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Archive for March, 2006

‘Accelerated Evolution’ Converts RNA Enzyme To DNA Enzyme In Vitro

Posted by tumicrobiology on March 28, 2006

Scientists at The Scripps Research Institute have successfully converted an RNA enzyme (ribozyme) into a DNA enzyme (deoxyribozyme) through a process of accelerated in vitro evolution. The molecular conversion or transfer of both genetic information and catalytic function between these two different genetic systems, which are both based on nucleic acid-like molecules, is exactly what many scientists believe occurred during the very earliest period of earth's existence.

This "evolutionary conversion" provides a modern-day snapshot of how life as we understand it may have first evolved out of the earliest primordial mix of RNA-like molecules-sometimes referred to as the "pre-RNA world"-into a more complex form of RNA-based life (or the "RNA world") and eventually to cellular life based on DNA and proteins. Nucleic acids are large complex molecules that store and convey genetic information, but can also function as enzymes.

While the transfer of sequence information between two different classes of nucleic acid-like molecules-between RNA and DNA, for example-is straightforward because it relies on the one-to-one correspondence of the double helix pairing, transferring catalytic function is significantly more difficult because function cannot be conveyed sequentially. The present study demonstrates that the "evolutionary conversion" of an RNA enzyme to a DNA enzyme with the same function is possible, however, through the acquisition of a few critical mutations.

The study was released in an advance online version of the journal Chemistry & Biology.

Scripps Research Professor Gerald F. Joyce, a member of the Skaggs Institute for Chemical Biology whose laboratory conducted the study, said, "During early life on earth both genetic information and catalytic function were thought to reside only in RNA. In our study, the evolutionary transition from an RNA to a DNA enzyme represents a genuine change, rather than a simple expansion, of the chemical basis for catalytic function. This means that similar evolutionary pathways may exist between other classes of nucleic acid-like molecules. These findings could help answer some fundamental questions concerning the basic structure of life and how it evolved over time."

As Francis Crick, the Nobel laureate who, along with James Watson uncovered the double helix structure of DNA, articulated in 1970, all known organisms operate according to the central dogma of molecular biology-that the transfer of sequential genetic information proceeds from nucleic acid to nucleic acid, and from nucleic acid to protein. But a far different situation exists with regard to the transfer of catalytic function, which does not occur sequentially in contemporary biology. The new study shows that catalytic function can be transmitted sequentially between two different nucleic acid-like molecules, suggesting how it might have been conveyed from pre-RNA molecules to RNA during the simpler pre-RNA world period.

There are several candidates for the initial pre-RNA molecule, all of which have the ability to form base-paired structures with themselves and with RNA. Cross-pairing would allow genetic information to be transferred from these pre-RNA molecules to RNA. The catalytic function of these early enzymes might have been transferred to a corresponding RNA enzyme following the acquisition of a few critical mutations, the study said, just as the evolutionary change of a ribozyme to a deoxyribozyme with the same or similar catalytic functions might also have occurred through random mutation and selection.

For the study, an RNA ribozyme was converted to a corresponding deoxyribozyme through in vitro evolution. The ribozyme was first prepared as a DNA molecule of the same RNA sequence but with no detectable catalytic activity. A large number of randomized variations of this DNA were prepared, and repeated cycles of in vitro evolution were carried out. The result was a deoxyribozyme with about the same level of catalytic activity as the original ribozyme.

"The use of in vitro evolution provides the means to convert a ribozyme to a corresponding deoxyribozyme rapidly," Joyce said. "In the laboratory these procedures allow us to carry out many generations of test tube evolution. The resulting molecules have interesting catalytic properties, they teach us something new about evolution, and they have potential application as therapeutic and diagnostic agents."

Other authors of the study include Natasha Paul and Greg Springsteen. The study was supported by the National Aeronautics and Space Administration, the National Institutes of Health, and Johnson & Johnson Research.
Rice Bioengineers Pioneer Techniques For Knee Repair
A breakthrough self-assembly technique for growing replacement cartilage offers the first hope of replacing the entire articular surface of knees damaged by arthritis. The technique, developed at Rice University's Musculoskeletal Bioengineering Laboratory, is described in this month's issue of the journal Tissue Engineering

This has significant ramifications because we are now beginning to talk, for the first time, about the potential treatment of entire arthritic joints and not just small defects," said lead researcher and lab director Kyriacos Athanasiou, the Karl F. Hasselmann Professor of Bioengineering.

Athanasiou's new self-assembly method involves a break from conventional wisdom in bioengineering; almost all previous attempts to grow replacement transplant tissues involved the use of biodegradable implants that are seeded with donor cells and growth factors. These implants, which engineers refer to as scaffolds, foster the tissue growth process by acting as a template for new growth, but they always present a risk of toxicity due to the fact that they are made of materials that aren't naturally found in the body.

In the newly reported findings, Athanasiou and postdoctoral researcher Jerry Hu, using nothing but donor cells, grew dime-sized disks of cartilage with properties approaching those of native tissue. In a follow-up study due for publication soon, graduate student Christopher Revell refined the process to produce disks that are virtually identical to native tissue in terms of both mechanical and biochemical makeup. In a third, and perhaps most impressive breakthrough, Athanasiou and Hu used the self-assembly approach to grow the entire articular surface of the distal femur. Each of these unbroken samples were tailored three-dimensionally to fit a specific rabbit femur.

"If you told me 10 years ago that we would be making entire articular end caps via self assembly I would have said you were crazy," said Athanasiou. "The fact that we can do this is an indication of how far the discipline of tissue engineering has progressed."

Unlike cartilage, most tissues in our bodies — including skin, blood vessels and bone — regenerate themselves constantly. Tissue engineers try to capitalize on the body's own regenerative powers to grow replacement tissues that can be transplanted without risk of rejection. Donor cells from the patient are used as a starting place to eliminate rejection risks.

Most tissue engineering involves honeycombed plastic templates or hydrogels called scaffolds that are used to guide colonies of donor cells. Donor cells can be either adult stem cells or other immature cells. Athanasiou's latest work was done using chondrocytes, or cartilage cells.

Athanasiou, a former president of the international Biomedical Engineering Society, helped pioneer the development of coin-sized scaffolds in the early 1990s that are now the state-of-the-art clinical option for repairing small defects in articular knee cartilage.

His lab is also working on techniques to grow replacement knee menisci, the kidney shaped wedges of cartilage that sit between the femur and tibia and absorb the compressive shock that the bones undergo during walking and running. Over the past 18 months, he and his students Adam Aufderheide and Gwen Hoben have perfected methods of growing meniscus-shaped pieces of cartilage, but they are still trying to perfect the mechanical strength of the engineered meniscus tissue, which must be able to withstand up to an astounding 2,400 pounds per square inch of compressive pressure.

Athanasiou's research is funded by Rice University and the National Institutes of Health.

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Study: Enzyme inhibitors block SARS virus

Posted by tumicrobiology on March 28, 2006

Scientists at the Scripps Research Institute in La Jolla, Calif., and in Taiwan have found enzyme inhibitors that can block replication of the SARS virus.

Study leader Chi-Huey Wong of the Skaggs Institute of Chemical Biology and director of the Scripps Research lab said the finding is an important step in developing a drug treatment for Severe Acute Respiratory Syndrome.

