Rajiv Gandhi Center for Biotechnology

Thiruvananthapuram, India

Rajiv Gandhi Center for Biotechnology

Thiruvananthapuram, India

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News Article | April 19, 2017
Site: www.biosciencetechnology.com

Frog mucus is loaded with molecules that kill bacteria and viruses, and researchers are beginning to investigate it as a potential source for new anti-microbial drugs. One of these "host defense peptides," courtesy of a colorful tennis-ball-sized frog species (Hydrophylax bahuvistara) from southern India, can destroy many strains of human flu and protect mice against flu infection, researchers report April 18 in the journal Immunity. This peptide is far from becoming an anti-flu drug, but this is the first evidence of its flu-killing ability. It seems to work by binding to a protein that is identical across many influenza strains, and in lab experiments, it was able to neutralize dozens of flu strains, from the 1934 archival viruses up to modern ones. The researchers named the newly identified peptide "urumin," after the urumi, a sword with a flexible blade that snaps and bends like a whip, which comes from the same Indian province, Kerala, as the frog. "Different frogs make different peptides, depending on where their habitat is. You and I make host defense peptides ourselves," said flu specialist and study co-author Joshy Jacob of Emory University. "It's a natural innate immune mediator that all living organisms maintain. We just happened to find one that the frog makes that just happens to be effective against the H1 influenza type." Practically all animals make at least a few anti-microbial host defense peptides as part of their innate immune systems, and researchers are only beginning to catalog them. However, frogs have drawn the most attention as a source of host defense peptides, because it's relatively easy to isolate the peptides from their mucus. Researchers can simply give the frogs a small electric shock or rub a powder on the frogs to make them secrete their defense peptides, which can then be collected. Researchers from the Rajiv Gandhi Center for Biotechnology in Kerala, India, have been isolating peptides from their local frogs and screening them for potential anti-bacterials, but Jacob wondered if there might also be peptides that neutralize human-infecting viruses. Jacob and his colleagues screened 32 frog defense peptides against an influenza strain and found that 4 of them had flu-busting abilities. "I was almost knocked off my chair," said Jacob. "In the beginning, I thought that when you do drug discovery, you have to go through thousands of drug candidates, even a million, before you get 1 or 2 hits. And here we did 32 peptides, and we had 4 hits." Unfortunately, when the researchers exposed isolated human red blood cells (in a dish) to the flu-buster peptides, three out of the four proved toxic. However, the fourth--urumin--seemed harmless to human cells but lethal to a wide range of flu viruses. Electron microscope images of the virus after exposure to urumin reveal a virus that has been completely dismantled. Jacob's team is still working out the details of the flu-destroying mechanism, but the urumin appears to work by targeting a viral surface protein called hemagluttinin, the H in H1N1. "The virus needs this hemagglutinin to get inside our cells," said Jacob. "What this peptide does is it binds to the hemagglutinin and destabilizes the virus. And then it kills the virus."


