Site of the day: no site
The Bureau of Piracy is no more
The controvertial group that founded the filesharing website Pirate Bay has disbanded.
Based in Sweden, Piratbyran (or ‘piracy bureau’ in English) was opposed to copyright and promoted file sharing, much to the chagrin of the entertainment industry. The site provided an index of films, games, music and TV programmes, directing users to BitTorrent files where they could be illegaly downloaded.
Since the site went live in 2003, its founders have been raided by the police and charged with copyright infringement, with a variety of lawsuits being brought against them.
One of these founders, Marcin de Kaminski, told BBC News that the group no longer feels “needed”. He went on to comment on the sudden death of one of the other core members, Ibi Kopimi Botani:
“The discussions about abolishing Piratbyrån have been going on for years already, but this weekend a beloved friend and member died, and we decided it was time to move on for real, since the group could not be the same without him anyhow. It felt like a good time for passing this part of life”.
The move to dissolve Piratbyran was announced on a blog post, where Marcin de Kaminski encouraged file sharers to continue The Pirate Bay’s work:
“If you want to honour Ibi or The Bureau of Piracy, please make something cool out of it. We all need that”.
(http://www.geeks.co.uk/24299-pirate-bay-founders-disband)
http://www.inquisitr.com/77365/original-pirate-bay-founders-disband/
http://torrentfreak.com/pirate-bays-founding-group-piratbyran-disbands-100623/
http://dekaminski.se/2010/06/nu-finns-inte-piratbyran-mer/
Just no words.
Tuesday, June 29, 2010
LHC News
Site of the day: no site
http://news.bbc.co.uk/2/hi/science_and_environment/10430234.stm
Ohhh, what a messy month...
http://news.bbc.co.uk/2/hi/science_and_environment/10430234.stm
Ohhh, what a messy month...
Sunday, June 20, 2010
In Pursuit of the Energy of Life: Researchers Decipher Makeup of Generators in Cellular Power Plants
Site of the day: http://uberaffiliate.com/
ScienceDaily (June 21, 2010) — Scientists from the Institute of Biochemistry and Molecular Biology and Collaborative Research Center 746 of the University of Freiburg have discovered a new mechanism which plays an essential role in the assembly and growth of mitochondria, the "power plants" of the cell.
These organelles make energy stored in food ready for use by the cell. The generators in the cellular power plants are biological membranes located inside the mitochondria. Even minute errors in the composition of the inner mitochondrial membrane can lead to severe metabolic derangements, which can have an especially negative impact on the energy-hungry muscle and nerve cells.
In order to function, the cellular generators depend on the support of numerous highly specialized membrane proteins in the inner mitochondrial membrane. For the most part, these proteins are synthesized outside of the organelles and then imported with the help of protein translocases. Fundamental processes like this follow the same principles in all organisms, from unicellular life forms to human beings. The scientists were thus able to use mitochondria from baker's yeast as a model system for their study, which has now been published in the journal Current Biology.
In investigating the insertion of a family of membrane proteins which is of great pharmacological interest, the so-called ABC transporters, the research team made the surprising discovery that some segments of the transporters are evidently initially skipped by the insertion machinery and transported completely over the membrane. "These errors in membrane insertion are then repaired by another translocase which is very old from an evolutionary perspective," says Maria Bohnert, doctoral student and Boehringer-Ingelheim Scholarship recipient. Thus, the scientists were able to demonstrate for the first time that at least two different protein translocases cooperate closely to insert proteins with complex structures into the inner mitochondrial membrane.
In clarifying this coupled mechanism of membrane insertion, project head Dr. Martin van der Laan and his team have solved a hotly debated scientific problem and made a major contribution to our understanding of the composition and functioning of cellular power plants. The findings may help scientists to throw light on the mechanisms of diseases caused by defects in the biogenesis of mitochondria.
