Sirtuin proteins have been shown to promote longevity in many organisms, and increased expression of one sirtuin protein, SIRT3, has been linked to increased human lifespan. New data, generated in mice, by Mahesh Gupta and colleagues, at the University of Chicago, Chicago, has revealed that Sirt3 helps protect the mouse heart.
In the study, the heart of mice lacking Sirt3 was found to show signs of becoming enlarged (a process known as cardiac hypertrophy), at about 8 weeks of age. Further, these mice responded dramatically to conditions that induce cardiac hypertrophy, whereas mice overexpressing Sirt3 were protected from cardiac hypertrophy under the same conditions. Additional analysis revealed the mechanism by which Sirt3 blocks the cardiac hypertrophic response, thereby providing protection to the mouse heart. Specifically, it acts in heart muscle cells via the protein Foxo3a to increase expression of anti-oxidant proteins, thereby reducing levels of damaging oxidants.
TITLE: Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice
AUTHOR:
Mahesh P. Gupta
University of Chicago, Chicago, Illinois, USA.
PDF of this article
Source:
Karen Honey
Journal of Clinical Investigation
понедельник, 20 июня 2011 г.
воскресенье, 19 июня 2011 г.
Pathogenic Attacks On Host Plants Have Medicinal Research Implications
Two Kansas State University researchers focusing on rice genetics are providing a better understanding of how pathogens take over a plant's nutrients.
Their research provides insight into ways of reducing crop losses or developing new avenues for medicinal research.
Frank White, professor of plant pathology, and Ginny Antony, postdoctoral fellow in plant pathology, are co-authors, in partnership with researchers at three other institutions, of an article in a recent issue of the journal Nature. The article, "Sugar transporters for intercellular exchange and nutrition of pathogens," was led by Li-Qing Chen from the department of plant biology in the Carnegie Institution for Science at Stanford University.
The project involves the identification a family of sugar transporters, called SWEETS, which transport glucose between plant cells. These transporters are also important because they are targeted by pathogens trying to obtain plant sugar for nutrition.
"It's remarkable," White said. "These bacteria are able to regulate the plant genes directly by inserting proteins into the plant cells. The proteins take over the transcription of the SWEET gene, and the plant, as a consequence, becomes susceptible to bacterial disease."
White and Antony focused specifically on rice bacterial disease and tried to understand what makes rice susceptible and what makes it resistant to specific pathogens. The K-State researchers discovered three resistance genes in rice that can be mutated in order to build the resistance of the rice against a pathogen. One of these resistance genes -- Xa13 -- is included in the Nature article and was discovered by White's lab in 2006.
"We've identified the genes that bacteria can induce to cause the plant to be susceptible," White said. "We've identified them as critical for disease from a pathogen standpoint. For the plant, these genes are involved in normal development. However, once the pathogen takes control of expression, it makes the plant susceptible."
White and Antony also have an article appearing in the December issue of the journal The Plant Cell. They collaborated with researchers from Iowa State University to investigate a second susceptibility gene and its role in the spread of disease.
White's laboratory has been working on such rice research for 15 years, but started collaborating with the Stanford researchers earlier this year.
"We have been trying to understand what the pathogen wants from the host, how the pathogen gets it, and how the host tries to defend itself," Antony said.
Although the research is important in the field of plant genetics, it has broader applications as well. Because researchers have a better understanding of how to control pathogen food supplies, they can use this research to reduce crop diseases and subsequent losses. The plant research may also apply the findings to humans or animals because both use similar sugar transporter genes to transfer glucose, leading to new possibilities for medicine and diabetes research.
Notes:
White and Antony are in the midst of a three-year, $3-million National Science Foundation grant, and have also been funded in their research by the U.S. Department of Agriculture's National Research Initiative program through the Cooperative State Research, Education and Extension Service.
Source:
Frank White
Kansas State University
Their research provides insight into ways of reducing crop losses or developing new avenues for medicinal research.
Frank White, professor of plant pathology, and Ginny Antony, postdoctoral fellow in plant pathology, are co-authors, in partnership with researchers at three other institutions, of an article in a recent issue of the journal Nature. The article, "Sugar transporters for intercellular exchange and nutrition of pathogens," was led by Li-Qing Chen from the department of plant biology in the Carnegie Institution for Science at Stanford University.
The project involves the identification a family of sugar transporters, called SWEETS, which transport glucose between plant cells. These transporters are also important because they are targeted by pathogens trying to obtain plant sugar for nutrition.
"It's remarkable," White said. "These bacteria are able to regulate the plant genes directly by inserting proteins into the plant cells. The proteins take over the transcription of the SWEET gene, and the plant, as a consequence, becomes susceptible to bacterial disease."
White and Antony focused specifically on rice bacterial disease and tried to understand what makes rice susceptible and what makes it resistant to specific pathogens. The K-State researchers discovered three resistance genes in rice that can be mutated in order to build the resistance of the rice against a pathogen. One of these resistance genes -- Xa13 -- is included in the Nature article and was discovered by White's lab in 2006.
