Joseph Morley of the University of Leicester has been awarded the Society for General Microbiology Undergraduate Microbiology Prize 2008 - an award for best performance in second year microbiology modules. This prize aims to encourage excellence in the study of microbiology by undergraduate students, and to promote scholarship in and awareness of microbiology in universities.

The Society for General Microbiology (SGM) is the largest microbiological society in Europe. It has over 5000 members of whom 75% are resident in the UK with the rest in more than 60 countries worldwide. Joseph, who is currently working on his final year research project on marine cyanophages, was awarded a cheque for £150, a certificate and one year’s free undergraduate membership of the SGM. Joseph says he is delighted to be awarded this prestigious national prize.

Patients who succumbed to influenza during the 1918 pandemic had severe lung pathology marked by extensive inflammatory infiltrate, indicating a robust immune response in the lung. Similar findings have been reported from H5N1-infected patients, raising the question as to why people expire in the presence of a strong immune response. A new paper addresses this question by characterizing the immune cell populations in the mouse lung following infection with the 1918 pandemic virus and two H5N1 viruses isolated from fatal cases. The data shows excessive immune cell infiltration in the lungs contributing to severe consolidation and tissue architecture destruction in mice infected with highly pathogenic influenza viruses, supporting the histopathological observations of lung tissue from 1918 and H5N1 fatalities. The researchers found that certain cells of the innate immune system, specifically macrophages and neutrophils, increase significantly into the mouse lung shortly following HP virus infection. Interestingly, lung macrophages and dendritic cells were shown to be susceptible to 1918 and H5N1 virus infection in vitro or ex vivo, suggesting a possible mechanism of immunopathogenesis. Identification of the precise inflammatory cells associated with lung inflammation will be important for the development of treatments that could potentially enhance or modulate host innate immune responses. While reducing virus load through anti-viral intervention remains the best treatment option for H5N1 patients, therapies that moderate immunopathology may help to reduce the high case fatality rate currently associated with this virus infection.

H5N1 and 1918 Pandemic Influenza Virus Infection Results in Early and Excessive Infiltration of Macrophages and Neutrophils in the Lungs of Mice. PLoS Pathogens, 4 (8)
Fatal human respiratory disease associated with the 1918 pandemic influenza virus and potentially pandemic H5N1 viruses is characterized by severe lung pathology, including pulmonary edema and extensive inflammatory infiltrate. Here, we quantified the cellular immune response to infection in the mouse lung by flow cytometry and demonstrate that mice infected with highly pathogenic (HP) H1N1 and H5N1 influenza viruses exhibit significantly high numbers of macrophages and neutrophils in the lungs compared to mice infected with low pathogenic (LP) viruses. Mice infected with the 1918 pandemic virus and a recent H5N1 human isolate show considerable similarities in overall lung cellularity, lung immune cell sub-population composition and cellular immune temporal dynamics. Interestingly, while these similarities were observed, the HP H5N1 virus consistently elicited significantly higher levels of pro-inflammatory cytokines in whole lungs and primary human macrophages, revealing a potentially critical difference in the pathogenesis of H5N1 infections. These results together show that infection with HP influenza viruses such as H5N1 and the 1918 pandemic virus leads to a rapid cell recruitment of macrophages and neutrophils into the lungs, suggesting that these cells play a role in acute lung inflammation associated with HP influenza virus infection. In addition, primary macrophages and dendritic cells were also susceptible to 1918 and H5N1 influenza virus infection in vitro and in infected mouse lung tissue.

Related:

• The Biology of Influenza
• Cellular Proteins in Influenza Virus Particles
• Influenza vaccines from plants

ENGAGE in research is an interactive resource for bioscience students.

The site has been designed to help science undergraduate students with advice and assistance on the most important aspects of scientific research. Whether you’re interested in research in general and want more information, or you’re struggling with statistical analyses, you’ll find the information there. You’ll also find worked examples, exercises with answers, help sheets and quick quizzes to help you test your understanding:

• Getting Started in Science
  Reviewing Literature
  Planning Your Research
  Step-by-Step Statistics
  Writing Scientifically
  Presenting Science
  Going Professional
  How Do I … ?