Journal Reference:
Maria Bohnert, Peter Rehling, Bernard Guiard, Johannes M. Herrmann, Nikolaus Pfanner, and Martin van der Laan. Cooperation of Stop-Transfer and Conservative Sorting Mechanisms in Mitochondrial Protein Transport. Current Biology, 2010; DOI: 10.1016/j.cub.2010.05.058
(http://www.sciencedaily.com/releases/2010/06/100618082215.htm)
ScienceDaily (June 21, 2010) — Scientists from the Institute of Biochemistry and Molecular Biology and Collaborative Research Center 746 of the University of Freiburg have discovered a new mechanism which plays an essential role in the assembly and growth of mitochondria, the "power plants" of the cell.
These organelles make energy stored in food ready for use by the cell. The generators in the cellular power plants are biological membranes located inside the mitochondria. Even minute errors in the composition of the inner mitochondrial membrane can lead to severe metabolic derangements, which can have an especially negative impact on the energy-hungry muscle and nerve cells.
In order to function, the cellular generators depend on the support of numerous highly specialized membrane proteins in the inner mitochondrial membrane. For the most part, these proteins are synthesized outside of the organelles and then imported with the help of protein translocases. Fundamental processes like this follow the same principles in all organisms, from unicellular life forms to human beings. The scientists were thus able to use mitochondria from baker's yeast as a model system for their study, which has now been published in the journal Current Biology.
In investigating the insertion of a family of membrane proteins which is of great pharmacological interest, the so-called ABC transporters, the research team made the surprising discovery that some segments of the transporters are evidently initially skipped by the insertion machinery and transported completely over the membrane. "These errors in membrane insertion are then repaired by another translocase which is very old from an evolutionary perspective," says Maria Bohnert, doctoral student and Boehringer-Ingelheim Scholarship recipient. Thus, the scientists were able to demonstrate for the first time that at least two different protein translocases cooperate closely to insert proteins with complex structures into the inner mitochondrial membrane.
In clarifying this coupled mechanism of membrane insertion, project head Dr. Martin van der Laan and his team have solved a hotly debated scientific problem and made a major contribution to our understanding of the composition and functioning of cellular power plants. The findings may help scientists to throw light on the mechanisms of diseases caused by defects in the biogenesis of mitochondria.
Journal Reference:
Maria Bohnert, Peter Rehling, Bernard Guiard, Johannes M. Herrmann, Nikolaus Pfanner, and Martin van der Laan. Cooperation of Stop-Transfer and Conservative Sorting Mechanisms in Mitochondrial Protein Transport. Current Biology, 2010; DOI: 10.1016/j.cub.2010.05.058
(http://www.sciencedaily.com/releases/2010/06/100618082215.htm)
Fuzzy Logic Predicts Cell Aging
Site of the day: http://uberaffiliate.com/
ScienceDaily (June 18, 2010) — The process of aging disturbs a broad range of cellular mechanisms in a complex fashion and is not well understood. Computer models using fuzzy logic might help to unravel these complexities and predict how aging progresses in cells and organisms, according to a study from Drexel University in Philadelphia and Children's Hospital Boston.
"One important goal of computational approaches in aging is to develop integrated models of a unifying aging theory in order to better understand the progression of aging phenotypes grounded on molecular mechanisms," said Andres Kriete, Associate Professor at Drexel's School of Biomedical Engineering, Science and Health Systems and lead author of the study.
The study, which will appear in the June issue of PLoS Computational Biology, relates progressive damage and dysfunction in aging, dubbed a vicious cycle, to inflammatory and metabolic stress response pathways. Interestingly, the activation of these pathways remodels the inner functioning of the cell in a protective and adaptive manner and thus extends lifespan.