"We've identified the genes that bacteria can induce to cause the plant to be susceptible," White said. "We've identified them as critical for disease from a pathogen standpoint. For the plant, these genes are involved in normal development. However, once the pathogen takes control of expression, it makes the plant susceptible."
White and Antony also have an article appearing in the December issue of the journal The Plant Cell. They collaborated with researchers from Iowa State University to investigate a second susceptibility gene and its role in the spread of disease.
White's laboratory has been working on such rice research for 15 years, but started collaborating with the Stanford researchers earlier this year.
"We have been trying to understand what the pathogen wants from the host, how the pathogen gets it, and how the host tries to defend itself," Antony said.
Although the research is important in the field of plant genetics, it has broader applications as well. Because researchers have a better understanding of how to control pathogen food supplies, they can use this research to reduce crop diseases and subsequent losses. The plant research may also apply the findings to humans or animals because both use similar sugar transporter genes to transfer glucose, leading to new possibilities for medicine and diabetes research.
Notes:
White and Antony are in the midst of a three-year, $3-million National Science Foundation grant, and have also been funded in their research by the U.S. Department of Agriculture's National Research Initiative program through the Cooperative State Research, Education and Extension Service.
Source:
Frank White
Kansas State University
суббота, 18 июня 2011 г.
Molecular Prosthesis Against Gout
Researchers from the ETH Zurich's Department of Biosystems Science and Engineering (D-BSSE) have devised a new method for preventing and permanently eradicating the cause of gout. It involves implanting a biological network that regulates the uric acid levels autonomously.
As Paracelsus once stated, the dose makes the poison. This not only goes for chemical substances introduced to the body, but also those produced by it. The uric acid in the blood especially needs to be in the proper dosage. If the level is too high (i.e. above 6.8 mg/dl blood), the uric acid crystallizes out, which can cause kidney stones and gout. However, uric acid is an important part of the human detoxification system, acting as a so-called "scavenger" of free radicals, which cause neurological disorders, brain diseases and tumors. A team of re-searchers headed by Professor Martin Fussenegger from ETH Zurich's D-BSSE in Basle has now succeeded in building a network of genes which permanently keep the uric acid concentration in check. The preliminary trials in mice have been encouraging. The research results will be published on Sunday in the journal Nature Biotechnology.
Self-regulating network
In most mammals, the enzyme urate oxydase controls the uric acid level. As humans evolved from the apes, however, they lost this enzyme, which is why we suffer more from an elevated uric acid concentration. Researchers from ETH Zurich set about finding a way to rectify the defect and restore the subtle control of the uric acid level. With this in mind, they put together a biological network of genes called UREX. The individual components of UREX were "programmed" differently by the researchers: a uric acid sensor constantly gauges and controls the concentration in the blood. If the uric acid level reaches an alarming concen-tration, the sensor relays the information to a genetic circuit. This then makes sure that the third component of the network releases the correct amount of urate oxydase into the blood and that the uric acid level is restored to a healthy balance. The three components of the network thus communicate with each other and work independently and automatically without any external assistance. The uric acid level can therefore be controlled permanently using UREX.
Genes left untouched
The gene network is integrated in a single cell. Around two million of these cells are enclosed in a seaweed gelatine capsule measuring 0.2 mm in diameter to protect the cells against an immune response. Pores in the capsule ensure that the cell receives an optimal supply of nutrients, the uric acid level can be gauged by the sensor and the enzyme can find its way into the blood. However, the organism does not come into contact with the network's modified genes. Even if the method were used in humans, a direct intervention in the patient's genetic make-up would not be necessary. "In the case of diseases resulting from genetic defects, it might make sense to channel genetically modified material directly into the human cells. However, this also raises concerns as the material can no longer be removed", explains Martin Fussenegger. But this is not the case with the new method: the implant can be removed safely at any time and without any after-effects.
For the ETH-Zurich professor, the result is a prime example of what the relatively new research branch of synthetic biology can achieve: "Many medical problems are solved by introducing chemical substances, i.e. medication, into the body from outside. In our method, we repair a defective metabolic pathway and help the body to treat itself in the best possible way." Martin Fussenegger refers to it fondly as a "molecular prosthesis" an artificial aid that compensates for the evolutionary lack of urate oxydase.
Gout: a scourge of mankind
Around 1 % of the population in the industrialized countries suffers from the ex-tremely painful joint disease gout due to elevated uric acid levels. There are many causes for the increase in the uric acid level: a genetic predisposition, environmental influences or an unbalanced diet. Moreover, it can lead to so-called tumor lysis syndrome after chemotherapy. Due to the intervention, tumor cells disintegrate so quickly that too much uric acid finds its way into the blood. This results in metabolic complications and possibly renal failure.
The team of researchers from ETH Zurich has successfully tested the UREX network on mice: as expected, the uric acid concentration in the blood decreased to a stable and healthy level, and the uric acid crystals in the animals' kidneys dissolved. The researchers have already filed a patent application for the network, but the next steps for its medical application are now in the hands of other partners. "We're confident that our network will complete all the necessary series of tests in the not too distant future, but in our experience it takes longer than you might hope for a finished product to reach the market", cautions Fussenegger. Once this one does, however, gout and kidney stones will be a thing of the past.
