for focused clinical research and multi-centric trials to develop a combination of vaccines as part of the immunization programme, as it would greatly reduce the burden on a child who now has to take different vaccines at different intervals. The combination vaccine would require a new delivery system to be developed. He said that food crops have the potential to play a vital role in promoting preventive healthcare by serving as vehicles for production as well as delivery of vaccines.

The new plant and R&D centre were set up with an investment of US$10 million, and have been designed to develop and manufacture various human vaccines including recombinant hepatitis B, measles, diphtheria, pertussis and tetanus. The plant complex has the capability and technology to simultaneously manufacture 200 million doses of each new combination of vaccine per annum.

Chemical Weekly, 14 October 2003

Biocons Rs 500-crore expansion focus on statin

Biocon India will invest over Rs 500 crore (approximately US$103 million) in the next three years on its various expansion projects, changing its profile from a pure biotech company making enzymes into a bio-pharmaceutical firm. The company has acquired 90 acres of land close to its current facility in Bangalore, India. Most of the investment will be for a major expansion of the Biocons statin (a cholesterol-lowering drug) facility and will include fermentation and chemical downstream facilities. Biocon is one of the worlds only two statin manufacturers approved by the United States Food and Drug Authority, the other being Teva Pharmaceutical Industries of Israel.
The company currently has the annual capacity to make 25 tonnes of statin and this is being raised by five times. Worldwide market of statin is worth US$20 billion.

The Economic Times, 30 August 2003

Genentech completes cancer drug filing to FDA

Avastin, a new experimental drug for treating colon cancer, has shown positive results in late-stage clinical trials. The results have prompted the drugs maker Genentech Inc. of the United States to seek a priority review status for this drug. Under priority review, the United States Food and Drug Administration (FDA) would commit to a decision on the drug within six months. In June 2003, FDA put the drug in fast-track, meaning authorities would review data as they become available rather than wait for a complete application. The treatment is potentially the first of a new class of therapies called anti-angiogenesis drugs, designed to stop the blood supply to tumours.

Chronicle Pharmabiz, 9 October 2003

Biogenus showcasing new shrimp culture technology

Biogenus India Ltd. (BIL), a subsidiary of Biogenus Inc. of the United States, has initiated a series of demonstrations of its patented technology for shrimp culture. It has completed a demonstration project at Kunta in Karnataka and initiated another at Nellore in Andhra Pradesh. The company is also establishing a microbiology laboratory at Nellore at a cost of US$100,000. It has made an investment of US$1.5 million in the country.

The companys technology deals with hatchery management, disease and damage control, culture media, farm management processes, pollution control, dissolved oxygen supply management, and DNA probes for virus prediction and analysis. The Kunta demonstration project proved that BILs technology was helpful in maintaining the desired levels of dissolved oxygen, reducing the rate of morbidity and mortality among shrimps, increasing feed conversion ratio and reducing the pollution levels in the effluent water. The application of companys technology would lead to an expenditure of US$10,000 per hectare.

The Hindu Business Line, 11 September 2003

Ranbaxy-Anna University alliance for new drug discovery

In India, an agreement has been signed between Ranbaxy Laboratories Limited, New Delhi, and Anna University, Chennai, in the area of new drug discovery. As per the terms of this agreement, Ranbaxy will fund the Centre for Biotechnology (CBT) at Anna University to screen compounds from natural and synthetic sources for activity in the area of metabolic disorders, urology, and inflammatory and respiratory diseases. It will optimize leads, identify candidates for development and conduct pre-clinical development on leads discovered at Anna University, and will have the option to progress these through IND and clinical development. According to Dr. E. Balagurusamy, Vice-Chancellor of Anna University, the agreement will be a big boost to the Universitys research efforts and an important route to product development in drug discovery programmes.

Chronicle Pharmabiz, 16 October 2003

Human epigenome project to follow EU-pilot study

Epigenomics AG and The Wellcome Trust Sanger Institute of the United Kingdom have signed an agreement to fund and carry out the first phase of the Human Epigenome Project (HEP). HEP will identify and describe human genome sites at which cytosine bases are modified by DNA methylation.

The completion of the human genome sequence has helped scientists to understand increasingly how the changes in DNA sequence in our genetic code plays a role in human health. But human cells have additional layers of gene control and DNA methylation is one of the most important regulators of gene activity. Besides being crucial for normal development, methylation changes are detected in many cancers and some developmental disorders. As DNA methylation is altered in many diseases and is associated with human response to medicines and factors like ageing, HEP is expected to provide a crucial link between genetics, the environment and health. Integration of genetic and epigenetic information will help in understanding how and when genes are switched on or off, which will increase the ability to fight common and complex disease.

Epigenomics will use its expertise in high throughput methylation analysis, while The Wellcome Trust Sanger Institute will contribute high throughput sequencing technology to the collaboration. Tissue samples will be obtained from commercial sources as well as academic partners. Following methylation specific preparation by Epigenomics the samples will undergo sequencing by the Institute.