This is the first time that scientists have applied fuzzy logic modeling to the field of aging. "Since cellular biodynamics in aging may be considered a complex control system, a fuzzy logic approach seems to be particularly suitable," said Dr. William Bosl, co-author of this study. Dr. Bosl, a staff scientist in the Informatics Program at Children's Hospital Boston, developed a fuzzy logic modeling platform called Bionet together with a cell biologist, Dr. Rong Li of the Stowers Institute for Medical Research in Kansas City, to study the complex interactions that occur in a cell's machinery using the kind of qualitative information gained from laboratory experiments.
Fuzzy logic can handle imprecise input, but makes precise decisions and has wide industrial applications from air conditioning to anti-lock break systems in cars, using predefined rules. In a similar fashion, the aging model relies on sets of rules drawn from experimental data to describe molecular interactions. "Integration of such data is the declared goal of systems biology, which enables simulation of the response of cells to signaling cues, cell cycling and cell death," said Glenn Booker, who is Faculty at the College of Information Science and Technology at Drexel and co-author on the study.
Applications in aging are currently geared towards deciphering the underlying connections and networks. "We have to realize that the real strength of computational systems biology in aging is to be able to predict and develop strategies to control cellular networks better as they may be related to age related diseases," said Dr. Kriete, "and our approach is just a first step in this direction."
Journal Reference:
Kriete A, Bosl WJ, Booker G. Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses. PLoS Computational Biology, 2010; 6 (6): e1000820 DOI: 10.1371/journal.pcbi.1000820
(http://www.sciencedaily.com/releases/2010/06/100617185127.htm)
ScienceDaily (June 18, 2010) — The process of aging disturbs a broad range of cellular mechanisms in a complex fashion and is not well understood. Computer models using fuzzy logic might help to unravel these complexities and predict how aging progresses in cells and organisms, according to a study from Drexel University in Philadelphia and Children's Hospital Boston.
"One important goal of computational approaches in aging is to develop integrated models of a unifying aging theory in order to better understand the progression of aging phenotypes grounded on molecular mechanisms," said Andres Kriete, Associate Professor at Drexel's School of Biomedical Engineering, Science and Health Systems and lead author of the study.
The study, which will appear in the June issue of PLoS Computational Biology, relates progressive damage and dysfunction in aging, dubbed a vicious cycle, to inflammatory and metabolic stress response pathways. Interestingly, the activation of these pathways remodels the inner functioning of the cell in a protective and adaptive manner and thus extends lifespan.
This is the first time that scientists have applied fuzzy logic modeling to the field of aging. "Since cellular biodynamics in aging may be considered a complex control system, a fuzzy logic approach seems to be particularly suitable," said Dr. William Bosl, co-author of this study. Dr. Bosl, a staff scientist in the Informatics Program at Children's Hospital Boston, developed a fuzzy logic modeling platform called Bionet together with a cell biologist, Dr. Rong Li of the Stowers Institute for Medical Research in Kansas City, to study the complex interactions that occur in a cell's machinery using the kind of qualitative information gained from laboratory experiments.
Fuzzy logic can handle imprecise input, but makes precise decisions and has wide industrial applications from air conditioning to anti-lock break systems in cars, using predefined rules. In a similar fashion, the aging model relies on sets of rules drawn from experimental data to describe molecular interactions. "Integration of such data is the declared goal of systems biology, which enables simulation of the response of cells to signaling cues, cell cycling and cell death," said Glenn Booker, who is Faculty at the College of Information Science and Technology at Drexel and co-author on the study.
Applications in aging are currently geared towards deciphering the underlying connections and networks. "We have to realize that the real strength of computational systems biology in aging is to be able to predict and develop strategies to control cellular networks better as they may be related to age related diseases," said Dr. Kriete, "and our approach is just a first step in this direction."
Journal Reference:
Kriete A, Bosl WJ, Booker G. Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses. PLoS Computational Biology, 2010; 6 (6): e1000820 DOI: 10.1371/journal.pcbi.1000820
(http://www.sciencedaily.com/releases/2010/06/100617185127.htm)
Protein's Role in Cell Division Uncovered
Site of the day: http://uberaffiliate.com/
ScienceDaily (June 16, 2010) — A Florida State University researcher has identified the important role that a key protein plays in cell division, and that discovery could lead to a greater understanding of stem cells.