News Article | April 18, 2017
Site: www.latimes.com

What’s more amazing than kissing a frog and getting a handsome prince? How about scraping off a bit of the mucus layer that covers his skin and finding in it a potent weapon against influenza? That, quite simply, is what scientists from Emory University appear to have done in discovering an antimicrobial peptide on the skin of Hydrophylax bahuvistara, a species of frog native to southern India. What they found could treat a relentless scourge of humankind that kills as many as half a million people around the world each year. There, in the film of secretions that protects the frog’s skin from deadly pathogens, scientists have identified a string of amino acids that completely destroys a wide swath of influenza A viruses while doing no harm to healthy human red blood cells. This discovery, reported Tuesday in the journal Immunity, will face many hurdles before it can become an actual influenza treatment. But its novelty is a potential source of strength against flu viruses that have begun to develop resistance to existing antiviral medications. Each strain of the flu is named for its particular combination of two surface proteins, hemagglutinin (of which there are 18 known varieties) and neuraminidase (of which there are 11). The most common form of seasonal influenza has the H1 version of hemagglutinin (along with the N1 version of neuraminidase); in laboratory experiments, the frog peptide wiped out every type of H1 flu that was tested. The current version of H1N1 flu came on the scene in 2009 with the H1N1 “swine flu” pandemic that combined viruses from pigs, birds and people. When the virus first emerged, humans had limited immunity against it, but public health measures and good luck conspired to protect us from disaster. Scientists fear that, in the absence of a wide-spectrum weapon against flu, we won’t be so lucky next time a new strain appears. There’s no shape-shifting prince in this story, but there is a sword: the Emory team has dubbed the virus-killing peptide “urumin.” That moniker is derived from the word urumi, the deadly three-pronged ribbon sword used by skilled practitioners of Kerala Kalari Payat, sometimes called the “mother of all martial arts.” Kalari warriors, who would wear this fearsome weapon around their waists, originated from the same province in Southern India that is the native habitat of Hydrophylax bahuvistara. The discovery is a reminder of the value of preserving biodiversity as a source of inspiration for new human drugs. To protect themselves in a soup of potentially dangerous microbes, many plants and animals — including frogs — coat themselves with “host defense peptides.” Those peptides have led to the discovery of many antibiotic agents, which is why researchers from the Rajiv Gandhi Center for Biotechnology in Kerala, India, have been swabbing the skins of local frogs and screening these samples. The study’s lead author, Emory flu expert Joshy Jacob, wondered if the frog mucus might also contain peptides that could neutralize viruses that attack humans. In what is normally an exhaustive process of sifting, Jacob and his team started by screening 32 peptides against a strain of influenza. To his astonishment, the team immediately found four peptides that attacked influenza. Urumin was the only one that did so without inflicting collateral damage on healthy human cells. After isolating urumin, the researchers sequenced the genome of their find. Then they chemically synthesized it. Testing this agent in human blood samples infected with influenza A virus, they found that it seemed to home in on the hemagglutinin protein. "What this peptide does is it binds to the hemagglutinin and destabilizes the virus,” Jacob said. ”And then it kills the virus." By targeting a protein that is common across many different flu strains, the frog peptide behaved like a universal flu vaccine. Indeed, urumin neutralized dozens of flu strains, ranging from viruses that circulated in 1934 right up to modern ones. It was also effective at destroying H1 influenza A viruses that had developed resistance to antiviral medications. Current drugs used to blunt the attack of many flu viruses target the neuraminidase protein. But these drugs — including zanamivir, oseltamivir, peramivir and laninamivir — are quickly thwarted when neuraminidase mutates. Urumin was not so easily put off because it focused on the hemagglutinin protein instead. Having effective antiviral medications is especially important when a flu strain emerges before a vaccine can be formulated to protect against it. In these cases, giving drugs to people after they’re infected can make infections milder and shorten the time an infected person is sick. It may even make the virus less likely to spread to others. For Jacob and his team, the next step will be to test urumin in animals of increasing complexity, even as they deepen their understanding of exactly how it works. Exercise can be contagious, new social network analysis finds Why doctors are being urged to join the March for Science on Saturday What would make a computer biased? Learning a language spoken by humans