Chronicle Pharmabiz, 16 October 2003

APIDC-VCL to invest US$1.6 million in biotech firms

APIDCs Venture Capital Fund (APIDC-VCL) based in Hyderabad, India, will be investing US$1.62 million (approximately Rs. 8.1 crore) in the biotech companies Bioserve Biotechnologies, Genomik Design Pharmaceuticals Ltd. and Silico Insights. APIDC-VCL is a public-private partnership between the Ventureast Group and the Andhra Pradesh Industrial Development Corporation. According to Mr. Sarath Naru, Managing Director of APIDC-VCL, the three companies selected for funding are pioneering in using the India advantage, and will have a strong and capable funding team, innovative proprietary technology/processes and a risk-diversified approach with a service and product offering.

APIDC-VCL will select start-up and early-stage businesses such as healthcare, drug discovery, agriculture and dairy. It will normally invest up to 15 per cent, but not more than 25 per cent, of the committed capital in any company. The investment exposure for the invested company would be 2-49 per cent of its total share capital. The fund would normally exit after three years.

Bioserve Biotechnologies, based in the United States, specializes in custom laboratory services, biomedical research and the development of diagnostic reagents. Genomik Design Pharmaceuticals and its parent based in the United States deliver drug design services for drug discovery companies and address niche opportunities. Silico Insights Inc., a United States-India clinical research organization, has developed a proprietary computational platform that identifies disease genes and proteins that may be used as drug targets or as diagnostic markers. APIDC-VCL will invest US$540,000 in each of these firms.

Chronicle Pharmabiz, 18 September 2003


Strand launches research accelerator tool

A new research accelerator called Acuris 1.0, which offers a solution to companies engaged in early stages of drug discovery, has been developed by Stand Genomics, Bangalore, India.

Acuris is an enterprise-wide tool for the automated annotation and management of gene-related data. It gathers, parses, assembles and presents gene-related public information and literature from virtually any public or private source in order to mange collaborative discovery process. The system is designed to be entirely web-based with the server residing at the customer facility for ease of installation, security and fast return on investment. It employs an industry standard three-tier architecture, allowing straightforward integration with existing applications whenever necessary. Its point-and-click screens allow scientists to go from sequence/gene ID submission to visualization and storing of comments and files on their desktop computer, without the need for any special programming knowledge. It runs on Windows, Macintosh, Linux and Solaris operating systems.

Express Pharma Pulse, 18 September 2003

Indias first transgenic green mouse

Scientists at the Indian Institute of Science (IISc), Bangalore, India, have developed an animal model that can be used for conducting cell transplantation studies. They have developed a transgenic green mouse using green fluorescent protein found in jellyfish. According to Prof. P.B. Seshagiri of the Department of Molecular Reproduction Development and Genetics (MRDG) at IISc, there is no need for a fluorescent dye or any kind of tracking mechanism to visualize the green fluorescent protein.

The first transgenic green mouse in the country was developed early this year by the scientists and since then several mouse lines have been generated. When the fluorescent protein is present in cell, the cell will be green. Further, wherever the protein is present, that particular region will also be green. It took about three years to create the infrastructure for the project and several months to generate animals.

Citing an example on how the green fluorescent protein could be used in cell-based therapy, Prof. Seshagiri said that a diabetic patient who could develop resistance to insulin may be administered an insulin-generating cell targeted to reach the pancreas. The fluorescent protein could be used to find whether the cell reached the organ as well as to monitor its progress.

Chemical Weekly, 14 October 2003

Spectrophotometer holds promise in genomics testing

A new technology first developed for use in the DuPont Agricultural Genomics Lab, the United States, promises to make the once hard-to-get genomics information easily accessible with the development of an instrument that can measure nucleic acids in extraordinarily small samples.
Designed to use 1 l samples even high concentration samples without dilution the NanoDrop ND-1000 spectrophotometer now allows measurement of amounts once insufficient for analysis. The capabilities of this compact and inexpensive instrument also ensure that labs do not waste precious, hard-to-obtain samples.

The spectrophotometer is based on a unique, proprietary technology that allows 1 l samples to be pipetted directly onto the measurement surface. Here, using surface tension, a column is drawn between the ends of two optical fibres to establish the measurement path. Describing the method, researcher Mr. Chris Seidel of the Department of Molecular and Cell Biology, University of California at Berkley, the United States, stated that it was as if one were to take a fibre-optic cable, cut it in half, and then pipette some liquid between the two halves. This allows a very small volume of liquid to fit between the severed ends of a fibre-optic cable. The cable then connects a light source to a spectrometer. Since the instrument uses such a minute sample, there is no need for costly disposables such as cuvettes or capillaries and no time is wasted with diluting samples. Further, clean-up takes just a quick swipe with a dry laboratory wipe and the instrument is ready for the next sample.

The spectrophotometer is ideal for learning the dye label concentration of microarray samples, measuring concentration and quality of nucleic acid, and performing full-spectrum UV/Vis spectrophotometry with smaller, safer samples.


First cloned rats born

Scientists at the Institute for Agronomy Research, Jouy en Josas, France, have successfully cloned laboratory rats.

Rats have been difficult to copy. The standard method where adult DNA is injected into an empty egg and then coaxed into life does not work. Once removed from an animal, rat eggs start multiplying before new DNA can be added, with the result that unfertilized cells divide a few times and then die off.