Timothy L. Megraw, an associate professor in the College of Medicine, has outlined his findings in the cover story of the June 15 issue of Developmental Cell. The article was co-authored by researchers from the University of Texas Southwestern Medical Center at Dallas and the University of North Texas.
In August, Megraw received a four-year, $1.2 million grant from the National Institutes of Health to explore the role of centrosomes and cilia in cell division and their connections to human disease.
One long-term goal of Megraw's research has been to discover which parts of the cell play which roles in cell division. The centrosome is an important player. When a cell is ready to divide, it typically has two centrosomes, each containing a "mother and daughter" pair of centrioles tightly connected to each other, or "engaged."
"Two is important," Megraw said, "because you divide your genetic material into two equal sets. Each of these centriole pairs organizes the cytoskeletal machinery that pulls the chromosomes apart. So you don't want there to be more than two, because then you run the risk of unequal separation of the chromosomes."
The centrioles are supposed to replicate only once during the cell cycle. What keeps them from replicating more often was discovered a few years ago, Megraw said, when researchers identified mother-daughter engagement as the key. Once those two become disengaged, it acts as the "licensing" step, in effect giving the centrioles permission to replicate.
Unknown until now, Megraw said, was what regulated those centrioles to remain engaged until the proper time, to prevent excess replication. He suspected that the protein CDK5RAP2 was at least partly responsible. His team tested the protein's role using a mutant mouse in which the protein was "knocked out" and not functioning. These researchers looked for any effects on engagement and "cohesion," in which centriole pairs are tethered by fibers.
They noted in the mutant mouse that engagement and cohesion did not occur in their typical orderly fashion and that centrioles were more numerous and often single rather than paired. The amplified centrioles assembled multipolar spindles, a potential hazard for chromosomal stability. The researchers concluded that CDK5RAP2 is required to maintain centriole engagement and cohesion, thereby restricting centriole replication.
They are looking at how this discovery might apply to the human brain.
"The two mouse mutants we made mimic the two known mutations in humans in CDK5RAP2 -- which has another name, MCPH3, in humans," Megraw said. "The disease associated with that is a small brain.
"Our next step is to look at the brains of the mice and try to determine what's wrong. We think it's the stem cells -- that the progenitors that give rise to all the neurons in the brain are dying early or changing from a progenitor into a neuron too early."
Another gene called myomegalin might be functionally redundant to CDK5RAP2, Megraw said, adding, "Our goal is to knock that out, too."
The research his lab has done might also be applicable to cancer drugs for humans, he said. Centrosomes organize microtubules, which are structures in the cell that many important anti-cancer drugs target.
"The amplified centrioles and multipolar spindles suggest that the mutant mice may be more susceptible to developing cancers," Megraw said. "We are in a position to test this with our new mouse models."
Journal Reference:
Jose A. Barrera, Ling-Rong Kao, Robert E. Hammer, Joachim Seemann, Jannon L. Fuchs, Timothy L. Megraw. CDK5RAP2 Regulates Centriole Engagement and Cohesion in Mice. Developmental Cell, 2010; 18 (6): 913 DOI: 10.1016/j.devcel.2010.05.017
(http://www.sciencedaily.com/releases/2010/06/100615163156.htm)
ScienceDaily (June 16, 2010) — A Florida State University researcher has identified the important role that a key protein plays in cell division, and that discovery could lead to a greater understanding of stem cells.
Timothy L. Megraw, an associate professor in the College of Medicine, has outlined his findings in the cover story of the June 15 issue of Developmental Cell. The article was co-authored by researchers from the University of Texas Southwestern Medical Center at Dallas and the University of North Texas.
In August, Megraw received a four-year, $1.2 million grant from the National Institutes of Health to explore the role of centrosomes and cilia in cell division and their connections to human disease.