"We have been working on the problem of SARS since the epidemic started in 2003," Wong said. "This new class of inhibitors represents the most potent SARS virus protease inhibitors known today."

SARS emerged in rural China in 2002 and eventually spread to 32 nations, according to the World Health Organization. SARS is caused by a ring-shaped virus known as a coronavirus and suspected of originating in animal populations before migrating to humans.

There is no effective treatment or vaccine.

The study was conducted at Scripps Research, the Genomics Research Center in Taiwan, and the National Taiwan University. It appears in the current issue of the journal Chemistry and Biology.

Copyright 2006 by United Press International. All Rights Reserved.

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Scientists Discover Interplay Between Genes

Posted by tumicrobiology on March 28, 2006

New evidence from open-sea experiments shows there's a constant shuffling of genetic material going on among the ocean's tiny plankton. It happens via ocean-dwelling viruses, scientists report this week in the journal Science.

Conducted by biological oceanographers Sallie Chisholm and her colleagues at the Massachusetts Institute of Technology, the research is uncovering a new facet of evolution and helping scientists see how microbes exploit changing conditions, such as altered light, temperature and nutrients.

"These results tell us that even the smallest organisms show genetic variation related to the environment in which they exist," said Philip Taylor, director of the National Science Foundation (NSF)'s biological oceanography program, which funded the research.

In addition to NSF, support for the research came from the Gordon and Betty Moore Foundation and from the U.S. Department of Energy.

"Our image of ocean microbes and their role in planetary maintenance is changing," Chisholm said. "We no longer think of the microbial community as being made up of species that have a fixed genetic make-up. Rather, it is a collection of genes, some of which are shared by all microbes and contain the information that drives their core metabolism, and others that are more mobile, which can be found in unique combinations in different microbes."

The distributors or carriers of new genes, the scientists suspect, are the massive numbers of viruses also known to exist in seawater. Some of them are adept at infecting ocean microbes like Prochlorococcus, the sea's most abundant plankton species. The ocean viruses, which carry their own genes as well as transport others, provide a way of transferring genes from old cells into new ones.

"We're beginning to get a picture of gene diversity and gene flow in Prochlorococcus," Chisholm said. "These photosynthesizing bacteria form an important part of the food chain in the oceans, supply some of the oxygen we breathe, and play a role in modulating climate. It's important that we understand what regulates their populations. Genetic diversity seems to be an important factor."

In one report, Chisholm and scientist Maureen Coleman suggest that gene-swapping in ocean microbes resembles the flow of genes already known to occur among disease-causing bacteria. In an ocean habitat, the exchange offers marine microbes a diverse palette of potential gene combinations, each of which might be best suited for a particular environment. "This would allow the overall population to persist despite complex and unpredictable environmental changes," said Chisholm.

A second report, by Zackary Johnson and Erik Zinser, compares where Prochlorococcus microbes are found with the conditions under which they thrive. These geographic patterns relate to environmental variables such as temperature, predators, light and nutrients.

Chisholm is trying to learn how the microbes function as a system in which they have co-evolved with each other, and with the chemistry and physics of the oceans. The studies show that all Prochlorococcus strains are very closely related, yet they display an array of physiologies and genetic diversity, Chisholm said.

"Genetic diversity is at the heart of the extraordinary stability of Prochlorococcus in the oceans, which maintain steady population sizes over vast regions of the sea," she said.

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Too Much Or Too Little Sleep Increases Diabetes Risk

Posted by tumicrobiology on March 27, 2006

Men who sleep too much or too little are at an increased risk of developing Type 2 diabetes, according to a study by the New England Research Institutes in collaboration with Yale School of Medicine researchers.

The data published in the March issue of Diabetes Care were obtained from 1,709 men, 40 to 70 years old. The men were enrolled in the Massachusetts Male Aging Study and were followed for 15 years with home visits, a health questionnaire and blood samples.

Six to eight hours of sleep was found to be most healthy. In contrast, men who reported they slept between five and six hours per night were twice as likely to develop diabetes and men who slept more than eight hours per night were three times as likely to develop diabetes, according to the lead author, H. Klar Yaggi, M.D., professor in Yale's Department of Internal Medicine, pulmonary section. Previous data from the Nurses Health Study have shown similar results in women.

"These elevated risks remained after adjustment for age, hypertension, smoking status, self-rated health status and education," Yaggi said.

He said researchers are just beginning to recognize the hormonal and metabolic implications of too little sleep. Among the documented effects, Yaggi said, are striking alterations in metabolic and endocrine function including decreased carbohydrate tolerance, insulin resistance, and lower levels of the hormone leptin leading to obesity. The mechanisms by which long sleep duration increase diabetes risk requires further investigation.

"There is a lot of interest in determining whether sleep disturbances such as a reduced amount of sleep or disorders like sleep apnea may actually worsen the metabolic syndrome," said Yaggi. Metabolic syndrome is a cluster of risk factors including high blood pressure, obesity, high cholesterol and insulin resistance which increase the risk for heart disease and stroke.

Co-authors include Andre Araujo and John McKinlay. The research was supported in part by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Disorders, the Yale Mentored Clinical Research Scholars Program from the National Center for Research Resources, and a career development award from the Veterans Affairs Health Services and Research and Development Service.

Diabetes Care 29: 657-661 (March 2006)

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Diagnostic blood test inventor dies

Posted by tumicrobiology on March 27, 2006

LONDON, March 27 (UPI) — British immunologist Robin Coombs, inventor of a widely used blood test named for him, has died at the age of 85.

Coombs invented the test that's used to diagnose anemia and to test for the presence of antigens in Rh disease, which affects about 4,000 babies a year because the mother's blood is incompatible with that of her fetus.

The British Society for Immunology, a group he helped found, reported Coombs died Jan. 25, but his death was not widely reported in the British press until this month, The New York Times said Monday.

Robert Royston Amos Coombs was born in London and grew up in South Africa and spent most of his academic career at Cambridge University, retiring during the late 1980's.

He is survived by his wife, Anne; a son, Robert; a daughter, Rosalind; and four grandchildren.

Copyright 2006 by United Press International. All Rights Reserved.

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Cell Barrier Shows Why Bird Flu Not So Easily Spread Among Humans

Posted by tumicrobiology on March 27, 2006

Although more than 100 people have been infected with the H5N1 avian influenza virus, mostly from close contact with infected poultry, the fact that the virus does not spread easily from its pioneering human hosts to other humans has been a biomedical puzzle.

Now, a study of cells in the human respiratory tract reveals a simple anatomical difference in the cells of the system that makes it difficult for the virus to jump from human to human.

The finding, reported March 22 in the journal Nature, is important because it demonstrates a requisite characteristic for the virus to equip itself to easily infect humans, the key development required for the virus to assume pandemic proportions.

The new report, by a research group led by University of Wisconsin-Madison virologist Yoshihiro Kawaoka, describes experiments using tissue from humans that showed that only cells deep within the respiratory system have the surface molecule or receptor that is the key that permits the avian flu virus to enter a cell.

Flu viruses, like many other types of viruses, require access to the cells of their hosts to effectively reproduce. If they cannot enter a cell, they are unable to make infectious particles that infect other cells – or other hosts.
"Our findings provide a rational explanation for why H5N1 viruses rarely infect and spread from human to human, although they can replicate efficiently in the lungs," the authors of the study write in the Nature report.