And it’s all free.

Related:

• Bioscience Horizons

In the ten years since its initiation, the international effort to eliminate lymphatic filariasis (LF) has made a large impact towards ridding the world of one of its most debilitating diseases. A new analysis finds that the LF elimination programme has prevented 6.6 million children from acquiring LF and stopped another 9.5 million people already infected with the disease from progressing to more debilitating stages. These efforts are the result of the most rapid scale-up of a drug administration programme in public health history, delivering what the study calls a “best buy in public health”. The paper assesses the impact of the World Health Organization-sponsored Global Programme to Eliminate Lymphatic Filariasis. These data illustrate that with the right partnerships, it is possible to make an extraordinary impact on the health of hundreds of millions of people at minimal cost. Workers are on track to accomplish our goal of elimination by 2020. When they do, this programme will be a leading case study for how to scale up disease elimination programmes globally.

Lymphatic filariasis, often called elephantiasis, is a parasitic infection spread by mosquitoes that causes grotesque, painful swelling of the limbs, breasts, and genitals. Considered a neglected tropical disease, LF almost exclusively affects the world’s poorest people. Approximately one-fifth of the world’s population (1.3 billion people) is at risk of contracting LF, and approximately 120 million people in 83 countries are currently infected. The Global Programme to Eliminate LF has already become the most rapidly scaled-up drug administration programme in public health history, and is on track to becoming the largest such programme in history. The new study found that since drug administrations began in 2000, the programme has administered more than 1.9 billion treatments to over 570 million people in 48 of the 83 countries with endemic LF. The LF elimination treatment programme utilises a combination of two anti-parasitic drugs, administered once yearly to everyone in an at-risk area. When given for a minimum of five consecutive years, these drugs have proven to effectively stop transmission of LF. The drugs used to eliminate LF are the same medications used to treat a number of intestinal worms and parasitic skin diseases, which infect hundreds of millions of people in developing countries and are major contributors to malnutrition, disability, delayed development, and problems during pregnancy.

The benefits of this programme go far beyond simply preventing LF infections. Because of the LF programme, at least 56.6 million children and 44.5 million women of childbearing age have been treated for intestinal worms, most multiple times. The drugs have also treated millions more in Africa for skin diseases. These data confirm what some public health officials have long asserted: that the LF programme is a “best buy” in public health, providing benefits that far outweigh its costs. The total cost per patient over the first eight years of the programme is estimated to be less than US $0.50. This low cost is made possible in part by the donation of albendazole and Mectizan from the programme’s two key pharmaceutical partners, GlaxoSmithKline and Merck & Co., Inc. The cost-efficiency combined with the programme’s achievements has prompted officials to call for the development of a dedicated fund for the treatment and elimination of other neglected tropical diseases. Future public-private partnerships will look to the global LF elimination effort as a standout example of how groups can come together to solve a major public health issue. We must take the lessons we have learned from the LF model and apply them toward the treatment and elimination of other neglected tropical diseases.

The Global Programme to Eliminate Lymphatic Filariasis: Health Impact after 8 Years. 2008 PLoS Negl Trop Dis 2(10): e317
In its first 8 years, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) achieved an unprecedentedly rapid scale-up. 1.9 billion treatments with anti-filarial drugs (albendazole, ivermectin, and diethylcarbamazine) were provided via yearly mass drug administration (MDA) to a minimum of 570 million individuals living in 48 of the 83 initially identified LF-endemic countries. To assess the health impact that this massive global effort has had, we analyzed the benefits accrued first from preventing or stopping the progression of LF disease, and then from the broader anti-parasite effects (‘beyond-LF’ benefits) attributable to the use of albendazole and ivermectin. Projections were based on demographic and disease prevalence data from publications of the Population Reference Bureau, The World Bank, and the World Health Organization. Between 2000 and 2007, the GPELF prevented LF disease in an estimated 6.6 million newborns who would otherwise have acquired LF, thus averting in their lifetimes nearly 1.4 million cases of hydrocele, 800,000 cases of lymphedema and 4.4 million cases of subclinical disease. Similarly, 9.5 million individuals - previously infected but without overt manifestations of disease - were protected from developing hydrocele (6.0 million) or lymphedema (3.5 million). These LF-related benefits, by themselves, translate into 32 million DALYs (Disability Adjusted Life Years) averted. Ancillary, ‘beyond-LF’ benefits from the 1.9 billion treatments delivered by the GPELF were also enormous, especially because of the 310 million treatments to the children and women of childbearing age who received albendazole with/without ivermectin (effectively treating intestinal helminths, onchocerciasis, lice, scabies, and other conditions). These benefits can be described but remain difficult to quantify, largely because of the poorly defined epidemiology of these latter infections. The GPELF has earlier been described as a best buy in global health; this present tally of attributable health benefits from its first 8 years strengthens this notion considerably.