Dr. Jean-Paul Renards team grew rat eggs in a culture dish with a drug that prevents cell division, and then followed the normal procedure. They implanted 130 embryos into two surrogate mothers, yielding two healthy pups. Ralph, the first and the only named rat clone, is now father to a litter of healthy pups. The research illustrates how methodological tweaks can influence cloning success between species. The new trick has worked in one rat strain, but many varieties are used in medical research. According to scientists, it now remains to be seen if this technology is applicable to a wide variety of strains.

Small rodents have been used in medical research for over a century. Mice gained popularity during the 1980s when researchers developed the ability to manipulate the mouse genome at will, resulting in some 5000 GM strains. GM rats can be produced by other methods, but their DNA is altered at random. Cloning gives added control specific genes in the donor cell can be altered, added or removed. Further, genetically modified, cloned rats take much longer to make and suffer more ill health. It is hoped that cloned rats will help scientists unravel the genetics of human disease.



Researchers discover genes that distinguish human and non-human primate brains

In the United States, a team of researchers from the Salk Institute, the Yerkes National Primate Research Centre of Emory University and the University of California-Los Angeles (UCLA) has used gene chips to identify genes in the cerebral cortex that differ in activity levels between humans and non-human primates, including chimpanzees and rhesus monkeys. The researchers identified 91 genes that are expressed in different amounts in humans, compared with other primate species. On further studies, they observed that 83 of these genes showed higher levels of activity in humans, and as a result, regulated neural activity.

When other tissues such as heart and liver were examined, genes showing higher or lower levels of expression were found to be nearly equal in number in humans and non-human primates. The changes in gene activity in the cortex suggest increases in the rate of brain activity, providing a basis for the evolution of the enhanced cognitive abilities in humans. The researchers also found the human brain shows increased expression of genes that protect against activity-related damage. The finding may help explain why humans have the potential to live decades longer than other primates and also why humans are especially vulnerable to age-related, neurodegenerative diseases, such as Alzheimers disease. According to the scientists, the combination of long lifespan and high neural activity makes humans particularly vulnerable to neurodegenerative disease. Furthermore, activity-related damage accumulates with age and has the potential to cause catastrophic breakdown late in life. By understanding how humans protect their brains from activity-related damage, scientists hope to better understand why those mechanisms fail.


Dog genome unveiled

The dog is the latest animal to have its genome sequenced, by a team led by Dr. Ewen Kirkness of the Institute for Genomic Research in Rockville, Maryland, the United States. The genome sequence of the dog, a poodle, will aid the quest to identify human genes and to understand diseases such as cancer, epilepsy, narcolepsy and obsessive-compulsive disorder.

The new sequence reveals that 18,473 dog genes have human equivalents and surpasses the 18,311 known from the mouse sequence. Dogs have 2.4 billion DNA letters, compared with our 2.9 billion, and 39 pairs of chromosomes to our 23. Different breeds are more than 99 per cent identical. The team also found that dogs have many more genes linked to smell than humans. The freely available sequence is less complete than those of mouse and human, and covers about 2 million fragments.
According to researchers, most human diseases have canine counterparts, and dogs are closer to humans than rodents in size, lifestyle and lifespan. There are more than 350 known genetic dog diseases, surpassing all animals save humans. About 10 per cent of Irish setters, for example, carry a gene for an immune disease. DNA testing has allowed breeders to avoid mating carriers. The sequencing of the genome will accelerate the search for such genes.


New insight into the genetics of congenital heart disease 

Scientists led by Dr. Kai Jiao and Dr. Hogan at the at the Cold Spring Harbour Laboratory, New York, the United States, have found that proper expression of a single gene, called Bmp4, is essential for normal mouse embryonic heart development. Even a 50 per cent reduction leads to defects like Atrioventricular Canal Defect (AVCD), which is one of the most common human congenital heart malformations. In its most severe form, AVCD is characterized by a large hole in the wall (septum) that partitions the heart into upper (atria) and lower chambers (ventricles). This defect disrupts the unidirectional flow of blood through the heart, allowing oxygen-rich blood travelling through the left chambers to re-enter the right chambers. The mixture of oxygenated and deoxygenated blood in the right chambers increases the overall volume of blood that the right ventricle must pump to the lungs. This increased blood volume taxes both the heart and the lungs, causing heart enlargement, high blood pressure and, eventually, pulmonary blood vessel damage (i.e. lung disease).

Using a sophisticated approach to alter gene activity in the embryo, the scientists have shown that the reduced expression of Bmp4 may underlie AVCD. It was known that Bmp4 was critical for heart development because it is expressed there at high levels. But the gene is also needed by the embryo very early, before the heart has formed. By knocking the Bmp4 gene out just in the embryonic heart muscle (cardiomyocytes) and leaving it intact everywhere else and by manipulating the system, using conditional tissue specific gene inactivation, the scientists were able to titre down Bmp4 activity to different levels.