By looking at human tissues, Kawaoka's group noted that the cells in the upper portions of the respiratory system lacked the surface receptors that enable avian H5N1 virus to dock with the cell. Receptors are molecules on the surface of cells that act like a lock. A virus with a complementary binding molecule – the key – can use the surface receptor to gain access to the cell. Once inside, it can multiply and infect other cells.

"Deep in the respiratory system, (cell) receptors for avian viruses, including avian H5N1 viruses, are present," explains Kawaoka, who also holds an appointment at the University of Tokyo. "But these receptors are rare in the upper portion of the respiratory system. For the viruses to be transmitted efficiently, they have to multiply in the upper portion of the respiratory system so that they can be transmitted by coughing and sneezing."

The upshot of the new finding, says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine, is that existing strains of bird flu must undergo key genetic changes to become the type of flu pathogen most feared by biomedical scientists.

"No one knows whether the virus will evolve into a pandemic strain, but flu viruses constantly change," Kawaoka says. "Certainly, multiple mutations need to be accumulated for the H5N1 virus to become a pandemic strain."

The finding suggests that scientists and public health agencies worldwide may have more time to prepare for an eventual pandemic of avian influenza. Periodically, animal forms of influenza such as bird flu evolve to become highly contagious human pathogens.

Most scientists agree a pandemic of avian influenza will occur at some time. The worst-case scenario would be a form of influenza similar to the strain of 1918 that killed between 30 million and 50 million people globally.

The new work may also help scientists keep track of evolving strains of influenza and provide earlier warning of potential pandemics. For the H5N1 strain of flu virus to evolve to a pathogen easily transmissible from one human to another, changes need to occur in the virus' hemagglutinin surface protein – a molecule embedded in the virus membrane – to recognize human receptors, Kawaoka says.

"Mutations in the hemagglutinin for avian H5N1 viruses to recognize human receptors are needed for the virus to become a pandemic strain," Kawaoka explains.

Viruses isolated from humans infected with avian flu can thus be monitored in a way to provide more advance warning of a potential pandemic.

"Identification of H5N1 viruses with the ability to recognize human receptors would bring us one step closer to a pandemic strain," says Kawaoka. "Recognition of human receptors can serve as molecular markers for the pandemic potential of the isolates."

The new study was conducted in collaboration with Kyoko Shinya and Shinya Yamada of the University of Tokyo; Masahito Ebina of the Institute of Development, Aging and Cancer; Masao Ono of Tohoku University; and Noriyuki Kasai of the Institute for Animal Experimentation in Japan.

Source: University Of Wisconsin-Madison


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Study Shows That Cells Have A Natural

Posted by tumicrobiology on March 27, 2006

Scientists here have discovered a previously unknown mechanism that cells use to fight off the human immunodeficiency virus (HIV), the cause of AIDS.

The findings indicate that two proteins that normally help repair cellular DNA can also destroy the DNA made by HIV after it enters a human cell. This HIV DNA is essential for the virus to survive and reproduce.

The study was led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and published in the Proceedings of the National Academy of Sciences.

The findings could lead to a possible new strategy for treating HIV infection and AIDS, one that might complement current therapies and would probably be less susceptible to viral drug resistance – an increasingly urgent dilemma for patients and doctors.

Currently, doctors treat people with AIDS using combinations of drugs that target the virus itself. These drugs do not eliminate HIV from the body, but they do block its ability to reproduce and spread, and they restore most people with AIDS to good health.

In time, however, HIV can develop mutations that render those drugs ineffective.

“Our findings identify a new potential drug target, one that involves a natural host defense,” says principal investigator Richard Fishel, professor of molecular virology, immunology and molecular genetics and a researcher with the OSUCCC – James. “HIV treatments that target cellular components should be far less likely to develop resistance.”

Fishel's laboratory colleague and first author Kristine Yoder discovered the role of the cellular repair proteins while trying to answer a different question.

Before HIV infects a cell, it carries its genetic material in the form of RNA, or ribonucleic acid. Once inside a cell, the virus makes a copy of its genes in the form of DNA. This DNA copy – known as cDNA – then travels to the cell nucleus. There, it becomes inserted, or integrated, into the cell's DNA. There it is known as a provirus, and it will generate new HIV in an infected patient and eventually cause AIDS.

The process of integration, which is absolutely required for a productive infection, begins with the help of an enzyme, integrase, which is supplied by HIV. But the job is finished by DNA repair enzymes provided by the host cell.

Yoder originally wanted to identify which repair enzymes were involved.

During these experiments, Yoder learned that cells with high levels of two proteins called XPB and XPD had lower levels of HIV provirus in their chromosomes. Both proteins help the cell repair damaged DNA.

Yoder, Fishel and their collaborators then introduced mutations into the genes for the two proteins, which crippled the proteins' ability to repair DNA. When cells with these mutations were then infected with HIV, they showed higher levels of provirus in their chromosomes.

“When we weakened a DNA repair pathway, we got more integration of the provirus,” Yoder says. “This was a total surprise.”

Next, the researchers wanted to learn whether the normal cells used in the study had lower proviral levels because they were making less HIV cDNA or because the HIV cDNA was being destroyed before it integrated.

To answer that question, the researchers used antiretroviral drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). These drugs prevent HIV from making the cDNA copy of its RNA genetic material. The researchers exposed newly infected cells to the drugs and then measured changes in the amount of cDNA over time.

These experiments showed that the cDNA was destroyed faster in cells with normal XPB and XPD compared to cells with mutant XPB or XPD. Cells with normal XPB protein lost half their proviral DNA after 4.6 hours, while cells with low levels of the protein lost half after about 7.7 hours. Similarly, cells with normal XPD protein lost half the proviral DNA after 3.5 hours, while cells with mutated protein lost half after five hours.

These experiments also showed that the two proteins destroyed the HIV cDNA before it is integrated into the chromosome.

“Overall, our results indicate that these two DNA repair proteins participate in the destruction of HIV cDNA in cells,” Fishel says. “This process reduces the pool of HIV cDNA that can integrate into host chromosomes, thereby protecting cells from infection.”

The researchers are now working to learn how the proteins destroy the HIV cDNA. These studies could lead to drugs that might help the proteins destroy more HIV cDNA and in shorter time.

Source: Ohio State University

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Liaison nominated

Posted by tumicrobiology on March 24, 2006

Dear all,
TU Microbiology Discussion Forum (TUMDF) nominates Mr. Keshav P Koirala as its liaison.

We will announce nomination of volunteers in the recent future. For that, we are looking forward towards your approach.

If you have any comment on our nomination, please feel free to make that public by posting here.

Gaffer, TUMDF

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UW-Madison Engineers Squeeze Secrets From Proteins

Posted by tumicrobiology on March 24, 2006

Proteins, one of the basic components of living things, are among the most studied molecules in biochemistry. Understanding how proteins form or “fold” from sequenced strings of amino acids has long been one of the grand challenges of biology.