Source: ETH ZГјrich
As Paracelsus once stated, the dose makes the poison. This not only goes for chemical substances introduced to the body, but also those produced by it. The uric acid in the blood especially needs to be in the proper dosage. If the level is too high (i.e. above 6.8 mg/dl blood), the uric acid crystallizes out, which can cause kidney stones and gout. However, uric acid is an important part of the human detoxification system, acting as a so-called "scavenger" of free radicals, which cause neurological disorders, brain diseases and tumors. A team of re-searchers headed by Professor Martin Fussenegger from ETH Zurich's D-BSSE in Basle has now succeeded in building a network of genes which permanently keep the uric acid concentration in check. The preliminary trials in mice have been encouraging. The research results will be published on Sunday in the journal Nature Biotechnology.
Self-regulating network
In most mammals, the enzyme urate oxydase controls the uric acid level. As humans evolved from the apes, however, they lost this enzyme, which is why we suffer more from an elevated uric acid concentration. Researchers from ETH Zurich set about finding a way to rectify the defect and restore the subtle control of the uric acid level. With this in mind, they put together a biological network of genes called UREX. The individual components of UREX were "programmed" differently by the researchers: a uric acid sensor constantly gauges and controls the concentration in the blood. If the uric acid level reaches an alarming concen-tration, the sensor relays the information to a genetic circuit. This then makes sure that the third component of the network releases the correct amount of urate oxydase into the blood and that the uric acid level is restored to a healthy balance. The three components of the network thus communicate with each other and work independently and automatically without any external assistance. The uric acid level can therefore be controlled permanently using UREX.
Genes left untouched
The gene network is integrated in a single cell. Around two million of these cells are enclosed in a seaweed gelatine capsule measuring 0.2 mm in diameter to protect the cells against an immune response. Pores in the capsule ensure that the cell receives an optimal supply of nutrients, the uric acid level can be gauged by the sensor and the enzyme can find its way into the blood. However, the organism does not come into contact with the network's modified genes. Even if the method were used in humans, a direct intervention in the patient's genetic make-up would not be necessary. "In the case of diseases resulting from genetic defects, it might make sense to channel genetically modified material directly into the human cells. However, this also raises concerns as the material can no longer be removed", explains Martin Fussenegger. But this is not the case with the new method: the implant can be removed safely at any time and without any after-effects.
For the ETH-Zurich professor, the result is a prime example of what the relatively new research branch of synthetic biology can achieve: "Many medical problems are solved by introducing chemical substances, i.e. medication, into the body from outside. In our method, we repair a defective metabolic pathway and help the body to treat itself in the best possible way." Martin Fussenegger refers to it fondly as a "molecular prosthesis" an artificial aid that compensates for the evolutionary lack of urate oxydase.
Gout: a scourge of mankind
Around 1 % of the population in the industrialized countries suffers from the ex-tremely painful joint disease gout due to elevated uric acid levels. There are many causes for the increase in the uric acid level: a genetic predisposition, environmental influences or an unbalanced diet. Moreover, it can lead to so-called tumor lysis syndrome after chemotherapy. Due to the intervention, tumor cells disintegrate so quickly that too much uric acid finds its way into the blood. This results in metabolic complications and possibly renal failure.
The team of researchers from ETH Zurich has successfully tested the UREX network on mice: as expected, the uric acid concentration in the blood decreased to a stable and healthy level, and the uric acid crystals in the animals' kidneys dissolved. The researchers have already filed a patent application for the network, but the next steps for its medical application are now in the hands of other partners. "We're confident that our network will complete all the necessary series of tests in the not too distant future, but in our experience it takes longer than you might hope for a finished product to reach the market", cautions Fussenegger. Once this one does, however, gout and kidney stones will be a thing of the past.
Source: ETH ZГјrich
пятница, 17 июня 2011 г.
Collapse Of The Cellular Protein Network Causes Alzheimer's?
Protein aggregation underlies several neurodegenerative diseases such as Alzheimer's, Huntington's chorea or Parkinson's. Scientists at the Max Planck Institute of Biochemistry (MPIB) in Martinsried near Munich, Germany, now discovered a fundamental mechanism which explains how toxic protein aggregation occurs and why it leads to a widespread impairment of essential cellular functions. "Not all proteins are affected by aggregation", says Heidi Olzscha, PhD student at the MPIB. "Especially those proteins are susceptible, which possess specific structural characteristics and are involved in important biological processes."
To fulfill their different functions, proteins have to acquire the correct three-dimensional structure. In other words, polypeptides have to fold first. Molecular chaperones, a diverse group of conserved proteins, have specialized to assist other proteins during their folding. If the chaperones fail, misfolding and aggregation of the newly synthesized and pre-existing proteins might occur. In the worst case, this results then in neurodegenerative diseases, such as Alzheimer's, Huntington's chorea or Parkinson's. Alzheimer's disease, for example, develops because the A-beta and tau proteins aggregate, which leads to neuronal dysfunction and cell death. According to Alzheimer Forschung Initiative e. V., approximately 1.2 million people suffer from this disease only in Germany. The risk to fall ill grows with increasing age.