A direct correlation was observed between the level of Bmp4 activity and the ability of the septum to correctly partition the upper and lower heart chambers, called atrioventricular septation: the less Bmp4 present in cardiomyocytes, the more severe the septation defect. By varying the level of Bmp4 expression, the researchers were able to recapitulate the entire spectrum of defects seen in AVCD patients.


New method reveals genetic basis of cancer

A powerful new method has been developed for profiling the genetic basis of cancer and other diseases by the scientists at Cold Spring Harbour Laboratory in New York, the United States. The powerful new gene discovery method is called Representational Oligonucleotide Microarray Analysis (ROMA). It detects chromosomal deletions and amplifications (i.e. missing or excess copies of DNA segments), and is useful for a wide variety of biomedical and other applications. By using ROMA to compare the DNA of normal cells and breast cancer cells, a striking collection of chromosomal amplifications and deletions, which are likely to be involved in some aspect of breast cancer, have been uncovered.

Some of the DNA amplifications and deletions detected in this study correspond to known oncogenes and tumour suppressor genes. However, many of them are likely to reveal new genes and cellular functions involved in breast cancer or cancer in general and therefore a genome-wide view of the genetic alterations associated with beast cancers would be provided to researchers.

Express Pharma Pulse, 25 September 2003

Amazons genetic gold

A consortium of 100 scientists working for the Brazil National Genome Project has sequenced the genome of Chromobacterium violaceum, a bacterium commonly found in the Amazon rainforest. The bacterium promises to be a new source of ecofriendly plastic and life-saving medicine. C. violaceum is one of the most versatile and adaptable micro-organisms, and dominates a variety of ecosystems in tropical and sub-tropical regions. The research on C. violaceum started some 30 years ago and in 1978, scientists found a pigment called violacein, which can cure certain skin diseases. In December 2000, Brazilian scientists also unravelled that the pigment has therapeutic properties against several kinds of cancer, tuberculosis and the deadly chagas disease a tropical disease caused by Trypanosoma cruzi, a protozoan that attacks the vital organs that plagues may parts of Latin America. The bacterium is the first project of the Brazil National Genome Project, involving some 25 laboratories located in Brazil.

Besides the gene sequence that codes for the violacein, the scientists have identified some other useful genetic materials such as the genes that order proteins to naturally break down gold, act as potential biocontrol agents against insects and fungi and fight arsenic pollution. Several other genes code for proteins that synthesise compounds with antibiotic properties and phenazine, a substance known to have properties to arrest the replication of tumour cells. Genes that have the capacity to synthesise polyhydroxyalkanoate polymer, which has physical properties similar to propylene, have also been identified. This makes the bacterium an important renewal source of biodegradable plastic.
The scientists hope that the sequencing of more such similar, free-living tropical bacteria could lead to the production of industrially useful genes, enzymes and secondary metabolites, which would benefit the biotechnological and pharmaceutical industries in the developing world and would also be a stimulant to preserve ecosystems where such organisms are found.

Down To Earth, 15 October 2003


Two mechanisms for immune system cells differentiation

Dr. Nancy Manley and her co-researchers at the University of Georgia, Atlanta, the United States, have found that differentiation of cells in the immune system is by two mechanisms controlled by a genetic switch. Clues to this genetic switch were found using the thymus, a glandular structure behind the top of the sternum, where disease-fighting T-cells mature. T-cell count is a relative indicator of the bodys ability to fight disease, especially in AIDS patients. The finding could help find ways to restart T-cell production in older adults and victims of diseases such as AIDS. The results are also significant in stem cell research, as it is important to know how to control their growth and development to allow the production of specific mature cell types in the lab.

Researchers have known for years that a gene called nude which causes mice to grow without hair of any kind is also involved in immune response. In the nude mouse, thymic epithelial cells (TECs) specific thymus cells required for T-cell maturation fail to grow and mature. As a result, no T-cells are made and these mice cannot ward off diseases. However, in a mutant mouse made in Manleys lab, the abnormal thymus did produce T-cells, although in greatly reduced numbers. It turned out that the initiation and progression of TEC growth are genetically separable functions in the new mutant mouse. In addition, this also provided the first genetic evidence that an already-known process called cross-talk is needed for the growth of the TECs.


Drugs for blood pressure effective in malaria control

In the United States, a team of researchers led by Prof. Kasturi Haldar at the Feinberg School of Medicine of Northwestern University, Chicago, has found that hormones that regulate cardiovascular function also influence malaria infection. Hence, beta-blockers safe, inexpensive and commonly prescribed drugs used worldwide to treat high blood pressure are effective against the deadliest and most drug-resistant strain of malaria parasites such as Plasmodium falciparum.

Rather than targeting the parasite that causes malaria, an approach that has resulted in mounting resistance to many anti-malarial drugs, Haldar and co-researchers focused on identifying and blocking the process by which red blood cells allow parasite entry. The researchers found that a G protein subunit, called Gs, concentrates around the malaria parasite during infection of the red blood cell. G proteins are essentially transducers, which translate signals from hormones, neurotransmitters and other substances to activate cell processes. Using special peptides that inhibited the interaction of Gs protein, they were able to show in several laboratory models of malaria that blocking the Gs signals resulted in decreased malaria infection. Two major receptors associated with Gs, the beta-adrenergic and the adenosine receptors, are present in red blood cells. Beta-receptor antagonists prevented P. falciparum from entering red blood cells by interfering with the lock-and-key interaction of Gs with its receptors on the cells surface.