One long-term goal of Megraw's research has been to discover which parts of the cell play which roles in cell division. The centrosome is an important player. When a cell is ready to divide, it typically has two centrosomes, each containing a "mother and daughter" pair of centrioles tightly connected to each other, or "engaged."
"Two is important," Megraw said, "because you divide your genetic material into two equal sets. Each of these centriole pairs organizes the cytoskeletal machinery that pulls the chromosomes apart. So you don't want there to be more than two, because then you run the risk of unequal separation of the chromosomes."
The centrioles are supposed to replicate only once during the cell cycle. What keeps them from replicating more often was discovered a few years ago, Megraw said, when researchers identified mother-daughter engagement as the key. Once those two become disengaged, it acts as the "licensing" step, in effect giving the centrioles permission to replicate.
Unknown until now, Megraw said, was what regulated those centrioles to remain engaged until the proper time, to prevent excess replication. He suspected that the protein CDK5RAP2 was at least partly responsible. His team tested the protein's role using a mutant mouse in which the protein was "knocked out" and not functioning. These researchers looked for any effects on engagement and "cohesion," in which centriole pairs are tethered by fibers.
They noted in the mutant mouse that engagement and cohesion did not occur in their typical orderly fashion and that centrioles were more numerous and often single rather than paired. The amplified centrioles assembled multipolar spindles, a potential hazard for chromosomal stability. The researchers concluded that CDK5RAP2 is required to maintain centriole engagement and cohesion, thereby restricting centriole replication.
They are looking at how this discovery might apply to the human brain.
"The two mouse mutants we made mimic the two known mutations in humans in CDK5RAP2 -- which has another name, MCPH3, in humans," Megraw said. "The disease associated with that is a small brain.
"Our next step is to look at the brains of the mice and try to determine what's wrong. We think it's the stem cells -- that the progenitors that give rise to all the neurons in the brain are dying early or changing from a progenitor into a neuron too early."
Another gene called myomegalin might be functionally redundant to CDK5RAP2, Megraw said, adding, "Our goal is to knock that out, too."
The research his lab has done might also be applicable to cancer drugs for humans, he said. Centrosomes organize microtubules, which are structures in the cell that many important anti-cancer drugs target.
"The amplified centrioles and multipolar spindles suggest that the mutant mice may be more susceptible to developing cancers," Megraw said. "We are in a position to test this with our new mouse models."
Journal Reference:
Jose A. Barrera, Ling-Rong Kao, Robert E. Hammer, Joachim Seemann, Jannon L. Fuchs, Timothy L. Megraw. CDK5RAP2 Regulates Centriole Engagement and Cohesion in Mice. Developmental Cell, 2010; 18 (6): 913 DOI: 10.1016/j.devcel.2010.05.017
(http://www.sciencedaily.com/releases/2010/06/100615163156.htm)
Biomolecular Modeling: Scientists Discover 'Breakwater' to Help Control Electron Transfer
Site of the day: http://uberaffiliate.com/
ScienceDaily (June 16, 2010) — Researchers at the University of Calgary found that amino acid residues form a type of barrier to help in the process of electron transfer between proteins.
"This raises the bar for biomolecular modeling," says Dennis Salahub, U of C co-author of a paper published in the journal Proceedings of the National Academy of Sciences (PNAS). "At a fundamental level, it is by far the most detailed insight that has been obtained for the dynamic role of water in this kind of electron transfer, or for that matter any biochemical reaction."
Electron transfer between proteins is the cornerstone of biological energy transfer. Every life-form uses this process to convert food or sunlight into chemical energy.
The interdisciplinary team of researchers found that the electron travels over a bridge made of a water molecule, while residues on one of the proteins form a sort of 'molecular breakwater' to keep other water molecules away while the electron travels across the bridge.