Scientists in the Department of Cellular Biochemistry at the Max Planck Institute of Biochemistry, headed by F.-Ulrich Hartl, now established a novel experimental model aimed at elucidating cellular protein misfolding and discovered why the misfolding and aggregation are deleterious for cells. They prepared several artificial aggregating proteins without any biological function and introduced them into cells. These model proteins clumped together, coaggregating many natural proteins and, in that way, disturbing their function. By means of quantitative proteomics, the researchers discovered that the affected proteins share certain structural characteristics which predispose them for the co-aggregation: They are large in size, less hydrophobic and show a significant increase of disorder in their structure.
"These are proteins that have not only many, but also very important functions in the cell", explains Martin Vabulas. "For instance, they are responsible for the stability of the cytoskeleton, the organization of the chromatin in nucleus, the transcription of DNA to RNA or the synthesis of proteins. Simultaneous disturbance of several of these essential processes is most probably the reason of the cellular break-down. As a consequence, protein misfolding diseases develop."
Molecular chaperones could possibly prevent this dire scenario. They are able to shield the aggregates, so that the aggregates cannot get in touch with other proteins anymore. The scientists hope that their new insights might help to develop novel therapeutic strategies in the battle against neurodegenerative diseases, especially at the earlier stages, before the irreversible collapse of cellular protein network sets in.
Sources: Max Planck Institute of Biochemistry, AlphaGalileo Foundation.
To fulfill their different functions, proteins have to acquire the correct three-dimensional structure. In other words, polypeptides have to fold first. Molecular chaperones, a diverse group of conserved proteins, have specialized to assist other proteins during their folding. If the chaperones fail, misfolding and aggregation of the newly synthesized and pre-existing proteins might occur. In the worst case, this results then in neurodegenerative diseases, such as Alzheimer's, Huntington's chorea or Parkinson's. Alzheimer's disease, for example, develops because the A-beta and tau proteins aggregate, which leads to neuronal dysfunction and cell death. According to Alzheimer Forschung Initiative e. V., approximately 1.2 million people suffer from this disease only in Germany. The risk to fall ill grows with increasing age.
Scientists in the Department of Cellular Biochemistry at the Max Planck Institute of Biochemistry, headed by F.-Ulrich Hartl, now established a novel experimental model aimed at elucidating cellular protein misfolding and discovered why the misfolding and aggregation are deleterious for cells. They prepared several artificial aggregating proteins without any biological function and introduced them into cells. These model proteins clumped together, coaggregating many natural proteins and, in that way, disturbing their function. By means of quantitative proteomics, the researchers discovered that the affected proteins share certain structural characteristics which predispose them for the co-aggregation: They are large in size, less hydrophobic and show a significant increase of disorder in their structure.
"These are proteins that have not only many, but also very important functions in the cell", explains Martin Vabulas. "For instance, they are responsible for the stability of the cytoskeleton, the organization of the chromatin in nucleus, the transcription of DNA to RNA or the synthesis of proteins. Simultaneous disturbance of several of these essential processes is most probably the reason of the cellular break-down. As a consequence, protein misfolding diseases develop."
Molecular chaperones could possibly prevent this dire scenario. They are able to shield the aggregates, so that the aggregates cannot get in touch with other proteins anymore. The scientists hope that their new insights might help to develop novel therapeutic strategies in the battle against neurodegenerative diseases, especially at the earlier stages, before the irreversible collapse of cellular protein network sets in.
Sources: Max Planck Institute of Biochemistry, AlphaGalileo Foundation.
четверг, 16 июня 2011 г.
Regulating Hematopoietic Stem Cell Homeostasis And Leukemogenesis
In the April 15th issue of G&D, Dr. Richard Flavell (Yale University) and colleagues identify the c-Cbl protein as a critical repressor of hematopoietic stem cell (HSC) self-renewal. In addition to establishing a key role for protein ubiquitylation in HSC development, this finding posits c-Cbl as a potential target in research into stem cell engineering as well as cell-based leukemia treatments.
Dr. Flavell describes the work as elucidating "a novel dimension in our understanding the self-renewal of Hematopoietic stem cells."
Like all stem cell populations, HSC reply upon asymmetric cell division to generate two different daughter cells: one future stem cell, and another cell that will further differentiate into a more specialized cell type. Thus, a balance is struck between the production of new cell types and the renewal of the stem cell pool. However, imbalances between HSC self-renewal and differentiation can lead to hematologic malignancies like leukemia.
Dr. Flavell's group discovered that the E3 ubiquitin ligase, c-Cbl, suppresses HSC self-renewal. The researchers generated transgenic mice deficient in c-Cbl, and demonstrated that these c-Cbl-mutant mice display an increased number of HSCs.