Depictions of proteins used in the study showing the different secondary and tertiary structures investigated: (a) the all-beta, C-terminal domain of protein G (16 residues of 2GB1), (b) an all-alpha fragment of protein A (1BDD), (c) the alpha/beta protein G (2GB1), and (d) the mainly-beta, SH3 domain of the SRC protein kinase (1SRL). (Image courtesy of University of Wisconsin-Madison, College of Engineering) 


A common belief holds that the more proteins are confined by their environment, the more stable – or less likely to unfold – they become. Now, as reported on the cover of the March issue of Biophysical Journal, a team of chemical and biological engineers from UW-Madison shows that premise to be untrue. While confinement plays an important role, other factors are also at play.

“Most research in this area looked at proteins in free solution when in fact, most proteins are confined in some way,” says Juan de Pablo, a chemical and biological engineer at the University of Wisconsin-Madison. “What we demonstrate for the first time is that the stability of proteins under severe confinement, which is really the relevant way of looking at them for numerous applications, depends on their shape, their size and their interactions with the environment. It is a delicate balance between the energy available to fold the protein and entropy, or it’s desire to be in the unfolded state.”

De Pablo’s research team developed a method to precisely calculate the entropy and determine how much of a protein’s stability change upon confinement to attribute to energy and how much to entropy. “This is the important part of the calculation,” de Pablo adds.

Protein stability is an incredibly important property in myriad applications, de Pablo says. Consider laundry detergent. A popular ad for detergent once claimed that “protein gets out protein.” The idea behind this is that engineered enzymes are at work in the wash breaking down elements of a stain.

“Once a protein is folded, you can actually unfold it or destabilize it, either by heating it up, or by adding solvents to the system, like urea for example, that just destroy the folded structure of the protein. How resilient the protein is to these assaults is what we often call stability,” de Pablo says. “Detergents like the ones you use to wash your clothes have enzymes that break the fat in stains. When you put you clothes in hot water in your washing machine, you want your detergents to withstand those high temperatures. So what people do is engineer enzymes that do not unfold when you put them in hot water. They design enzymes that are more stable than normal enzymes at high temperatures.”

To better understand protein folding, de Pablo’s team built computer models of proteins under different types of confinement. These models were then simulated to gain a better understand of protein stability. Working with the UW-Madison Nanoscale Science and Engineering Center (NSEC), funded by the National Science Foundation, the researchers will continue to refine their models with the goal of confining, folding and measuring the stability of proteins under more realistic conditions.

Source: University of Wisconsin-Madison

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Scientists One Step Closer To Cancer Vaccine

Posted by tumicrobiology on March 24, 2006

Scientists at Karolinska Institutet in Sweden have helped to identify a molecule that can be used as a vaccination agent against growing cancer tumours. Although the results are so far based on animal experiments, they point to new methods of treating metastases.

The results are presented in the online edition of the prestigious scientific journal Nature Medicine, and represent the collaborative efforts of researchers at KI and Leiden University Medical Centre in Holland.

The study analysed an immunological cell, a T cell, which recognises other cells with defects common to metastasing ones. These defects (which are found in MHC class 1 molecules) allow the tumour cell to evade the “conventional” T cell-mediated immune defence.

The researchers have identified a short peptide molecule that the T cell in the study recognises. Using this peptide, the researchers can vaccinate and protect against the spread of tumours from different tissues, including melanoma, colon cancer, lymphoma, and fibrosarcoma.

“So far we’ve only conducted research on mice, so it’s too early to get out hopes up too much,” says research scientist Elisabeth Wolpert at the Microbiology and Tumour Biology Centre. “However, the study does point towards new possible ways of developing a treatment for advanced tumour diseases.”

The newly published study is a continuation of an original discovery that first identified the TEIPP-T cell and that was presented in Ms Wolpert’s doctoral thesis at Karolinska Institutet in 1998.

The spread of tumours, or metastases, is the most common cause of death from cancer.

Source: Karolinska Institutet

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“Therapy Against Serious Side Effects Of Smallpox Vaccine”

Posted by tumicrobiology on March 24, 2006

Smallpox is considered a potential terrorist weapon, but millions of people in the United States are currently advised not to get a vaccine to the disease because they are susceptible to developing a severe adverse reaction. Researchers at National Jewish Medical and Research Center report in the March issue of Immunity that a deficiency in the innate immune response may pre-dispose patients with atopic dermatitis, or eczema, to developing the skin condition eczema vaccinatum after vaccination. The findings suggest potential therapeutic targets, which may reduce the risk of this devastating side effect.

“I believe these findings could have a significant impact on our ability to vaccinate individuals with eczema and better protect them against potential bio-terrorist attacks involving smallpox,” said Michael Howell, Ph.D., first author of the report and Instructor of Pediatrics at National Jewish Medical and Research Center. “We identify potential therapies, which should be further tested to determine if they can effectively and safely protect susceptible patients against eczema vaccinatum.”

Eczema vaccinatum occurs when the vaccinia virus, which is currently used for the smallpox vaccine, replicates uncontrollably and circulates through the entire body. Eczema vaccinatum kills 1 to 6 percent of those affected. Up to 30 percent of children younger than 2 years of age with the disease die. It is also possible that atopic dermatitis patients can develop eczema vaccinatum even if they don’t get the vaccine, but come into close personal contact with people who recently received the vaccine.

Approximately 17 percent of children in the United States are diagnosed with atopic dermatitis, suggesting that close to 50 million people in the United States face an increased risk of eczema vaccinatum following the smallpox vaccine. The U.S. Centers for Disease Control currently recommends that individuals with atopic dermatitis, and those who come into close contact with them, do not receive the live vaccine due to potential adverse reactions. This accounts for approximately 50% of the population in the United States. In case of an actual smallpox outbreak, they would likely receive the vaccine and face the increased risk of developing eczema vaccinatum.

The National Jewish research team, led by Donald Leung, M.D., Ph.D., Edelstein Family Chair of Pediatric Allergy-Immunology, had previously reported that atopic dermatitis patients have lower levels of disease-fighting antimicrobial peptides in their skin than people without the disease. They also reported that one particular antimicrobial peptide, called LL-37, could kill vaccinia virus when it is grown in cell culture.

In their current report, the researchers found that lower levels of LL-37 in the skin of patients with atopic dermatitis did indeed allow the uncontrolled growth of vaccinia virus. Skin cells from atopic dermatitis patients failed to increase LL-37 production in response to the vaccinia virus infection, while skin cells from healthy controls and patients with the skin disease psoriasis samples did ramp up LL-37 production. When the researchers added LL-37 to the infected atopic dermatitis skin cells, vaccinia virus growth slowed significantly.

“It is becoming increasingly clear how important antimicrobial peptides are in immune defense,” said Dr. Leung. “They are part of the fast-acting, innate immune response. Because atopic dermatitis patients fail to mount a vigorous innate response with antimicrobial peptides, vaccinia virus infection gets well established and the slower adaptive immune response cannot eradicate it.”

Atopic dermatitis patients have high levels of signaling molecules interleukin-4 (IL-4) and interleukin-13 (IL-13) in their skin. The researchers found that IL-4 and IL-13 inhibited the production of LL-37 in atopic dermatitis patients. When they added antibodies to neutralize the two interleukins, levels of LL-37 rose in atopic dermatitis patients, and the vaccinia virus infection was controlled.