"You don't want too many (water molecules around the bridge) because it gets too crowded and they're all bumping into each other and you can't get one to fit at just the right position and the right angle (for the bridge) for any length of time," says PhD student and co-author Nathan Babcock. "It's like being on a crowded subway where you can't get comfortable."
In artificial mutations with a faulty breakwater, the water bridge is disrupted and the rate of electron transfer is markedly reduced, he says.
Using the CHARMM molecular simulation computer program, the research team examined a 40 nanosecond period of electronic coupling of the proteins methylamine dehydrogenase and amicyanin from the bacterium Paracoccus denitrificans.
"This is fundamental research but you can imagine how studies like this can be applied to various genetically modified organisms, and if you can gain control over some, you can use it to either speed up or slow down a particular reaction," says Salahub.
He says the work was made possible with the collaboration of two of the U of C's interdisciplinary research institutes; the Institute for Biocomplexity and Informatics (IBI) and the Institute for Quantum Information Science (IQIS).
Babcock, whose background is in quantum information theory, was pleased to do research at the union of these two disciplines.
"When you think of quantum mechanics, usually you're thinking solid state semi conductors, atoms trapped with lasers, etc. It's usually cold laboratory stuff, not warm globby biological stuff," says the PhD student. "I think the union of biology and quantum mechanics is very, very exciting."
The study was published on June 14 in the journal Proceedings of the National Academy of Sciences by Nathan Babcock and Aurelien de la Lande, now at the CNRS in France, Jan Rezac, now at the Czech Academy of Science, Barry Sanders, iCORE Chair of Quantum Information Science at U of C and Dennis Salahub, Director of the Institute for Biocomplexity and Informatics and Professor in the Department of Chemistry.
Journal Reference:
Aurélien De La Lande, Nathan S. Babcock, Jan Řezáč, Barry C. Sanders, Dennis R. Salahub. Surface residues dynamically organize water bridges to enhance electron transfer between proteins. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.0914457107
(http://www.sciencedaily.com/releases/2010/06/100614160203.htm)
ScienceDaily (June 16, 2010) — Researchers at the University of Calgary found that amino acid residues form a type of barrier to help in the process of electron transfer between proteins.
"This raises the bar for biomolecular modeling," says Dennis Salahub, U of C co-author of a paper published in the journal Proceedings of the National Academy of Sciences (PNAS). "At a fundamental level, it is by far the most detailed insight that has been obtained for the dynamic role of water in this kind of electron transfer, or for that matter any biochemical reaction."
Electron transfer between proteins is the cornerstone of biological energy transfer. Every life-form uses this process to convert food or sunlight into chemical energy.
The interdisciplinary team of researchers found that the electron travels over a bridge made of a water molecule, while residues on one of the proteins form a sort of 'molecular breakwater' to keep other water molecules away while the electron travels across the bridge.
"You don't want too many (water molecules around the bridge) because it gets too crowded and they're all bumping into each other and you can't get one to fit at just the right position and the right angle (for the bridge) for any length of time," says PhD student and co-author Nathan Babcock. "It's like being on a crowded subway where you can't get comfortable."
In artificial mutations with a faulty breakwater, the water bridge is disrupted and the rate of electron transfer is markedly reduced, he says.
Using the CHARMM molecular simulation computer program, the research team examined a 40 nanosecond period of electronic coupling of the proteins methylamine dehydrogenase and amicyanin from the bacterium Paracoccus denitrificans.
"This is fundamental research but you can imagine how studies like this can be applied to various genetically modified organisms, and if you can gain control over some, you can use it to either speed up or slow down a particular reaction," says Salahub.
He says the work was made possible with the collaboration of two of the U of C's interdisciplinary research institutes; the Institute for Biocomplexity and Informatics (IBI) and the Institute for Quantum Information Science (IQIS).
Babcock, whose background is in quantum information theory, was pleased to do research at the union of these two disciplines.