Revolutionary medicine tested

A new therapy has been pioneered by scientists led by Dr. Lother Steidler at the University of Cork, the United Kingdom, wherein bacteria have been genetically modified (GM) to act as drugs within human bodies. The organisms are designed to treat inflammatory bowel disease by producing a human immune protein that dampens inflammation. Patients take the bacteria as a coated pill that protects them in stomach till it breaks open and ejects its live cargo in the small intestine and colon. Steidlers team chose the Lactococcus lactis bacterium since it is already consumed in dairy products such as cheese. A gene producing the human immune protein interleukin-10 was used to replace a key bacterial gene called the thyA, which codes for the enzyme needed to make thymidine, a building block of the bacteriums DNA.

GM bacteria are widely used to make food and drugs, but the prospect of drug-producing gut bacteria getting into the wrong people or swapping genes with other bacteria has been the concern of many. To address such fears, the bacteria have now been altered so that they die within days when discharged into the environment along with feces. In the gut, thymidine is released when food is digested, and therefore the modified bugs can flourish there even though they cannot make the enzyme. Outside the gut, the bacteria die of lack of thymidine. It is also unlikely that the bacterium will acquire a copy of thyA from other bacteria, because the gene is found on the main bacterial chromosome, rather than on the plasmids that bacteria swap freely. One concern though is that there is no way to control the distribution of the bacteria within the gut, or how much interleukin-10 is produced.

Down to Earth, 15 August 2003

Hormone melatonin may be factor in nocturnal asthma

A research team led by Mr. E. Rand Sutherland from the National Jewish Medical and Research Centre in Denver, the United States, has found that the hormone melatonin may be a factor in the worsening of nocturnal asthma. Nocturnal asthma, also referred to as sleep-related asthma, is characterized by increased airway inflammation during the hours of sleep, with symptoms the worst from midnight to 4 a.m. Melatonin, a hormone produced by the pineal gland, is a regulator of the bodys circadian rhythms, such as eating or sleeping.

The team investigated the relationship between melatonin and severity of nocturnal asthma by evaluating 24-hour melatonin level in a test group consisting of healthy people, and nocturnal and non-nocturnal asthmatics. It found that nocturnal asthmatics have melatonin levels that are significantly higher than healthy subjects and that higher melatonin levels are associated with severe nocturnal worsening of asthma.

Chemical Weekly, 14 October 2003

Botox eases chronic pain

Researchers led by Dr. Keith Foster at the Centre for Applied Microbiology and Research near Salisbury, the United Kingdom, have discovered that the most potent neurotoxin and a protein from Mediterranean coral tree (Erythrina cristagalli) could be combined for treating the chronic pain that afflicts millions of people.

Botulinum toxin, better known as Botox, is also used to treat an increasing range of medical conditions. Botox, whose effects can last for months, works by blocking the release of the neurotransmitters that relay the contact now message from nerves to muscles. The machinery that is knocked out is actually found inside most cells, but the toxin only affects the neurons that control muscles. This is because of a targeting sequence in the toxin that permits it to bind only to muscle cells.

The scientists looked for a targeting sequence specific to the nerves that transmit pain signals so that this sequence could be used to turn the neurotoxin into a painkiller. It was found that the coral tree protein binds to the surface of pain neurons and no other cells. Since pain nerves do not carry any other sort of message, the altered toxin stops pain without affecting the senses. In three experiments on mice, the painkiller performed as well as morphine at preventing pain and it was still working nine days later, whereas morphine would have worn off after about four hours. The team is now preparing for initial trials of the drug.

Chemical Weekly, 7 October 2003

Combined effect of proteins saves lives in pneumonia

A new research, which suggests that two different proteins work together to provide an effective host defence to the most prevalent form of pneumonia, may lead to new treatments against the disease. Dr. Anita Rijneveld from the University of Amesterdam, the Netherlands, infected mice with bacterium Streptococcus pneumoniae, which causes more than half of all bacterial pneumonia, and studied the inflammation process in the lungs during the infection. She also studied the inflammatory responses by examining mouse lungs for the presence of cytokines, small proteins that function as messengers in the immune system. They coordinate the inflammatory response by recruiting white blood cells against the bacteria.

Dr. Rijneveld used mice without the receptor for the cytokine interleukin I (IL-1), which is necessary for the immune response during the first phase of the pneumonia. She discovered that in addition to IL-1, the cytokine tumour necrosis factor-a (TNF-alpha) is also important for the survival of mice with bacterial pneumonia. If TNF-alpha is inhibited in ill mice without IL-1, all those mice die.

Chemical Weekly, 7 October 2003


TCS develops multi-functional bio-suit

Tata Consultancy Services (TCS) is currently testing the beta version of a comprehensive, scalable software suite called Bio-Suite. The product would be launched by the end of this fiscal year. The software product, being developed as part of the Rs 15 crore (approximately US$3.3 million) New Millennium Indian Technology Leadership Initiative project, is sponsored by the Council of Scientific and Industrial Research (CSIR) in association with 18 research and academic institutions in India.