“Antibodies or other drugs that neutralize IL-4 and IL-13 are currently being developed,” said Dr. Howell. “We think they should be evaluated as potential therapies that could be given at the same time as the smallpox vaccine as protection against potentially fatal side effects.”

Source: National Jewish Medical and Research Center

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Mobile animal diagnostic lab developed

Posted by tumicrobiology on March 24, 2006

Texas A&M University scientists say they’ve developed a mobile diagnostic laboratory to test animals in the event of a disease outbreak.

The executive director of the Texas Veterinary Medical Diagnostic Laboratory, Dr. Lelve Gayle, said a rapid, massive response by health officials is critical during a disease outbreak — even if the patients are animals.

The lab — housed in a trailer about the size of a recreational vehicle — will enable the diagnostic laboratory to expand quickly its capability to respond to an animal disease outbreak such as avian flu or livestock diseases not presently in the United States, Gayle said.

The mobile lab can be ready to process blood and tissue samples for animal diseases within 24-48 hours. The samples are then sent to the main laboratory in College Station, Texas, for testing.

The trailer has biosafety level-three rating, which means it had to pass stringent standards to keep disease organisms from escaping into the environment.

If a disease is suspected, laboratory testing is required — and Gayle’s goal is to have the mobile laboratory ready to test samples within two hours, seven days a week.

Copyright 2006 by United Press International. All Rights Reserved.

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Analysis: Ebola test urgent amid globalism

Posted by tumicrobiology on March 24, 2006



A rapid, inexpensive blood test that can identify 10 viral hemorrhagic diseases, including the Ebola virus and yellow fever, has been developed by researchers at the Mailman School of Public Health at Columbia University. The measure is being used in a surveillance capacity at the current time, and will be available for both stationary and mobile laboratory use once a commercial partner can be found. “Global travel and global trade means that everything goes everywhere,” W. Ian Lipkin, director of the Greene Infectious Disease Laboratory at Mailman, told United Press International. “SARS proved that. It started in China and moved to Toronto. While most of these diseases are endemic to Africa, a case of Ebola virus was diagnosed five years ago in Reston, VA after a shipment of animals arrived from the Philippines,” he said. Lipkin noted that the new test developed by the Columbia researchers marks an important breakthrough in battling the cadre of exotic-sounding, but increasingly well-traveled maladies. “Diagnosis and isolation are the key to stopping an outbreak. Up until now there were no good tests for any of these problems and the disease had to become full blown before it could be recognized,” he said. “Now we can test sick people who have recently traveled in an area where a disease is endemic, or handled animals from that area, and make a diagnosis before they have a chance to spread the virus,” Lipkin said. According to a MSPH, the research team that devised the new test was led by Thomas Briese and represented an international coalition of laboratories from the United States, Canada, Europe, South Africa, India and China, the same group that first worked together on the SARS outbreak in 2003. The group decided to stay together and tackle other global health problems, and the test for hemorrhagic fevers is the result. Diagnostic tests for diarrheal diseases and meningitis/encephalitis are being developed, and the respiratory virus test developed for SARS and other viral respiratory pathogens is also in use. The new test that emerged from the collaboration takes two hours to simultaneously diagnose a virtual plethora of deadly pathogens, including yellow fever, Ebola Zaire virus, Ebola Sudan virus, Marburg virus, Lassa virus, Rift Valley fever, Crimean-Congo hemorrhagic fever, Hantaan virus, Seoul virus and Kyansanur Forest disease. A combination of technologies, including polymerase chain reaction, genetic amplification and mass spectroscopy, are involved, but the cost of the test is only $5 to $10. Lipkin told UPI that all the hemorrhagic diseases covered by the test are fatal, quickly become epidemic in humans and their early symptoms all resemble mild flu. He noted that the animal connection was an important one because 70 percent of all infectious diseases (such as HIV, Lyme disease and West Nile virus) begin in animals and jump to humans, including the viruses that the new test covers. Rona Hirschberg, senior program officer at NIAID, told UPI that the technology, if available decades ago, could have changed the course of history in the battle with another infamous filler. “If we had known about HIV in chimps back in the seventies, we would have had diagnostic tests and possible treatments ready and could have slowed the epidemic,” Lipkin responded. “The diseases our new test covers have already moved to humans, but being able to diagnose them quickly will allow us to stop them before they can devastate the world’s population the way HIV has done.” Briese, Lipkin and the coalition will describe their work in the April 2006 issue of the Centers for Disease Control and Prevention’s Emerging Infectious Diseases. Copyright 2006 by United Press International. All Rights Reserved.

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Ocean virus identified in human blood

Posted by tumicrobiology on March 24, 2006

Scientists say a virus of ocean origin that can cause a range of diseases in several animal species has been found in human blood samples.
The virus, or antibodies to it, was found most often in the blood of individuals with liver damage, or hepatitis of unknown cause related to blood exposure.
Scientists from Oregon State University, Eastern Virginia Medical School, and AVI BioPharma say the association between viral infection and the presence of a disease of unknown cause does not prove cause and effect. But they say the data are intriguing and raise important new questions.
The researchers say further study is needed to establish proof that infection with the virus in humans is causing liver damage or some other problems, which may include encephalitis and spontaneous abortion.
The viral group being studied is the genus Vesivirus, one of four genera in the Caliciviridae viral family. Some caliciviruses cause disease in humans, such as the Norwalk virus that causes gastroenteritis. Other caliciviruses cause a wide range of disease in other animal species.
The study appears in the online edition of the Journal of Medical Virology.
Copyright 2006 by United Press International.

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“Cell Engineering May Lead To Mad Cow Prevention”

Posted by tumicrobiology on March 23, 2006

Researchers at Texas A&M University have successfully “knocked down” the expression of possible disease-causing genes in a cloned goat fetus, perhaps paving the way for breeding disease resistance in other animals, even those genes that might cause bovine spongiform encephalopathy (BSE), commonly known as Mad Cow Disease.

Researchers Mark Westhusin and Charles Long in Texas A&M’s College of Veterinary Medicine & Biomedical Sciences, working with fellow scientists Greg Hannon, Michael Golding and Michelle Carmell at the Howard Hughes Medical Institute’s Cold Spring Harbor Laboratory, successfully utilized genetic engineering to produce a goat cell line in which the gene encoding for prion protein (PrP) was targeted for silencing by a process known as RNA interference. They then utilized these cells for nuclear transfer to produce a cloned, transgenic goat fetus which exhibited a greater than 90 percent knock down of PrP. Previous studies involving mice in which the PrP gene has been silenced have demonstrated the animals to be resistant to prion-mediated diseases such as BSE.

Their work is published in the current Proceedings of the National Academy of Sciences.

Their success raises the possibility of introducing the same technology into cattle to prevent numerous diseases. “The exciting part is that we may be able to use this technology to prevent other diseases from ever starting,” Westhusin explains.

“We were able to knock down the genes that are involved with diseases in goats. In cattle, the disease that would most likely be targeted would be BSE, although there are numerous other genes that could be targeted to produce animals resistant to a variety of diseases. Moreover, the success raises possibilities to develop similar disease resistance strategies in other animal species,” Westhusin adds.

BSE, or Mad Cow Disease, is a fatal brain-wasting disease first identified in the United Kingdom in 1986. BSE affects a cow’s nervous system and causes the animal to lose much of its movement before it eventually dies.