Lead author, Dr. Chozhavendan Rathinam, is confident that "our findings may facilitate the expansion and manipulation of hematopoietic stem cells for tissue engineering and stem cell based therapies."
Source: Heather Cosel-Pieper
Cold Spring Harbor Laboratory
Dr. Flavell describes the work as elucidating "a novel dimension in our understanding the self-renewal of Hematopoietic stem cells."
Like all stem cell populations, HSC reply upon asymmetric cell division to generate two different daughter cells: one future stem cell, and another cell that will further differentiate into a more specialized cell type. Thus, a balance is struck between the production of new cell types and the renewal of the stem cell pool. However, imbalances between HSC self-renewal and differentiation can lead to hematologic malignancies like leukemia.
Dr. Flavell's group discovered that the E3 ubiquitin ligase, c-Cbl, suppresses HSC self-renewal. The researchers generated transgenic mice deficient in c-Cbl, and demonstrated that these c-Cbl-mutant mice display an increased number of HSCs.
Lead author, Dr. Chozhavendan Rathinam, is confident that "our findings may facilitate the expansion and manipulation of hematopoietic stem cells for tissue engineering and stem cell based therapies."
Source: Heather Cosel-Pieper
Cold Spring Harbor Laboratory
среда, 15 июня 2011 г.
Novel Method Of Immunization That Completely Eliminates Malaria Parasites
Singapore scientists report that they have discovered a novel method of immunization that completely eliminates the malaria parasites in both stages of the parasite's development.
The scientists, part of the Singapore Immunology Network (SIgN), attribute the novel method's effectiveness in eliminating the malaria parasites to the fact that it targets common proteins that are found on the parasite in both stages of its sequential development, first, in the liver, and then in the blood.
The malaria research findings, which may serve as a basis for the development of a vaccine, were described in a "report card" about SIgN's first year in its state-of-the-art research facility on the Biopolis biomedical sciences campus of Singapore's Agency of Science, Technology and Research (A*STAR).
SIgN is a research consortium under A*STAR, which aims to make the program an international hub for immunology research.
"Building R&D is a strategic priority for Singapore," said A*STAR Chairman Lim Chuan Poh. "Singapore remains committed to investing in R&D even in this time of global financial crisis."
"The spotlight has increasingly turned on human immunology research over the last few years," said Paola Castagnoli, Ph.D., SIgN's Scientific Director. "There is increasing urgency to devise strategies and methods for translating what is already known in traditional immunology and develop it into something that can be used in the clinics and hospitals.
"SIgN will continue to ramp up its R&D efforts on human immunology as we believe that such an approach can potentially yield direct clinical applications with greater impact for human health," added Castagnoli, who is also Professor of Immunology and Pathology at the University of Milan-Bicocca.
Castagnoli noted that these plans are consistent with the scientific strategy set by SIgN Chairman Philippe Kourilsky, Ph.D., when he initiated the research program. He also is Professor and Chair of Molecular Immunology at the College de France.
During its first year, SIgN has made significant headway in three major areas of human immunity: infection, immuno-regulation and inflammation.
In cancer inflammation, SIgN scientists are using a skin tumour model that can better mimic the course of disease progression in human cancers and thus is more clinically relevant than other models. SIgN scientists found that skin tumours are able to escape detection because of immuno-tolerance, and in their studies to determine how to reverse immuno-tolerance, they have been investigating how some white blood cells (CD 8+ T cells) could play a role in this phenomenon by contributing to disease progression and the body's efforts to control the spread of the tumour.
A*STAR Chairman Lim Chuan Poh said, "Under the very able leadership of Professors Philippe Kourilsky and Paola Castagnoli, SIgN has indeed made significant progress.
They have attracted some very notable scientists and built extensive collaborations both within and outside Singapore. This is truly an anniversary to be celebrated.
"Our steady and sustained investments in R&D will not only differentiate us from the other R&D hubs, but make us very attractive as an R&D partner, and position us as the place to be for international scientific talent. Indeed, as we continue with our research activities, we are developing our capacity and positioning ourselves well for future growth once the global economy recovers."
For more information:
Ms Joyce Pang
Corporate Communications
Agency for Science, Technology and Research (A*STAR)
Singapore Immunology Network (SIgN): sign.a-star.sg
SIgN, officially inaugurated on 15 January 2008, is a research consortium under A*STAR's Biomedical Research Council aimed at building on the strengths of the existing immunology research groups at A*STAR, as well as expanding and strengthening the immunology research expertise in Singapore. SIgN's objectives include coordinating basic, translational and clinical research needed to establish immunology as a core capability in Singapore; establishing productive links with local initiatives within Biopolis and across Singapore; obtaining international recognition while establishing relationships with leading institutions in the world; and building up a strong platform in basic human immunology research for better translation of results into medical applications.