News Article | April 18, 2017
Site: www.rdmag.com

A component of the skin mucus secreted by South Indian frogs can kill the H1 variety of influenza viruses, researchers from Emory Vaccine Center and the Rajiv Gandhi Center for Biotechnology in India have discovered. Frogs' skins were known to secrete "host defense peptides" that defend them against bacteria. The finding, scheduled for publication in Immunity, suggests that the peptides represent a resource for antiviral drug discovery as well. Anti-flu peptides could become handy when vaccines are unavailable, in the case of a new pandemic strain, or when circulating strains become resistant to current drugs, says senior author Joshy Jacob, PhD, associate professor of microbiology and immunology at Emory Vaccine Center and Emory University School of Medicine. The first author of the paper is graduate student David Holthausen, and the research grew out of collaboration with M.R. Pillai, PhD and Sanil George, PhD from the Rajiv Gandhi Center for Biotechnology. Jacob and his colleagues named one of the antiviral peptides they identified urumin, after a whip-like sword called "urumi" used in southern India centuries ago. Urumin was found in skin secretions from the Indian frog Hydrophylax bahuvistara, which were collected after mild electrical stimulation. Peptides are short chains of amino acids, the building blocks of proteins. Some anti-bacterial peptides work by punching holes in cell membranes, and are thus toxic to mammalian cells, but urumin was not. Instead, urumin appears to only disrupt the integrity of flu virus, as seen through electron microscopy. It binds the stalk of hemagglutinin, a less variable region of the flu virus that is also the target of proposed universal vaccines. This specificity could be valuable because current anti-influenza drugs target other parts of the virus, Jacob says. Because flu viruses from humans cannot infect frogs, producing urumin probably confers on frogs an advantage in fighting some other pathogen, he says. Delivered intranasally, urumin protected unvaccinated mice against a lethal dose of some flu viruses. Urumin was specific for H1 strains of flu, such as the 2009 pandemic strain, and was not effective against other current strains such as H3N2. Developing antimicrobial peptides into effective drugs has been a challenge in the past, partly because enzymes in the body can break them down. Jacob's lab is now exploring ways to stabilize antiviral peptides such as urumin, as well as looking for frog-derived peptides that are active against other viruses like dengue and Zika.


News Article | April 18, 2017
Site: www.chromatographytechniques.com

Frog mucus is loaded with molecules that kill bacteria and viruses, and researchers are beginning to investigate it as a potential source for new anti-microbial drugs. One of these "host defense peptides," courtesy of a colorful tennis-ball-sized frog species (Hydrophylax bahuvistara) from southern India, can destroy many strains of human flu and protect mice against flu infection, researchers report April 18 in the journal Immunity. This peptide is far from becoming an anti-flu drug, but this is the first evidence of its flu-killing ability. It seems to work by binding to a protein that is identical across many influenza strains, and in lab experiments, it was able to neutralize dozens of flu strains, from the 1934 archival viruses up to modern ones. The researchers named the newly identified peptide "urumin," after the urumi, a sword with a flexible blade that snaps and bends like a whip, which comes from the same Indian province, Kerala, as the frog. "Different frogs make different peptides, depending on where their habitat is. You and I make host defense peptides ourselves," said flu specialist and study co-author Joshy Jacob of Emory University. "It's a natural innate immune mediator that all living organisms maintain. We just happened to find one that the frog makes that just happens to be effective against the H1 influenza type." Practically all animals make at least a few anti-microbial host defense peptides as part of their innate immune systems, and researchers are only beginning to catalog them. However, frogs have drawn the most attention as a source of host defense peptides, because it's relatively easy to isolate the peptides from their mucus. Researchers can simply give the frogs a small electric shock or rub a powder on the frogs to make them secrete their defense peptides, which can then be collected. Researchers from the Rajiv Gandhi Center for Biotechnology in Kerala, India, have been isolating peptides from their local frogs and screening them for potential anti-bacterials, but Jacob wondered if there might also be peptides that neutralize human-infecting viruses. Jacob and his colleagues screened 32 frog defense peptides against an influenza strain and found that 4 of them had flu-busting abilities. "I was almost knocked off my chair," said Jacob. "In the beginning, I thought that when you do drug discovery, you have to go through thousands of drug candidates, even a million, before you get 1 or 2 hits. And here we did 32 peptides, and we had 4 hits." Unfortunately, when the researchers exposed isolated human red blood cells (in a dish) to the flu-buster peptides, three out of the four proved toxic. However, the fourth—urumin—seemed harmless to human cells but lethal to a wide range of flu viruses. Electron microscope images of the virus after exposure to urumin reveal a virus that has been completely dismantled. Jacob's team is still working out the details of the flu-destroying mechanism, but the urumin appears to work by targeting a viral surface protein called hemagluttinin, the H in H1N1. "The virus needs this hemagglutinin to get inside our cells," said Jacob. "What this peptide does is it binds to the hemagglutinin and destabilizes the virus. And then it kills the virus."