More than 180,000 cases of BSE have been confirmed worldwide, including recent cases in the United States. The disease can be passed to humans, and more than 100 such cases have been confirmed, most of those in England.

“The next step is to try and avoid the cloning process – to skip that step if possible in developing the disease resistant animals,” Westhusin says. “That’s where more research is going to be needed and where the process goes from here.”

Westhusin has been involved in several cloning “firsts,” among them the first cloning of a cat in 2002 and a white tailed deer in 2004.

The team’s project was funded by the National Institutes of Health and the U.S. Department of Agriculture.

Source: Texas A&M University

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Plants’ potential to control HIV?

Posted by tumicrobiology on March 20, 2006

Scientists have developed a new kind of molecule which they believe could ultimately lead to the development of a vaccine against HIV using genetically modified tobacco. Writing in Plant Biotechnology Journal, Dr Patricia Obregon and colleagues from St George’s, University of London along with researchers at the University of Warwick say they have overcome a major barrier that has so far frustrated attempts to turn plants into economically viable “bioreactors” for vaccines.By creating fusion molecules, the researchers have found a way to make plants produce more of the molecules (antigens) needed for vaccines. At the same time, they may also have discovered a way of producing better targeted vaccines. Obregon and her colleagues in Dr Julian Ma’s laboratory are working with the p24 core protein of the Human Immunodeficiency Virus (HIV). This protein plays a central role in eliciting the immune response to HIV infection, and is therefore likely to be an integral part of any multicomponent vaccine for HIV.Plants have already been used to produce many types of vaccine molecules, but a consistent problem has been achieving adequate levels of protein expression in order to make them viable as bioreactors for vaccines.

Obregon and her colleagues have found a way to significantly boost HIV-1 p24 protein production in plants by producing an entirely new molecule — a fusion of the HIV-1 p24 protein and part of another protein, human immunoglobulin A (IgA) – a major component of the immune system. The team found that the HIV-1p24 antigen produced in this way elicited appropriate immune response in mice.

The results have important implications for the economic viability of using plants as bioreactors to produce vaccines against HIV and other diseases. According to Obregon: “Using antibody-antigen fusion molecules may represent a generic strategy to increase the expression of recombinant proteins in plants. It could open the door to cheaper biopharmaceuticals. Plant-derived pharmaceuticals are of great interest because of their enormous potential for economy and scale of production. This technology could lead to production of modern medicines that will also be accessible to poor populations in developing countries — which is where these medicines are needed the most.”

The results could also lead to the development of more effective vaccines. By using specific immunoglobulin sequences in the fusion molecule, antigens could be targeted to specific cells in the immune system, the authors say.                                                                    

Source: Blackwell Publishing Ltd.

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Minor Mutations In Avian Flu Virus Increase Chances Of Human Infection

Posted by tumicrobiology on March 19, 2006

Scientists at The Scripps Research Institute, the Centers for Disease Control, and the Armed Forces Institute of Pathology have identified what the researchers described as a possible pathway for a particularly virulent strain of the avian flu virus H5N1 “to gain a foothold in the human population.”

The H5N1 avian influenza virus, commonly known as “bird flu,” is a highly contagious and deadly disease in poultry. So far, its spread to humans has been limited, with 177 documented severe infections, and nearly 100 deaths in Indonesia, Vietnam, Thailand, Cambodia, China, Iraq, and Turkey as of March 14, 2006, according to the World Health Organization (

“With continued outbreaks of the H5N1 virus in poultry and wild birds, further human cases are likely,” said Ian Wilson, a Scripps Research professor of molecular biology and head of the laboratory that conducted the recent study. “The potential for the emergence of a human-adapted H5 virus, either by re-assortment or mutation, is a clear threat to public health worldwide.”

Of the H5N1 strains isolated to date, the researchers looked at A/Vietnam/1203/2004 (Viet04), one of the most pathogenic H5N1 viruses studied so far. The virus was originally isolated from a 10-year-old Vietnamese boy who died from the infection in 2004. The hemagglutinin (HA) structure from the Viet04 virus was found to be closely related to the 1918 virus HA, which caused some 50 million deaths worldwide.

Using a recently developed microarray technology—hundreds of microscopic assay sites on a single small surface—the study showed that relatively small mutations can result in switching the binding site preference of the avian virus from receptors in the intestinal tract of birds to the respiratory tract of humans.These mutations, the study noted, were already “known in [some human influenza] viruses to increase binding for these receptors.”

The study was published on March 16, 2006 by ScienceXpress, the advance online version of the journal Science.

Receptor specificity for the influenza virus is controlled by the glycoprotein hemagglutinin (HA) on the virus surface. These viral HAs bind to host cell receptors containing complex glycans—carbohydrates—that in turn contain terminal sialic acids. Avian viruses prefer binding to a2-3-linked sialic acids on receptors of intestinal epithelial cells, while human viruses are usually specific for the a2-6 linkage on epithelial cells of the lungs and upper respiratory tract. Such interactions allow the virus membrane to fuse with the membrane of the host cell so that viral genetic material can be transferred to the cell.

The switch from a2-3 to a2-6 receptor specificity is a critical step in the adaptation of avian viruses to a human host and appears to be one of the reasons why most avian influenza viruses, including current avian H5 strains, are not easily transmitted from human-to-human following avian-to-human infection. However, the report did suggest that “once a foothold in a new host species is made, the virus HA can optimize its specificity to the new host.”

“Our recombinant approach to the structural analysis of the Viet04 virus showed that when we inserted HA mutations that had already been shown to shift receptor preference in H3 HAs to the human respiratory tract, the mutations increased receptor preference of the Viet04 HA towards specific human glycans that could serve as receptors on lung epithelial cells,” Wilson said. “The effect of these mutations on the Viet04 HA increases the likelihood of binding to and infection of susceptible epithelial cells.”

The study was careful to note that these results reveal only one possible route for virus adaptation. The study concluded that other, as yet “unidentified mutations” could emerge, allowing the avian virus to switch receptor specificity and make the jump to human-to-human transmission.

The glycan microarray technology, which was used to identify the mutations which could enable adaptation of H5N1 into the human population in the laboratory, could also be used to help identify new active virus strains in the field by monitoring changes in the receptor binding preference profile where infection is active, according to according to Jeremy M. Berg, the director of the National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health (NIH). The glycan microarray was developed by The Consortium for Functional Glycomics, an international group led by Scripps Research scientists and supported by the NIGMS.

“This technology allows researchers to assay hundreds of carbohydrate varieties in a single experiment,” Berg said. “The glycan microarray offers a detailed picture of viral receptor specificity that can be used to map the evolution of new human pathogenic strains, such as the H5N1 avian influenza, and could prove invaluable in the early identification of emerging viruses that could cause new epidemics.”

Other authors of the study include James Stevens of Scripps Research; Ola Blixt of Scripps Research and Glycan Array Synthesis Core-D, Consortium for Functional Glycomics; Terrence M. Tumpey, Influenza Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention; Jeffery K. Taubenberger, Department of Molecular Pathology, Armed Forces Institute of Pathology, and; James C. Paulson, Scripps Research and Glycan Array Synthesis Core-D, Consortium for Functional Glycomics.

The work was supported by the National Institute of Allergy and Infectious Disease, the National Institute of General Medical Sciences and the National Institutes of Health.