"When you think of quantum mechanics, usually you're thinking solid state semi conductors, atoms trapped with lasers, etc. It's usually cold laboratory stuff, not warm globby biological stuff," says the PhD student. "I think the union of biology and quantum mechanics is very, very exciting."
The study was published on June 14 in the journal Proceedings of the National Academy of Sciences by Nathan Babcock and Aurelien de la Lande, now at the CNRS in France, Jan Rezac, now at the Czech Academy of Science, Barry Sanders, iCORE Chair of Quantum Information Science at U of C and Dennis Salahub, Director of the Institute for Biocomplexity and Informatics and Professor in the Department of Chemistry.
Journal Reference:
Aurélien De La Lande, Nathan S. Babcock, Jan Řezáč, Barry C. Sanders, Dennis R. Salahub. Surface residues dynamically organize water bridges to enhance electron transfer between proteins. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.0914457107
(http://www.sciencedaily.com/releases/2010/06/100614160203.htm)
Alternative Pathway to Malaria Infection Identified
Site of the day: http://uberaffiliate.com/
ScienceDaily (June 17, 2010) — Discovery of a key red cell molecule used by the malaria parasite gives renewed hope for an effective vaccine in the future, according to an international team of researchers.
Plasmodium falciparum, a blood parasite that causes malaria by invading and multiplying in the red blood cells, kills 1 to 2 million people annually.
"How the parasite invades red blood cells is not completely understood," said Jose A. Stoute, M.D., senior investigator and team leader, Department of Medicine, Division of Infectious Diseases and Epidemiology, Penn State College of Medicine. "For many years it has been known that proteins called glycophorins are used by the parasite to gain entry into the red cell."
Because infection can take place without glycophorins, researchers suspected that another protein is also involved. The identity of this protein remained a mystery for 20 years and it was named the "X" receptor. A team of researchers now reports in PLoS Pathogens, the identity of this protein as the complement receptor 1 (CR1), also known to help protect red cells from attack by the immune system. CR1 has been suspected of having other roles in the development of malaria complications. The team was able to demonstrate that this protein is important in the invasion of red cells by using several laboratory strains of malaria as well as strains obtained from Kenya.
"Our findings suggest that for many malaria strains, CR1 is an alternative receptor to glycophorins on intact red cells," Stoute said.
According to the researchers, the reasons malaria may use the CR1 protein instead of glycophorins are if the parasite encounters a variant that lacks the glycophorin receptor; if the immune system mounts a response against parasite proteins involved in the dominant pathway due to a previous infection; or if the host were to be vaccinated with a vaccine that blocks the glycophorin pathway.
"This work has important implications for the future development of a vaccine against malaria," Stoute said. "Therefore, it is imperative that all the major invasion pathways be represented in a future malaria blood stage vaccine."
Vaccines that target parasite proteins involved in the dominant glycophorin pathway, but do not block the CR1 pathway, may cause proliferation of parasites that rely on the CR1 pathway for infection.
"The demonstration that CR1 is a receptor of P. falciparum will facilitate the identification of additional parasite proteins that allow it to bind to the blood cell, and the future development of a vaccine that effectively blocks red cell invasion," said Carmenza Spadafora, lead author and scientist at the Institute for Advanced Science and High Technology Studies, Republic of Panama.
Working with Stoute and Spadafora were scientists from the Walter Reed Army Institute of Research's malaria research program, including Gordon A. Awandare and parastiologists Karen M. Kopydlowski and J. Kathleen Moch. The collaboration also included Jozsef Czege, Biomedical Instrumentation Center, Uniformed Services University of the Health Sciences; Robert W. Finberg, University of Massachusetts Medical School; and George C. Tsokos, Beth Israel Deaconess Medical Center, Harvard Medical School.
The National Institutes of Health, the Fogarty International Center, and the Department of Defense supported this work. In addition, Carmenza Spadafora received support from the National Secretariat of Science and Technology, Republic of Panama.