Related:

• Neglected Tropical Diseases in Latin America and the Caribbean
• Elephantiasis video

BBC News

Ale, fermented using the yeast Saccharomyces cerevisiae, has been brewed since ancient times, possibly as early as 6000 BC. In contrast, lager beer, with its hallmark low-temperature fermentation (5°C–14°C), is a more recently developed alcoholic beverage, arising in Bavaria near the end of the Middle Ages. Lager gained worldwide popularity from the late 1800s with the advent of refrigeration, which allowed the necessary cool fermentation temperatures year-round. The lager yeast, Saccharomyces pastorianus, is distinct from S. cerevisiae in both physiological and genetic characteristics and is thought to have arisen in response to selective pressures from cold brewing temperatures. This selection may have taken place during successive rounds of cold-temperature fermentations resulting from a 16th century Bavarian law that prohibited brewing during summer months because of the inferior quality of summer-brewed beers. S. pastorianus has been shown to be a hybrid organism, and it is likely that lager yeast arose by “instantaneous speciation” due to an interspecific hybridization event between Saccharomyces cerevisiae and Saccharomyces bayanus that occurred during these selective growth conditions.

By examining the genome of S. pastorianus, a recently-published paper shows that the hybridization between yeast species which gave rise to lager yeasts happened independently at least twice, not once as previously thought, giving rise to two broad families of lager beer, Group 1 yeasts used to brew “Saaz”-type beers such as Pilsner and Budweiser, and Group 2 yeasts used to brew “Frohberg” lagers such as Orangeboom and Heineken. Both groups contain multiple copies of genes beneficial to brewing, such as those that ferment maltose. Likewise, genes that adversely affect the process have been lost.

This work paves the way for characterization of specific genetic features of each strain that could aid in the brewing process, and could lead to new insights on how to directly control flavor and aroma in beer.

Subscribe to podcasts (free):
[iTunes] Enhanced podcasts & videos
[RSS] mp3 podcasts (audio only)
Play this episode: Enhanced version
Audio only:

Reconstruction of the genome origins and evolution of the hybrid lager yeast Saccharomyces pastorianus. Genome Research, September 11, 2008
Inter-specific hybridization leading to abrupt speciation is a well-known, common mechanism in angiosperm evolution; only recently, however, have similar hybridization and speciation mechanisms been documented to occur frequently among the closely related group of sensu stricto Saccharomyces yeasts. The economically important lager beer yeast Saccharomyces pastorianus is such a hybrid, formed by the union of Saccharomyces cerevisiae and Saccharomyces bayanus-related yeasts; efforts to understand its complex genome, searching for both biological and brewing-related insights, have been underway since its hybrid nature was first discovered. It had been generally thought that a single hybridization event resulted in a unique S. pastorianus species, but it has been recently postulated that there have been two or more hybridization events. Here, we show that there may have been two independent origins of S. pastorianus strains, and that each independent group - defined by characteristic genome rearrangements, copy number variations, ploidy differences, and DNA sequence polymorphisms - is correlated with specific breweries and/or geographic locations. Finally, by reconstructing common ancestral genomes via array-CGH data analysis and by comparing representative DNA sequences of the S. pastorianus strains with those of many different S. cerevisiae isolates, we have determined that the most likely S. cerevisiae ancestral parent for each of the independent S. pastorianus groups was an ale yeast, with different, but closely related ale strains contributing to each group’s parentage.