Source: Scripps Research Institute

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New Study Describes Key Protein From Highly Pathogenic H5N1 Avian Flu Virus And How It Might Mutate

Posted by tumicrobiology on March 17, 2006

The recent spread of deadly H5N1 influenza A virus among birds in Asia, Europe, and Africa has been the focus of much attention and concern worldwide–largely because of the danger that the virus will mutate into a form that will become easily transmissible from person to person.

In a March 16 article published online by Science, a research team led by scientists at The Scripps Research Institute in California reveals the structure of an H5 protein from a highly pathogenic strain of H5N1 avian influenza virus and compares this structure to the same proteins from other pandemic influenza A viruses, including the deadly 1918 virus.

Further, they discuss a potential route whereby H5N1 might mutate and acquire human specificity. The work also describes the application of a new technology called glycan microarrays, which can be used to determine whether H5 proteins from various strains of H5N1 target human or bird cells and map how their specificity is changing.

ARTICLE: “Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus,” James Stevens et al. Science DOI: 10.1126/science.1124513 (2006).

NIAID and NIGMS are components of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies. NIGMS supports basic biomedical research that is the foundation for advances in disease diagnosis, treatment, and prevention.

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Posted by tumicrobiology on March 13, 2006

Hello TU Microbiologists,
We are going to nominate a liason and some volunteers in near future. If you have any recommendations, or if you yourself want to be nominated feel free to write to us.
Gaffer, TUMDF

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Researchers To Study Effectiveness Of Stem Cell Transplant In Human Brain

Posted by tumicrobiology on March 11, 2006

Source: Oregon Health & Science University

Researchers in Doernbecher Children’s Hospital at Oregon Health & Science University will begin a Phase I clinical trial using stem cells in infants and children with a rare neurodegenerative disorder that affects infants and children. The groundbreaking trial will test whether HuCNS-SC(TM), a proprietary human central nervous stem cell product developed by StemCells, Inc. is safe, and whether it can slow the progression of two forms of neuronal ceroid lipofuscinosis (NCL), a devastating disease that is always fatal. NCL is part of a group of disorders often referred to as Batten disease.

“NCL is a heartbreaking and devastating diagnosis for children and their families,” said Robert D. Steiner, M.D., F.A.A.P., F.A.C.M.G., vice chairman of pediatric research, head of the Division of Metabolism and the study’s principal investigator at Doernbecher Children’s Hospital, OHSU. Steiner also is an associate professor of pediatrics, and molecular and medical genetics in the OHSU School of Medicine. “While the preclinical research in the laboratory and in animals is promising, it is important to note that this is a safety trial and, to our knowledge, purified neural stem cell transplantation has never been done before. It is our hope that stem cells will provide an important therapeutic advance for these children who have no other viable options.”

NCL is caused by mutations or changes in the genes responsible for teaching the body how to make certain enzymes. Without these enzymes or proteins, material builds up inside brain neurons and other brain cells, causing a rapidly progressive decline in mental and motor function, blindness, seizures and early death. This study addresses two forms of NCL: infantile neuronal ceroid lipofuscinosis (INCL) and late-infantile neuronal ceroid lipofuscinosis (LINCL). Tragically, children with INCL typically die before age 5 and those with LINCL typically do not live past age 12.

“If delivering stem cells directly into the human brain is safe and effective, it will, in my opinion, be a major step forward in the efforts of scientists and clinicians around the country to find new treatments with the potential to help tens of thousands of patients with degenerative brain diseases,” said co-investigator Nathan Selden, M.D., Ph.D., F.A.C.S., F.A.A.P. “I am proud that Doernbecher Children’s Hospital will be part of this effort.” Selden is Campagna Associate Professor of Pediatric Neurological Surgery and head of the Division of Pediatric Neurological Surgery, Doernbecher and OHSU School of Medicine.

Up to six children from Oregon or around the country will undergo HuCNS-SC transplantation at Doernbecher. Previous studies of mice that are missing one of the enzymes that causes NCL have shown HuCNS-SC increases the amount of the missing enzyme, reduces the amount of abnormal material in the brain and prevents the death of some brain cells. No major side effects have been reported in animals.

StemCells, Inc. received clearance from the U.S. Food and Drug Administration to initiate a Phase 1 clinical trial of HuCNS-SC in October 2005. The company believes this will be the first trial using a purified composition of neural stem cells as a potential therapeutic agent in humans.

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Secret Sex Life Of Killer Fungus

Posted by tumicrobiology on March 11, 2006

Source: University of Manchester

A fungus that causes life-threatening infections in humans may be having sex, say scientists.

Aspergillus fumigatus, a fungus that has also been linked to asthma, had always been thought to reproduce asexually.

But a study by researchers at Nottingham and Manchester universities has revealed that the fungus has a series of genes required for sexual reproduction.

The discovery, published in the science journal Current Biology, has important implications for the way diseases caused by the fungus – estimated to affect some 5,000 people in the UK each year – are treated.

“The possible presence of sex in the species is highly significant as it affects the way we try and control disease,” said Dr David Denning, of The University of Manchester.

“If the fungus does reproduce sexually as part of its life cycle, then it might evolve more rapidly to become resistant to antifungal drugs – sex might create new strains with increased ability to cause disease and infect humans.”

The research team, headed by Dr Paul Dyer at the University of Nottingham, used a number of techniques to study the fungus’s genetic make-up or genome.

The analysis of 290 specimens worldwide revealed that the fungus was composed of nearly equal proportions of two different sexes or ‘mating types’, which in theory could have sex with each other.

Further investigations, in Europe and America, showed that genes had been, or were being, exchanged between individuals of the fungus and that some key genes involved with detecting a partner were active in the fungus.

“Taken as a whole, the results indicate that the fungus has a recent evolutionary history of sexual activity and might still be having sex so far ‘unseen’ by human eyes,” said Dr Dyer.

“The sexual cycle could be a useful genetic tool for scientists to study the way in which the fungus causes disease.”

Further work is now aimed at seeing if the fungus can truly reproduce by sexual means.

Dr Dyer added: “The fungus is very common in compost heaps so these might be a hotbed of fungal sex!”

The team working on the research was headed by Paul Dyer (University of Nottingham) with lead researchers David Denning (The University of Manchester), Mathieu Paoletti (University of Nottingham) and Carla Rydholm (Duke University, USA)

The work was funded by the Biotechnology and Biological Sciences Research Council (UK), the Fungal Research Trust (UK) and Duke University (USA).

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Posted by tumicrobiology on March 9, 2006


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DNA From The Deep

Posted by tumicrobiology on March 9, 2006


What kinds of microbes live beneath the surface of the open ocean? What are they doing down there? These are the sorts of questions that MBARI researcher Chris Preston has been trying to answer in her research. But instead of using a microscope (even under a good scope, most bacteria just look like little dots or squiggles), Preston analyzes DNA from marine microbes to determine what types are present and what biochemical tricks they use to survive.


Thousands of different types of microbes inhabit every cubic centimeter of seawater. Although a few types of microbes been studied in detail, DNA studies will help scientists learn about the many species that have yet to be identified. (Image: Ed DeLong (c) 2000 MBARI)

Working with microbiologist Ed DeLong and his team at MIT, and with David Karl at the University of Hawaii, Preston recently coauthored a paper that describes the DNA of microbe communities at seven different depths in the tropical Pacific Ocean, from the surface down to 4,000 meters (about 13,000 feet). This paper was published in the January 27, 2006 issue of Science magazine.