News Article | April 20, 2017
Site: www.futurity.org

A component of the skin mucus secreted by certain South Indian frogs can kill the H1 variety of influenza viruses, say researchers. Frogs’ skins are known to secrete peptides that defend them against bacteria. The findings of a new study suggest that the peptides represent a resource for antiviral drug discovery, too. Anti-flu peptides could come in handy when vaccines are unavailable—in the case of a new pandemic strain, or when circulating strains become resistant to current drugs, says senior author Joshy Jacob, associate professor of microbiology and immunology at Emory Vaccine Center and Emory University School of Medicine. Scientists named one of the antiviral peptides they identified urumin, after a whip-like sword called “urumi” used in southern India centuries ago. Urumin was found in skin secretions from the Indian frog Hydrophylax bahuvistara, which were collected after mild electrical stimulation. Peptides are short chains of amino acids, the building blocks of proteins. Some antibacterial peptides work by punching holes in cell membranes, and are thus toxic to mammalian cells. Some antiviral peptides from the frogs were toxic in this way, but urumin wasn’t. Instead, it appears to only disrupt the integrity of flu virus, as seen through electron microscopy. “I was almost knocked off my chair,” Jacob says. “In the beginning, I thought that when you do drug discovery, you have to go through thousands of drug candidates, even a million, before you get 1 or 2 hits. And here we did 32 peptides, and we had 4 hits.” It turns out that urumin binds the stalk of hemagglutinin, a less variable region of the flu virus that is also the target of proposed universal vaccines. This specificity could be valuable because current anti-influenza drugs target other parts of the virus, Jacob says. Because flu viruses from humans cannot infect frogs, producing urumin probably confers on frogs an advantage in fighting some other pathogen, Jacob says. Delivered intranasally, urumin protected unvaccinated mice against a lethal dose of some flu viruses. Urumin was specific for H1 strains of flu, such as the 2009 pandemic strain, and was not effective against other current strains such as H3N2. Developing antimicrobial peptides into effective drugs has been a challenge in the past, partly because enzymes in the body can break them down. Jacob’s lab is now exploring ways to stabilize antiviral peptides such as urumin, as well as looking for frog-derived peptides that are active against other viruses like dengue and Zika. The paper appears in the journal Immunity. The first author is graduate student David Holthausen, and the research grew out of a collaboration with M.R. Pillai and Sanil George of the Rajiv Gandhi Center for Biotechnology. Emory University and the Office of Research Infrastructure Programs funded the work.