In its first year, SIgN also has rapidly expanded its stable of research talent as well as actively engaged industrial and clinical partners to develop and drive innovation in the area of human immunology. To date, 85 scientists have been recruited to SIgN вЂ" an increase of 42% since the program's official inauguration. Among the recent recruits are two notable immunologists whose unique expertise strengthens SIgN's human immunology knowledge base. They are:
Catharina Svanborg, M.D., Ph.D., a clinical immunologist and bacteriologist who came to SIgN from Lund University in Sweden where she was Professor of Clinical Immunology. She is furthering her research on HAMLET, a variant of a protein complex in human milk that has the ability to selectively kill tumour cells while leaving healthy cells unscathed.
Olaf Rotschzke, Ph.D., who came to SIgN from the Max-Delbrueck-Center in Berlin and who has more than 15 years of immunology research experience in studying a group of protective immune cells known as regulatory T cells (T-Regs), which are essential to the suppression of inflammation. Suppressing inflammation is important in treating autoimmune diseases, allergies and graft rejection. His research involves translating scientific results that have been successfully proven in animal models into therapies that can be used in human patients.
Over the past year, SIgN has built up a strong network for the exchange of ideas and expertise with over 40 research centres, hospitals and companies worldwide. It has also established several research collaborations with both local and international partners such as Singapore's Nanyang Technological University, Environmental Health Institute and Novartis Institute for Tropical Diseases; France's Institut National de la SantГ© et de la Recherche MГ©dicale; Humalys SAS; Italy's University of Milano-Bicocca; and Thailand's University of Mahidol.
SIgN is also actively collaborating with other A*STAR research units, leveraging on each other's strengths and capabilities to advance scientific knowledge. Examples of such collaborations include a hepatic disease research programme with the Singapore Institute for Clinical Sciences, joint grant call with the Singapore Bioimaging Consortium, setting up a transcriptional profiling database for immune cells with the Bioinformatics Institute and initiating projects on skin tissues with the Institute of Medical Biology.
Going forward, SIgN plans to collaborate with even more A*STAR research units such as the Experimental Therapeutics Centre (ETC), to which SIgN would bring validated products or targets for further development by ETC to the stage at which they can attract funding by venture capital investors or be out-licensed to industry.
Agency for Science, Technology and Research (A*STAR): a-star.sg
The Agency for Science, Technology and Research, or A*STAR, is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore.
A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering. We strongly support Singapore's key economic clusters by providing intellectual, human and industrial capital to our partners in industry and the healthcare sector. A*STAR oversees 22 research institutes, consortia and centres, and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR's research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.
Source: Cathy Yarbrough
Agency for Science, Technology and Research (A*STAR), Singapore
The scientists, part of the Singapore Immunology Network (SIgN), attribute the novel method's effectiveness in eliminating the malaria parasites to the fact that it targets common proteins that are found on the parasite in both stages of its sequential development, first, in the liver, and then in the blood.
The malaria research findings, which may serve as a basis for the development of a vaccine, were described in a "report card" about SIgN's first year in its state-of-the-art research facility on the Biopolis biomedical sciences campus of Singapore's Agency of Science, Technology and Research (A*STAR).
SIgN is a research consortium under A*STAR, which aims to make the program an international hub for immunology research.
"Building R&D is a strategic priority for Singapore," said A*STAR Chairman Lim Chuan Poh. "Singapore remains committed to investing in R&D even in this time of global financial crisis."
"The spotlight has increasingly turned on human immunology research over the last few years," said Paola Castagnoli, Ph.D., SIgN's Scientific Director. "There is increasing urgency to devise strategies and methods for translating what is already known in traditional immunology and develop it into something that can be used in the clinics and hospitals.
"SIgN will continue to ramp up its R&D efforts on human immunology as we believe that such an approach can potentially yield direct clinical applications with greater impact for human health," added Castagnoli, who is also Professor of Immunology and Pathology at the University of Milan-Bicocca.
Castagnoli noted that these plans are consistent with the scientific strategy set by SIgN Chairman Philippe Kourilsky, Ph.D., when he initiated the research program. He also is Professor and Chair of Molecular Immunology at the College de France.
During its first year, SIgN has made significant headway in three major areas of human immunity: infection, immuno-regulation and inflammation.
In cancer inflammation, SIgN scientists are using a skin tumour model that can better mimic the course of disease progression in human cancers and thus is more clinically relevant than other models. SIgN scientists found that skin tumours are able to escape detection because of immuno-tolerance, and in their studies to determine how to reverse immuno-tolerance, they have been investigating how some white blood cells (CD 8+ T cells) could play a role in this phenomenon by contributing to disease progression and the body's efforts to control the spread of the tumour.
A*STAR Chairman Lim Chuan Poh said, "Under the very able leadership of Professors Philippe Kourilsky and Paola Castagnoli, SIgN has indeed made significant progress.
They have attracted some very notable scientists and built extensive collaborations both within and outside Singapore. This is truly an anniversary to be celebrated.
"Our steady and sustained investments in R&D will not only differentiate us from the other R&D hubs, but make us very attractive as an R&D partner, and position us as the place to be for international scientific talent. Indeed, as we continue with our research activities, we are developing our capacity and positioning ourselves well for future growth once the global economy recovers."