The software suite can be used for genome analysis, sequence analysis, 3D modelling, simulation, manipulation, structural changes, drug design, pathway modelling, SNP analysis and comparative genomics. It runs on platforms such as Compaq, IBM Aix, SGI, Linux clusters and the operating systems of Unix and Linux flavours. The software comes equipped with 3D structure manipulations, which will help in building molecules, side chain placements and stereo chemical editing, while the drug design model will help in developing de novo designs with high throughput screening of chemical databases. While the market for the software is estimated at around US$250 million, the market for service is put at US$1.5 billion or more.

The Financial Express, 3 September 2003

Researchers stretch DNA on silicon chip

Researchers at Purdue University, Indiana, the United States, have precisely placed DNA strands on a silicon chip and stretched them out to enable more clear reading of their encoded information. These two steps are possibly critical to using DNA in future electronic devices and computers.
The researchers created templates containing positively charged lines of a commercially available polymer so that when the negatively charged genetic material is dropped onto the chip, it gets attracted to the lines. Then the researchers used a syringe to drag the DNA, uncoiling the strands along the template surface. They made use of an instrument called an atomic force microscope and a cantilever device to lay down the lines of polymer in a process called dip-pen nanolithography. Each of the lines of polymer is about as wide as 100 nm, and each chip of 1 cm2 contains numerous templates. A single DNA molecule is about 2 nm wide. The same technique can be used to precisely place a variety of biological molecules, including proteins and viruses, onto such templates. They can be kept in their natural state and still function as they would in living organisms.

Although other researchers have deposited DNA onto similar templates, this research is the first to demonstrate how to also stretch strands of DNA in specific locations on such templates, which contain features so small that they are measured in nanometres. This step could lead to the ability to stretch DNA molecules in specific locations on electronic chips, which is critical in harnessing the storage capacity of DNA for future computers. Researchers also would like to be able to place DNA strands directly between two electrodes to perform consistent, precise measurements and determine certain electronic characteristics of genetic material.

Theoretically, future computers might tap the vast storage capacity that enables DNA to hold the complex blueprints of living organisms. These new computers would be based on DNAs four-letter code instead of a computers customary two digits, and would offer advantages in speed, memory capacity and energy efficiency over conventional electronics for solving certain types of complex problems.

Contact: Dr. Albena Ivanisevic, Purdue University, Indiana, United States of America. Tel: +1 (765) 496-3676;




China takes centre stage for liver proteome research

The Human Proteome Organization (HUPO), an international group that is overseeing plasma and brain proteome projects, has taken an initiative to describe all the liver proteins. China will coordinate liver proteome activities in up to 20 countries including Canada, France and the United States. The project aims to identify the multitude of proteins that are expressed in the human liver. It will also collect information about their concentrations in normal and diseased states, where they are localized within the liver, which other proteins they interact with, and whether they exist in various chemically modified forms. The pilot phase of the study has already begun, and China has pledged US$24 million for the three-year pilot phase.

By the end of 2005, the projects planners hope to have data on some 3,0005,000 liver proteins and by 2010 they hope to have pinned down 10,000 proteins. The research group intends to make antibodies against 5,000 proteins by the end of 2005, using a technique considered to be apt for large-scale analysis. Conventionally, antibodies are made one at a time, but the Chinese team will inject several different proteins extracted from human livers into mice and then harvest the antibodies made to each of them from the mices blood. These antibodies will be identified individually by identifying the specific protein to which each binds.


New insights into genes transcription factors

A team of researchers led by Dr. Anna Mapp of the University of Michigan, the United States, has gained important insights into the workings of gene activating transcription factors, using a new approach for developing artificial transcription factors (ATFs). Transcription factors occur naturally in cells, but researchers have been working to develop ATFs that can be tailored to regulate particular genes or sets of genes. These molecules can help scientists probe transcription, the first step in the process through which instructions coded in genes are used to produce proteins. Error in transcription are linked to diseases ranging from diabetes to cancer. ATFs eventually might also be used to correct those mistakes.

The team discovered that the gene-activating power of a transcription factor depends on where the factor binds onto the cells transcriptional machinery, as well as on how tightly it binds. Previously, researchers had thought that binding affinity (tightness) was the main determinant of a gene activators potency. Natural transcription factors typically have two essential parts or modules: a DNA-binding module that homes in on the gene to be regulated, and a regulatory module that attaches itself to the cells transcriptional machinery through a key protein-to-protein interaction and activates or represses the gene. The team first isolated and purified a protein from the cells transcriptional machinery. Then they screened large groups of synthetic peptides (short chains of amino acids) for their ability to bind to the protein.

Express Pharma Pulse, 25 September 2003

New protein provides clues for diabetes drugs

A new study conducted at Whitehead Institute for Biomedical Research, Boston, the United States, has found a protein that plays an essential role in regulating a cells ability to absorb glucose an important step towards gaining a better understanding of the underlying causes of diabetes.