News Article | April 18, 2017
Site: www.eurekalert.org

A component of the skin mucus secreted by South Indian frogs can kill the H1 variety of influenza viruses, researchers from Emory Vaccine Center and the Rajiv Gandhi Center for Biotechnology in India have discovered. Frogs' skins were known to secrete "host defense peptides" that defend them against bacteria. The finding, scheduled for publication in Immunity, suggests that the peptides represent a resource for antiviral drug discovery as well. Anti-flu peptides could become handy when vaccines are unavailable, in the case of a new pandemic strain, or when circulating strains become resistant to current drugs, says senior author Joshy Jacob, PhD, associate professor of microbiology and immunology at Emory Vaccine Center and Emory University School of Medicine. The first author of the paper is graduate student David Holthausen, and the research grew out of collaboration with M.R. Pillai, PhD and Sanil George, PhD from the Rajiv Gandhi Center for Biotechnology. Jacob and his colleagues named one of the antiviral peptides they identified urumin, after a whip-like sword called "urumi" used in southern India centuries ago. Urumin was found in skin secretions from the Indian frog Hydrophylax bahuvistara, which were collected after mild electrical stimulation. Peptides are short chains of amino acids, the building blocks of proteins. Some anti-bacterial peptides work by punching holes in cell membranes, and are thus toxic to mammalian cells, but urumin was not. Instead, urumin appears to only disrupt the integrity of flu virus, as seen through electron microscopy. It binds the stalk of hemagglutinin, a less variable region of the flu virus that is also the target of proposed universal vaccines. This specificity could be valuable because current anti-influenza drugs target other parts of the virus, Jacob says. Because flu viruses from humans cannot infect frogs, producing urumin probably confers on frogs an advantage in fighting some other pathogen, he says. Delivered intranasally, urumin protected unvaccinated mice against a lethal dose of some flu viruses. Urumin was specific for H1 strains of flu, such as the 2009 pandemic strain, and was not effective against other current strains such as H3N2. Developing antimicrobial peptides into effective drugs has been a challenge in the past, partly because enzymes in the body can break them down. Jacob's lab is now exploring ways to stabilize antiviral peptides such as urumin, as well as looking for frog-derived peptides that are active against other viruses like dengue and Zika. Holthausen is in the Immunology and Molecular Pathogenesis graduate program. Jacob's lab is based at Yerkes National Primate Research Center. The research was supported by Emory University and by the Office of Research Infrastructure Programs (Primate centers: P51OD11132).


News Article | April 18, 2017
Site: www.eurekalert.org

Frog mucus is loaded with molecules that kill bacteria and viruses, and researchers are beginning to investigate it as a potential source for new anti-microbial drugs. One of these "host defense peptides," courtesy of a colorful tennis-ball-sized frog species (Hydrophylax bahuvistara) from southern India, can destroy many strains of human flu and protect mice against flu infection, researchers report April 18 in the journal Immunity. This peptide is far from becoming an anti-flu drug, but this is the first evidence of its flu-killing ability. It seems to work by binding to a protein that is identical across many influenza strains, and in lab experiments, it was able to neutralize dozens of flu strains, from the 1934 archival viruses up to modern ones. The researchers named the newly identified peptide "urumin," after the urumi, a sword with a flexible blade that snaps and bends like a whip, which comes from the same Indian province, Kerala, as the frog. "Different frogs make different peptides, depending on where their habitat is. You and I make host defense peptides ourselves," says flu specialist and study co-author Joshy Jacob of Emory University. "It's a natural innate immune mediator that all living organisms maintain. We just happened to find one that the frog makes that just happens to be effective against the H1 influenza type." Practically all animals make at least a few anti-microbial host defense peptides as part of their innate immune systems, and researchers are only beginning to catalog them. However, frogs have drawn the most attention as a source of host defense peptides, because it's relatively easy to isolate the peptides from their mucus. Researchers can simply give the frogs a small electric shock or rub a powder on the frogs to make them secrete their defense peptides, which can then be collected. Researchers from the Rajiv Gandhi Center for Biotechnology in Kerala, India, have been isolating peptides from their local frogs and screening them for potential anti-bacterials, but Jacob wondered if there might also be peptides that neutralize human-infecting viruses. Jacob and his colleagues screened 32 frog defense peptides against an influenza strain and found that 4 of them had flu-busting abilities. "I was almost knocked off my chair," says Jacob. "In the beginning, I thought that when you do drug discovery, you have to go through thousands of drug candidates, even a million, before you get 1 or 2 hits. And here we did 32 peptides, and we had 4 hits." Unfortunately, when the researchers exposed isolated human red blood cells (in a dish) to the flu-buster peptides, three out of the four proved toxic. However, the fourth--urumin--seemed harmless to human cells but lethal to a wide range of flu viruses. Electron microscope images of the virus after exposure to urumin reveal a virus that has been completely dismantled. Jacob's team is still working out the details of the flu-destroying mechanism, but the urumin appears to work by targeting a viral surface protein called hemagluttinin, the H in H1N1. "The virus needs this hemagglutinin to get inside our cells," says Jacob. "What this peptide does is it binds to the hemagglutinin and destabilizes the virus. And then it kills the virus." This work was supported in part by a NIH base grant to Yerkes National Primate Center. Immunity, Holthausen et al.: "An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Virusest" http://www.cell.com/immunity/fulltext/S1074-7613(17)30128-0 Immunity (@ImmunityCP), published by Cell Press, is a monthly journal that reports the most important advances in immunology research. Topics include: immune cell development and senescence, signal transduction, gene regulation, innate and adaptive immunity, autoimmunity, infectious disease, allergy and asthma, transplantation, and tumor immunology. Visit: http://www. . To receive Cell Press media alerts, contact press@cell.com.