For more information:
Ms Joyce Pang
Corporate Communications
Agency for Science, Technology and Research (A*STAR)
Singapore Immunology Network (SIgN): sign.a-star.sg
SIgN, officially inaugurated on 15 January 2008, is a research consortium under A*STAR's Biomedical Research Council aimed at building on the strengths of the existing immunology research groups at A*STAR, as well as expanding and strengthening the immunology research expertise in Singapore. SIgN's objectives include coordinating basic, translational and clinical research needed to establish immunology as a core capability in Singapore; establishing productive links with local initiatives within Biopolis and across Singapore; obtaining international recognition while establishing relationships with leading institutions in the world; and building up a strong platform in basic human immunology research for better translation of results into medical applications.
In its first year, SIgN also has rapidly expanded its stable of research talent as well as actively engaged industrial and clinical partners to develop and drive innovation in the area of human immunology. To date, 85 scientists have been recruited to SIgN вЂ" an increase of 42% since the program's official inauguration. Among the recent recruits are two notable immunologists whose unique expertise strengthens SIgN's human immunology knowledge base. They are:
Catharina Svanborg, M.D., Ph.D., a clinical immunologist and bacteriologist who came to SIgN from Lund University in Sweden where she was Professor of Clinical Immunology. She is furthering her research on HAMLET, a variant of a protein complex in human milk that has the ability to selectively kill tumour cells while leaving healthy cells unscathed.
Olaf Rotschzke, Ph.D., who came to SIgN from the Max-Delbrueck-Center in Berlin and who has more than 15 years of immunology research experience in studying a group of protective immune cells known as regulatory T cells (T-Regs), which are essential to the suppression of inflammation. Suppressing inflammation is important in treating autoimmune diseases, allergies and graft rejection. His research involves translating scientific results that have been successfully proven in animal models into therapies that can be used in human patients.
Over the past year, SIgN has built up a strong network for the exchange of ideas and expertise with over 40 research centres, hospitals and companies worldwide. It has also established several research collaborations with both local and international partners such as Singapore's Nanyang Technological University, Environmental Health Institute and Novartis Institute for Tropical Diseases; France's Institut National de la SantГ© et de la Recherche MГ©dicale; Humalys SAS; Italy's University of Milano-Bicocca; and Thailand's University of Mahidol.
SIgN is also actively collaborating with other A*STAR research units, leveraging on each other's strengths and capabilities to advance scientific knowledge. Examples of such collaborations include a hepatic disease research programme with the Singapore Institute for Clinical Sciences, joint grant call with the Singapore Bioimaging Consortium, setting up a transcriptional profiling database for immune cells with the Bioinformatics Institute and initiating projects on skin tissues with the Institute of Medical Biology.
Going forward, SIgN plans to collaborate with even more A*STAR research units such as the Experimental Therapeutics Centre (ETC), to which SIgN would bring validated products or targets for further development by ETC to the stage at which they can attract funding by venture capital investors or be out-licensed to industry.
Agency for Science, Technology and Research (A*STAR): a-star.sg
The Agency for Science, Technology and Research, or A*STAR, is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore.
A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering. We strongly support Singapore's key economic clusters by providing intellectual, human and industrial capital to our partners in industry and the healthcare sector. A*STAR oversees 22 research institutes, consortia and centres, and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR's research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.
Source: Cathy Yarbrough
Agency for Science, Technology and Research (A*STAR), Singapore
вторник, 14 июня 2011 г.
Key Mechanism For The Proliferation Of Epstein Barr Virus Discovered
Scientists of Helmholtz Zentrum MГјnchen have elucidated a crucial mechanism in the lytic cycle of Epstein-Barr virus. A team of researchers led by Professor Wolfgang Hammerschmidt identified the function of a protein which plays a critical role in the proliferation of the virus. The Epstein-Barr virus can induce cancer. The findings, published in the current issue of the renowned journal PNAS, represent a major step forward in understanding tumor development.
The Epstein-Barr virus (EBV), a virus of the herpes family, has two distinct life phases: After infecting a cell it first goes into a resting phase. Under certain circumstances the virus can become active and then induces tumor growth or promotes its synthesis in the cell. Especially in patients with weakened immune systems, EBV can cause its host cells to divide uncontrollably causing a tumor to develop.
The causes for the transition of EBV from the quiescent phase to an active mode particularly with respect to the responsible factors and to how the molecular mechanisms function have until now remained elusive. With their findings, the scientists at Helmholtz Zentrum MГјnchen have discovered how the virus terminates latency and activates its synthesis in the infected cells.
Professor Wolfgang Hammerschmidt, head of the Department of Gene Vectors at Helmholtz Zentrum MГјnchen, explained: "We have now identified the crucial function of the viral BZLF1 protein: It activates the genes of EBV, which are essential for the proliferation of virus particles." About 70 different genes are switched off during the latent phase because certain DNA segments are chemically modified: Some DNA building blocks carry methyl groups. They are a kind of stop signal for the cell apparatus, so that these genes cannot be converted into protein.