Related:

• Brewing Beer
• In Praise of Yeast

Epstein-Barr virus (EBV) infects most people worldwide and is associated with several types of cancer due to its ability to induce cell proliferation. Only one virus protein, EBNA1, is expressed in all forms of EBV-associated tumors. New research investigated whether EBNA1 directly contributes to the development of nasopharyngeal carcinoma (NPC), the most common EBV-associated tumor. The researchers have shown that the EBNA1 protein of Epstein-Barr virus (EBV) disrupts structures in the nucleus of NPC cells, interfering with cellular processes that normally prevent cancer development.

The new study describes a novel mechanism by which virus proteins contribute to carcinogenesis. EBV is a common herpesvirus whose latent infection is strongly associated with several types of cancer including NPC, a tumor that is endemic in several parts of the world. With NPC only a few EBV proteins are expressed, including EBNA1. EBNA1 is required for the persistence of the EBV genomes, however, whether or not EBNA1 directly contributes to the development of tumors has not been clear, until now.

This study examined PML nuclear bodies and proteins in EBV-positive and EBV-negative NPC cells. Manipulation of EBNA1 levels in each cell type clearly showed that EBNA1 expression induces the loss of PML proteins and PML nuclear bodies through an association of EBNA1 with the PML bodies. PML nuclear bodies are known to have tumor-suppressive effects due to their roles in regulating DNA repair and programmed cell death, and accordingly, EBNA1 was shown to interfere with these processes. The researchers conclude that there is an important role for EBNA1 in the development of NPC, in which EBNA1-mediated disruption of PML nuclear bodies promotes the survival of cells with DNA damage. Since EBNA1 is expressed in all EBV-associated tumors, including B-cell lymphomas and gastric carcinoma, these findings raise the possibility that EBNA1 could play a similar role in the development of these cancers. The cellular effects of EBNA1 in other EBV-induced cancers will require further investigation.

Epstein-Barr Nuclear Antigen 1 Contributes to Nasopharyngeal Carcinoma through Disruption of PML Nuclear Bodies. 2008 PLoS Pathog 4(10): e1000170
Latent Epstein-Barr virus (EBV) infection is strongly associated with several cancers, including nasopharyngeal carcinoma (NPC), a tumor that is endemic in several parts of the world. We have investigated the molecular basis for how EBV latent infection promotes the development of NPC. We show that the viral EBNA1 protein, previously known to be required to maintain the EBV episomes, also causes the disruption of the cellular PML (promyelocytic leukemia) nuclear bodies (or ND10s). This disruption occurs both in the context of a native latent infection and when exogenously expressed in EBV-negative NPC cells and involves loss of the PML proteins. We also show that EBNA1 is partially localized to PML nuclear bodies in NPC cells and interacts with a specific PML isoform. PML disruption by EBNA1 requires binding to the cellular ubiquitin specific protease, USP7 or HAUSP, but is independent of p53. We further observed that p53 activation, DNA repair and apoptosis, all of which depend on PML nuclear bodies, were impaired by EBNA1 expression and that cells expressing EBNA1 were more likely to survive after induction of DNA damage. The results point to an important role for EBNA1 in the development of NPC, in which EBNA1-mediated disruption of PML nuclear bodies promotes the survival of cells with DNA damage.

Related:

• Viruses and Human Cancer
• Herpesvirus proteins that target key cellular processes
• Herpesviruses - not all bad?

Today is the official launch of our Small Worlds project at the University of Leicester. To celebrate, we have opened the Small Worlds wiki and would like to invite everyone to join.

Many early career stage laboratory researchers work in professional isolation, either in small research groups, or part time. The widespread availability of computers means that everyone is in constant contact with everyone else. However, this creates a false impression and the reality is that many junior scientists do not come into daily contact with their scientific peers. For these individuals, the opportunities offered by new technologies could be particularly important for career development.

Although Small Worlds is aimed at laboratory researchers, it is not limited to PhD students alone. We welcome technical staff and academics willing to assist with the professional development of new researchers. Likewise, although Small Worlds is centred on the University of Leicester, it is open to all irrespective of their location, because most of the problems faced by researchers are common to all. Small Worlds is an open initiative with a local flavour. We are able to offer this service by leveraging the power of free emerging web technologies.