Patent
Rajiv Gandhi Center For Biotechnology | Date: 2016-05-05

This invention relates to a simple end point assay for detection of transient intracellular Ca^(2+) with broad applicability to many Ca^(2+) channel proteins comprising, Generation of expression constructs for the fusion proteins having the Ca^(2+)/calmodulin dependent protein kinase II (CaMKII) phosphorylation sites of NR2A or NR2B subunits of N-methyl-D-aspartate receptor (NMDAR) or the voltage gated potassium channel of Drosophila (Eag) or any protein sequence which binds to the T-site of CaMKII similar to NR2B, conjugated to mitochondrial localizing signal sequence, or mutants of these sequences as described herein. Generation of mammalian expression constructs of -CaMK11 as a chimera with green fluorescent protein (GFP--CaMKII) or its mutants as described herein. Site-Directed mutagenesis, Transfection, Ca^(2+) stimulation, imaging and quantification of the number of cells with Ca^(2+)-dependent signal, wherein, NMDA receptor activity assay, TRPVI receptor activity assay, GluR4 receptor activity assay are performed to detect the activity of Ca^(2+) channel proteins.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.1-3 | Award Amount: 4.19M | Year: 2011

Human papillomavirus (HPV) is responsible for approximately 25% of head and neck cancer (HNC) worldwide and appears to be associated with a better response to treatment and improved prognosis. Evidence suggests that HPV-induced HNC has steadily increased in the USA and some European countries in the last decades. However, whether this is a worldwide phenomenon and specific risk factors are associated with it remains to be proven. In addition, little is known on the natural history and risk factors of oral HPV infection. HPV-AHEAD network aims to address these and other unanswered questions on HNC etiology and epidemiology with a focus on the role of HPV. We will assemble and analyze a large collection of plasma/sera and HNC tissues from 42 centres in 16 European countries as well as HNC tissues from 7 Indian centres together with epidemiological and clinical data. HPV status in human specimens will be evaluated by different assays in central laboratories. Epidemiological studies will be conducted to establish the overall proportion and type distribution of HPV-positive HNC at different anatomical sites in European and Indian regions as well as the time trend of the proportion of HPV-positive HNC in recent decades. Using the follow-up information on HNC patients, we will further investigate whether HPV positivity confers a better prognosis and survival. We will also conduct a study in HPV-vaccinated and non-vaccinated women in order to determine risk factors and natural history of oral HPV infections. In addition, we will search for new surrogate markers for oral HPV infection to facilitate novel screening strategies. Finally, the HPV-AHEAD consortium aims to transfer technology to Indian centres as well as to develop several strategies for the training of European and Indian researchers in infections and cancers. This study will provide important insights for the screening, diagnosis, treatment and prophylaxis of HPV-associated HNC in Europe, India and elsewhere.


Nair K L.,Rajiv Gandhi Center for Biotechnology
International journal of nanomedicine | Year: 2011

Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release formulation to multiplex the therapeutic effect of cancer chemotherapy.

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