Journal Reference:
Carmenza Spadafora, Gordon A Awandare, Karen M Kopydlowski, Jozsef Czege, J Kathleen Moch, Robert W Finberg, George C Tsokos, José A Stoute José A Stoute. Complement Receptor 1 Is a Sialic Acid-Independent Erythrocyte Receptor of Plasmodium falciparum. PLoS Pathogens, 2010; 6 (6): e1000968 DOI: 10.1371/journal.ppat.1000968
(http://www.sciencedaily.com/releases/2010/06/100617185123.htm)
ScienceDaily (June 17, 2010) — Discovery of a key red cell molecule used by the malaria parasite gives renewed hope for an effective vaccine in the future, according to an international team of researchers.
Plasmodium falciparum, a blood parasite that causes malaria by invading and multiplying in the red blood cells, kills 1 to 2 million people annually.
"How the parasite invades red blood cells is not completely understood," said Jose A. Stoute, M.D., senior investigator and team leader, Department of Medicine, Division of Infectious Diseases and Epidemiology, Penn State College of Medicine. "For many years it has been known that proteins called glycophorins are used by the parasite to gain entry into the red cell."
Because infection can take place without glycophorins, researchers suspected that another protein is also involved. The identity of this protein remained a mystery for 20 years and it was named the "X" receptor. A team of researchers now reports in PLoS Pathogens, the identity of this protein as the complement receptor 1 (CR1), also known to help protect red cells from attack by the immune system. CR1 has been suspected of having other roles in the development of malaria complications. The team was able to demonstrate that this protein is important in the invasion of red cells by using several laboratory strains of malaria as well as strains obtained from Kenya.
"Our findings suggest that for many malaria strains, CR1 is an alternative receptor to glycophorins on intact red cells," Stoute said.
According to the researchers, the reasons malaria may use the CR1 protein instead of glycophorins are if the parasite encounters a variant that lacks the glycophorin receptor; if the immune system mounts a response against parasite proteins involved in the dominant pathway due to a previous infection; or if the host were to be vaccinated with a vaccine that blocks the glycophorin pathway.
"This work has important implications for the future development of a vaccine against malaria," Stoute said. "Therefore, it is imperative that all the major invasion pathways be represented in a future malaria blood stage vaccine."
Vaccines that target parasite proteins involved in the dominant glycophorin pathway, but do not block the CR1 pathway, may cause proliferation of parasites that rely on the CR1 pathway for infection.
"The demonstration that CR1 is a receptor of P. falciparum will facilitate the identification of additional parasite proteins that allow it to bind to the blood cell, and the future development of a vaccine that effectively blocks red cell invasion," said Carmenza Spadafora, lead author and scientist at the Institute for Advanced Science and High Technology Studies, Republic of Panama.
Working with Stoute and Spadafora were scientists from the Walter Reed Army Institute of Research's malaria research program, including Gordon A. Awandare and parastiologists Karen M. Kopydlowski and J. Kathleen Moch. The collaboration also included Jozsef Czege, Biomedical Instrumentation Center, Uniformed Services University of the Health Sciences; Robert W. Finberg, University of Massachusetts Medical School; and George C. Tsokos, Beth Israel Deaconess Medical Center, Harvard Medical School.
The National Institutes of Health, the Fogarty International Center, and the Department of Defense supported this work. In addition, Carmenza Spadafora received support from the National Secretariat of Science and Technology, Republic of Panama.
Journal Reference:
Carmenza Spadafora, Gordon A Awandare, Karen M Kopydlowski, Jozsef Czege, J Kathleen Moch, Robert W Finberg, George C Tsokos, José A Stoute José A Stoute. Complement Receptor 1 Is a Sialic Acid-Independent Erythrocyte Receptor of Plasmodium falciparum. PLoS Pathogens, 2010; 6 (6): e1000968 DOI: 10.1371/journal.ppat.1000968
(http://www.sciencedaily.com/releases/2010/06/100617185123.htm)
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