The causes for Type 2 (adult-onset) diabetes, a disorder in which cells lose their ability to absorb glucose from blood, and how the process works in normal cells are not known, according to Dr. Jonathan Bogan, lead author of the paper and an assistant professor at Yale University, School of Medicine, New York. Key to this are glucose transporters, a class of proteins that shuttles glucose molecules through the membrane and into the body of the cell. Among the several known glucose transporters, GLUT4 is the only transporter that responds exclusively to the presence of insulin. GLUT4 is usually deep inside the cell, moving to the surface only when insulin sends a signal.

Dr. Bogan engineered GLUT4 proteins so that they had two distinct fluorescent tags, and studied them in cultured fat cells. One tag glowed only when GLUT4 appeared at the cell surface; the other was detectable at any location in the cell, enabling Dr. Bogan to measure GLUT4 distribution within the cells. A collection of approximately 2.4 million proteins was tested to see which ones had an effect on GLUT4 distribution. They found that one protein, TUG, had a significant effect on GLUT4, acting as a tether that binds GLUT4 inside the cell. When insulin reaches the cell surface, it signals TUG to release GLUT4, which then moves to the cell surface to allow glucose absorption. These results suggest that excess tethering may somehow contribute to insulin resistance. According to Dr. Harvey Lodish, co-author of the study, the discovery of this key component of the GLUT4 pathway is a significant clue for possibly identifying a diabetes drug target.


Comprehensive view of protein activity in higher organism

The first comprehensive view of protein activity in higher organisms has been provided by scientists at the University of California-San Francisco (UCSF), the United States. The powerful tools developed allow researchers to look in unprecedented detail at the thousands of proteins acting and interacting in a living organism.

The UCSF scientists were able to examine thousands of proteins individually one in each of thousands of different strains of Saccharomyces cerevisiae, the common bakers yeast. About one-third of the yeasts genes are shared by humans. The scientists used two identical sets of thousands of strains of the yeast: one to determine where in the cell each protein acts, and the other to determine the abundance of each protein. To study each proteins cellular locale, they tagged a different gene in each yeast strain with a green florescent marker. When the gene instructed a living cell to make a specific protein, that protein glowed green and could be located in the cell using microscopy. Since each yeast strain had only one tagged protein, the researchers could easily pinpoint the location of nearly all of the organisms proteins.

The new approach was far more sensitive than any previous attempt to detect low levels of protein activity. They detected proteins in quantities as low as 50 molecules per cell and as high as a million or more molecules per cell, demonstrating million or more molecules per cell, demonstrating that living cells utilize different proteins in vastly different amounts.


Clinical proteomics promises improved disease diagnosis

According to a recent study by BioInformatics LLC based in Arlington, Virginia, the United States, clinical proteomics stands to revolutionize the huge clinical testing market. Cancer and infectious diseases are two conditions believed to be the best candidates for prognostic or diagnostic assays based on protein-profiling.

Clinical Proteomics: A First-Glance Market Report, based on a detailed survey, provides the thoughts of more than 300 proteomic researchers on disease applications, assay formats and technical standards for protein-profiling assays that will be used for disease prognosis or diagnosis in a clinical setting. Other applications include antibiotic and drug sensitivity profiling, monitoring stress and cell death pathways for toxicology purposes, and measuring protein expression patterns that are characteristic of a variety of maladies.

Many researchers believe that changes in protein expression patterns are the most accurate way to identify diseases in their early stages and to determine the most effective courses of treatment rather than focusing on genetic alterations that may lead to a particular disease. Over 40 per cent of scientists perform protein-profiling with the objective of identifying protein expression patterns associated with diseases. Further, in contrast to existing diagnostic assays, which examine protein biomarkers one at a time, clinical proteomics is based on creating protein profiles that simultaneously detect hundreds or even thousands of proteins in a single assay enabling much higher levels of prognostic or diagnostic accuracy.

According to the study, the future of clinical proteomics lies in two technologies: mass spectrometry and protein arrays/chips. Although protein-profiling is now used for a variety of research applications, it has not yet been adopted as a routine clinical testing method. This could be due to lack of ample reference databases for disease biomarker evaluation, difficulty in obtaining clinical samples and the sample quality.



Scientists clean up arsenic with GM plants

Scientists at the University of Georgia, Athens, the United States, have genetically engineered plants to remove the pollutant arsenic from the soil. The findings could help to combat arsenic poisoning which causes skin, lung, kidney and liver cancers and damage to the nervous system especially in countries where millions of people are at risk through drinking contaminated water.

The researchers inserted two genes from the bacterium Escherichia coli that allow the common weed Arabidopsis thaliana to tolerate arsenic, which is usually lethal to plants. As a result, instead of dying from exposure, the genetically modified A. thaliana is able to take up arsenic from the soil and transport it to its leaves. This new system could be a major step in developing methods of cleaning up the environment using plants.

The researchers say that the plants genetically engineered to remove arsenic in this study are ready for use in the field, but expect to make significant improvements in the amount of arsenic that can be extracted through future experiments. They also expect that this new system should be applicable to a wide variety of plant species, and are already working on putting the genes into cottonwood trees, which have a large root system and could be particularly effective in removing arsenic from the soil.