"BZLF1 can detect these methylation patterns in the DNA," said Markus Kalla, lead author of the study. With its DNA binding domain, the protein binds directly to the methylated DNA sequence. A second domain of BZLF1 is responsible for the reactivation of the gene. "Such a mechanism was not known before," Wolfgang Hammerschmidt said. Previous research assumed that the methyl groups had to be removed from the DNA building blocks before the transcription factors could bind to the regulatory DNA sequence and thus activate the gene.
The researchers' findings indicate that BZLF1 avoids this hurdle. Accordingly, BZLF1 appears to be essential for establishing and maintaining latency, but also for escaping from it.
During viral synthesis a large number of new particles are usually formed within the cell. To achieve this, viruses use large portions of the cell apparatus, in particular specific proteins and factors. After progeny synthesis the new viruses are released researchers speak of a lytic cycle. The disadvantage: the viruses thus attract the attention of the immune system, which then fights against the pathogen and destroys the cell supporting viral synthesis.
However, the Epstein-Barr virus uses another strategy. Instead of putting all of its energy into immediate synthesis of progeny in the infected cell, it goes into a resting phase following the infection and thus prevents a reaction of the immune system. The virus infects cells of the immune system - the so-called B cells - first inserting its DNA into their cell nucleus. Whereas most viruses immediately start their lytic proliferation cycle and thus use the cell apparatus to replicate the DNA and to generate important structural proteins from the genes, EBV drives transformation of merely a few genes from the cell into proteins. These so-called latent genes are important for the quiescent phase: They see to it that the DNA of the Epstein-Barr virus remains stable in the cell nucleus while the cell itself proliferates. This seemingly peaceful co-existence ends when the virus goes into the lytic phase or induces tumor growth.
These findings published in PNAS by Wolfgang Hammerschmidt and his colleagues constitute an important step for a better understanding of the role of EBV in tumor growth.
Source: Helmholtz Zentrum Muenchen
The Epstein-Barr virus (EBV), a virus of the herpes family, has two distinct life phases: After infecting a cell it first goes into a resting phase. Under certain circumstances the virus can become active and then induces tumor growth or promotes its synthesis in the cell. Especially in patients with weakened immune systems, EBV can cause its host cells to divide uncontrollably causing a tumor to develop.
The causes for the transition of EBV from the quiescent phase to an active mode particularly with respect to the responsible factors and to how the molecular mechanisms function have until now remained elusive. With their findings, the scientists at Helmholtz Zentrum MГјnchen have discovered how the virus terminates latency and activates its synthesis in the infected cells.
Professor Wolfgang Hammerschmidt, head of the Department of Gene Vectors at Helmholtz Zentrum MГјnchen, explained: "We have now identified the crucial function of the viral BZLF1 protein: It activates the genes of EBV, which are essential for the proliferation of virus particles." About 70 different genes are switched off during the latent phase because certain DNA segments are chemically modified: Some DNA building blocks carry methyl groups. They are a kind of stop signal for the cell apparatus, so that these genes cannot be converted into protein.
"BZLF1 can detect these methylation patterns in the DNA," said Markus Kalla, lead author of the study. With its DNA binding domain, the protein binds directly to the methylated DNA sequence. A second domain of BZLF1 is responsible for the reactivation of the gene. "Such a mechanism was not known before," Wolfgang Hammerschmidt said. Previous research assumed that the methyl groups had to be removed from the DNA building blocks before the transcription factors could bind to the regulatory DNA sequence and thus activate the gene.
The researchers' findings indicate that BZLF1 avoids this hurdle. Accordingly, BZLF1 appears to be essential for establishing and maintaining latency, but also for escaping from it.
During viral synthesis a large number of new particles are usually formed within the cell. To achieve this, viruses use large portions of the cell apparatus, in particular specific proteins and factors. After progeny synthesis the new viruses are released researchers speak of a lytic cycle. The disadvantage: the viruses thus attract the attention of the immune system, which then fights against the pathogen and destroys the cell supporting viral synthesis.
However, the Epstein-Barr virus uses another strategy. Instead of putting all of its energy into immediate synthesis of progeny in the infected cell, it goes into a resting phase following the infection and thus prevents a reaction of the immune system. The virus infects cells of the immune system - the so-called B cells - first inserting its DNA into their cell nucleus. Whereas most viruses immediately start their lytic proliferation cycle and thus use the cell apparatus to replicate the DNA and to generate important structural proteins from the genes, EBV drives transformation of merely a few genes from the cell into proteins. These so-called latent genes are important for the quiescent phase: They see to it that the DNA of the Epstein-Barr virus remains stable in the cell nucleus while the cell itself proliferates. This seemingly peaceful co-existence ends when the virus goes into the lytic phase or induces tumor growth.
These findings published in PNAS by Wolfgang Hammerschmidt and his colleagues constitute an important step for a better understanding of the role of EBV in tumor growth.
Source: Helmholtz Zentrum Muenchen
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