Smaller but more numerous than marine algae, marine microbes such as bacteria and blue-green algae have huge effects on ocean chemistry and possibly even climate. Many of these organisms can’t be cultured in the laboratory, and have only recently been discovered using DNA analysis. Probably thousands of additional species have yet to be discovered or named.

Even though only a small fraction of marine microbes have been studied in detail, DeLong, Preston, and others have learned a lot by analyzing the combined DNA of all the marine microbes in a sample of seawater. The resulting data can give scientists a ‘birds-eye-view’ of entire microbial communities. DeLong first pioneered this technique about 12 years ago. In the last few years, however, technological advances have made it possible for scientists to sequence really large quantities of DNA in a matter of weeks or months. This allows biologists to study not just microbial communities as a whole, but individual groups of microbes within those communities.

For this project, Preston worked with scientists at the University of Hawaii to collect water from the open ocean about 100 kilometers (60 miles) north of the island of Oahu. This spot, the Hawaii Ocean Time Series station, was chosen because it is far from any terrestrial influences, yet its chemistry and (non-microbial) biology are relatively well studied . Because concentrations of microbes were so low in this ‘oceanic desert’ area, Preston and fellow MBARI researcher Lynne Christianson had to spend five to six hours filtering up to 600 liters (160 gallons) of seawater for each sample, in order to obtain enough microbial DNA for analysis.

One of the researchers’ overall goals was to determine how the microbes near the surface are different from those that live thousands of meters down. Not surprisingly, in samples from the sunlit waters within about 100 meters of the surface, the researchers found a lot of microbial DNA sequences that were associated with photosynthesis. This means many microbes in these waters were probably using sunlight as a source of energy. Surface samples also contained microbial DNA that was associated with movement and propulsion. This suggests that movement is important for these microbes, perhaps helping them follow chemical gradients or move from food particle to food particle.

In contrast, DNA from microbes in deeper waters suggests many survive by attaching to and breaking down particles of organic material. Such particles continually sink down from the surface waters into the deep sea, providing food for many organisms in the form of ‘marine snow.’

Perhaps the most surprising finding of this study was the large amount of DNA that came from viruses, especially in near-surface waters. Since the researchers excluded free-living viruses from their initial sample, they believe that this viral DNA must have come from viruses that had infected living bacteria. Such viruses reproduce within bacterial cells, and can actually transfer DNA from one bacterium to another. This makes the already complicated process of analyzing microbial DNA even more challenging.

Although the paper in Science describes some of the initial findings from DeLong’s team, other researchers will be analyzing their DNA sequences for years to come. As Preston explains, ‘One thing that other researchers can do is to compare our sequences with those from microbial communities in other regions of the ocean, in soil, in salty brines, or in fresh water environments. They may see similar metabolic pathways or find entirely new ones.’

In fact, just a few years ago DeLong and his colleagues did just this. They compared DNA from marine microbes to DNA from salt pond microbes (archaea) and discovered a new type of photosynthetic pigment, which they called proteorhodopsin. This eventually led to the discovery that marine microbes can obtain energy from the sun through photosynthesis. Similar breakthroughs may emerge from detailed analyses of Preston and DeLong’s seawater samples from the tropical Pacific.

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New, Quicker Tests Identify E. Coli Strains

Posted by tumicrobiology on March 6, 2006

Source: USDA / Agricultural Research Service

(January 1, 2004)

New, Quicker Tests Identify E. Coli Strains
New tests that more quickly identify dangerous strains of Escherichia coli bacteria are being developed by Agricultural Research Service scientists in Wyndmoor, Pa.

ARS microbiologist Pina M. Fratamico, at the agency’s Eastern Regional Research Center (ERRC) in Wyndmoor, is working with Pennsylvania State University to develop tests that quickly identify E. coli strains.

Certain E. coli strains, such as O157:H7, causes serious diseases, including bloody diarrhea and hemorrhagic colitis. Infections may result in serious health complications, including kidney failure. Other E. coli serogroups, including E. coli O26, O111 and O121, also cause gastrointestinal illnesses in humans.

Currently, scientists commonly use a procedure called serotyping to distinguish between different types of E. coli–some harmful, others harmless. However, this procedure is time-consuming and labor-intensive.

Fratamico, with ERRC’s Microbial Food Safety Research Unit, and her team are developing both conventional and real-time polymerase chain reaction (PCR) tests. These chemical procedures generate enough of a bacterium’s genetic material so that it can be studied and identified. With one real-time PCR reaction, four products can be amplified simultaneously and detected in “real time” as they multiply.

Scientists have little information about some individual E. coli serogroups; therefore, the number of diseases these organisms cause is likely underestimated. Fratamico is targeting genes in the E. coli O-antigen gene clusters so researchers can detect and identify specific serogroups and increase knowledge about each one’s potency.

In one study, a real-time PCR assay was more sensitive than other detection methods. According to Fratamico, the U.S. Department of Agriculture’s Food Safety and Inspection Service has expressed interest in the new PCR tests for detection and confirmation of not only E. coli O157:H7, but of other E. coli strains as well.

ARS is the USDA’s chief scientific research agency.

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New, Quicker Tests Identify E. Coli Strains

Posted by tumicrobiology on March 6, 2006

Source: USDA / Agricultural Research Service

(January 1, 2004)

New, Quicker Tests Identify E. Coli Strains
New tests that more quickly identify dangerous strains of Escherichia coli bacteria are being developed by Agricultural Research Service scientists in Wyndmoor, Pa.

ARS microbiologist Pina M. Fratamico, at the agency’s Eastern Regional Research Center (ERRC) in Wyndmoor, is working with Pennsylvania State University to develop tests that quickly identify E. coli strains.

Certain E. coli strains, such as O157:H7, causes serious diseases, including bloody diarrhea and hemorrhagic colitis. Infections may result in serious health complications, including kidney failure. Other E. coli serogroups, including E. coli O26, O111 and O121, also cause gastrointestinal illnesses in humans.

Currently, scientists commonly use a procedure called serotyping to distinguish between different types of E. coli–some harmful, others harmless. However, this procedure is time-consuming and labor-intensive.

Fratamico, with ERRC’s Microbial Food Safety Research Unit, and her team are developing both conventional and real-time polymerase chain reaction (PCR) tests. These chemical procedures generate enough of a bacterium’s genetic material so that it can be studied and identified. With one real-time PCR reaction, four products can be amplified simultaneously and detected in “real time” as they multiply.

Scientists have little information about some individual E. coli serogroups; therefore, the number of diseases these organisms cause is likely underestimated. Fratamico is targeting genes in the E. coli O-antigen gene clusters so researchers can detect and identify specific serogroups and increase knowledge about each one’s potency.

In one study, a real-time PCR assay was more sensitive than other detection methods. According to Fratamico, the U.S. Department of Agriculture’s Food Safety and Inspection Service has expressed interest in the new PCR tests for detection and confirmation of not only E. coli O157:H7, but of other E. coli strains as well.

ARS is the USDA’s chief scientific research agency.

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