Potato culture may make bio-pesticide growth cost-effective

Scientists working at the Centre for Research in Medical Entomology of the Indian Council of Medical Research in Madurai, Tamil Nadu, have developed a potato-based culture for the mass production of bio-pesticides. The team led by Dr. S. Poopathi explored the use of several less expensive culture media (potato, common sugar and Bengal gram) for the growth and production of Bacillus thutingiensis subsp. israelensis (Bti), since the production of Bti as a bio-pesticide is not cost-effective using existing fermentation technology.

Growth was obtained in all tested media and was comparable to that obtained in conventional Luria-Bertani medium. Toxicity assays showed that the toxin produced from the novel growth media were effective in killing the larvae of Culex quinquefasciatus, Anopheles stephensi and Aedes aegypti, and toxicity was comparable to that produced from Luria-Bertani medium. These observations suggest that potato can be used as an economical source of culture medium for the production of Bti toxin in mosquito control programmes.


Biologists solve mysteries of photosynthesis and animal metabolism

A team of scientists at the Purdue University, the United States, led by Prof. William Cramer from Purdues School of Science, have obtained a complete molecular-scale picture of how plants convert sunlight to chemical energy, offering potential new insights into animal metabolism as well.

Using advanced imaging techniques, the team determined the structure of cytochrome, a protein complex that governs photosynthesis in a blue-green bacterium. The work reveals a wealth of information not only about a chemical process crucial to all life on the planet, but also about how plant and animal cells handle and distribute energy. The study is also an important contribution to the young field of proteomics research because there is little data on the important family of membrane-embedded proteins in the total protein database.

Membrane proteins are involved in a cells interactions with its environment, making them an essential component of metabolism. While proteomics specialists have been crystallizing protein molecules for years to obtain their structure, membrane proteins have proven difficult because they do not dissolve in water, a crucial step in the crystallization process. Prof. Cramers team was successful in crystallizing membrane proteins earlier this year.

According to Dr. Janet Smith, the team member responsible for much of the structure analysis, plant cell membranes are like the two ends of a battery. They are positive on the inside and negative on the outside, and get charged up when solar energy excites electrons from hydrogen within the cell. The electrons travel into the cell membrane via proteins that conduct them just like wires. Because of their high energy level, the electrons want to fall back, releasing the energy a plant harnesses to stay alive. While this general picture has been common knowledge to scientists for decades, the complex motion of electrons and protons in the membrane has not been so. Through this study, it has been possible to see how the membrane uses the motion of the electrons to drive the cells metabolism.

The cell that provided the proteins for the teams work was a cyanobacterium, a single-celled thermophile plant, isolated by Swiss researchers at a hot spring in Iceland. While animals do not use photosynthesis, their cells do make use of similar proteins for respiration. The similarities could lead to a better understanding of our own metabolic processes. The team is hopeful that their method can be applied to other membrane proteins, which they consider a variety of vast untapped potential.


New gene for plant growth and development discovered

A team of biologists at the University of California-San Diego (UCSD), the United States, and colleagues at other institutions have jointly found a new gene essential for plant growth. Using a new approach known as chemical genetics, in which chemicals are used to regulate activities of proteins produced by specific genes, the team discovered a previously unknown gene SIR1 which functions to keep the effects of auxin in check. Auxin plays important roles in the development of roots, stems and leaves. The scientists say that one implication of their discovery is the potential development of environmentally safe herbicides from chemicals that impede the action of auxin by over-activating the SIR1 gene.

The researchers found that if, at different times, they applied and withdrew the chemical that inactivated the SIR1 protein, this led to strangely shaped plants because SIR1 usually dampens the effect of auxin. Too much or too little auxin interferes with development, and scientists think that this could have implications for the design of novel flowers and other plant structures.



A Practical Guide to Containment Greenhouse Research with Transgenic Plants and Microbes

This 60-page guide is intended as a simple and convenient reference on appropriate biosafety and containment levels for GMO research conducted in greenhouses. It will help clarify what level of containment is needed and what measures are sufficient to achieve the various biosafety levels.

Proceedings of a Workshop on Criteria for Field Testing of Plants with Engineered Regulatory, Metabolic and Signaling Pathways

This two-day workshop brought together regulators and industry and academic scientists to discuss and evaluate current knowledge and research on secondary effects of transgenes that function as transcription factors, in signal transduction or to modify metabolic pathways. It focused on commercially promising case studies to promote information exchange. The workshop proceedings would be valuable to those who develop commercial products or make regulatory decisions in this field.

For the above publications, contact: Information Systems for Biotechnology, Virginia Tech, 207 Engel Hall, Blacksburg, Virginia VA 24061, United States of America. E-mail:

Biotechnology: Applications and Career

The book addresses the young aspirants willing to make their careers in this upcoming area of science. Brief treatments of different branches of biotechnology including plant, animal, medicine, marine, bioinformatics, environment and industrial are provided for guidance, together with exhaustive lists of institutes, references and websites.

Contact: Mr. Vinod Vasishtha, Viva Books Pvt. Ltd., 4262/3, Ansari Road, Daryaganj, New Delhi 110 002, India. E-mail:


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