Why do we need another site aimed at professional development of research staff? Unlike other initiatives such as Graduate Junction, Small Worlds is based on open tools loosely-joined and is outward-looking. These sites are not mutually exclusive - join both and see which suits you best.

So if you’re interested, please join the wiki and create a profile to share your professional online identities on the services (Twitter, delicious, Friendfeed, etc) we are using to build the project. We hope to talk to you soon.

RNA viruses such as poliovirus have high mutation rates, and a diverse virus population is required for full virulence. Most RNA viruses are highly error prone, and can use their replication infidelity to adapt to complex environments within an infected host. However, virus populations may experience bottlenecks, which limit their diversity and potentially reduce their virulence. Scientists have previously identified limitations on poliovirus spread after peripheral injection of mice expressing the human poliovirus receptor (PVR), and hypothesized that the host interferon response may contribute to the virus bottlenecks. They also suggested that natural barriers may limit the spread of RNA viruses within an infected host.

A recent paper examines poliovirus population bottlenecks in PVR mice and in PVR mice that lack the interferon α/β receptor, an important component of innate immunity. To monitor virus population dynamics, the researchers engineered a pool of marked polioviruses identifiable by a novel assay, infected susceptible mice by injection or oral inoculation, and determined the percentage of the marked viruses that successfully spread to various body sites, including the brain.

Following intramuscular or intraperitoneal injection of the marked-virus pool, a major bottleneck was observed during transit to the brain in PVR mice, but was absent in normal mice, suggesting that the interferon response was a determinant of the peripheral site-to-brain bottleneck. Since poliovirus infects humans by the fecal–oral route, we tested whether bottlenecks exist after oral inoculation of normal mice.

They found that, on average, only 10%–20% of the input viruses were found in most tissues, suggesting that barriers prevented the spread of the whole population. The importance of one such physical barrier, the colonic epithelium, was demonstrated in experiments where the colon was damaged prior to oral inoculation. Under these conditions, 30%–50% of the input viruses successfully spread to various body sites. Interestingly, two of the three major bottlenecks identified were partially overcome by pre-treating mice with dextran sulfate, which damages the colonic epithelium. Overall, they found that virus trafficking from the gut to other body sites, including the CNS, is a very dynamic, stochastic process. Multiple host barriers and the resulting limited poliovirus population diversity may help explain the rare occurrence of viral CNS invasion and paralytic poliomyelitis. These natural host barriers are likely to play a role in limiting the spread of many microbes.

Multiple Host Barriers Restrict Poliovirus Trafficking in Mice. 2008 PLoS Pathog 4(6): e1000082

Related:

• Imaging Poliovirus Entry in Live Cells
• Do viruses evolve to protect their hosts?
• Epidemics to eradication: the modern history of poliomyelitis

According to a new analysis, neglected tropical diseases (NTDs) as a group may have surpassed HIV/AIDS, tuberculosis and malaria as the most prevalent infectious diseases in Latin America and the Caribbean. The work found that NTDs are the most common infections of approximately 200 million of the poorest people in the region. They include tens of millions of cases of intestinal worm infections, and almost 10 million cases of Chagas disease, as well as schistosomiasis, trachoma, dengue fever, leishmaniasis, lymphatic filariasis (LF), and onchocerciasis. NTDs produce extreme poverty by adversely impacting child development, pregnancy outcomes and worker productivity. In some cases in Latin America and the Caribbean, NTDs also represent a living legacy of slavery, because they were first introduced into the region through the global slave trade, and even today they predominantly affect people of African descent and indigenous groups, as well as other vulnerable groups such as women and children.

In the coming years, schistosomiasis transmission could be eliminated in the Caribbean, and that transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America and the Caribbean with proven successful, cost effective and low-cost treatments. The most burdensome NTDs, such as Chagas disease, intestinal worm infections, and schistosomiasis may first require scale-up of existing resources and/or the development of new tools in order to achieve wider control and/or elimination. Ultimately, successful wide-scale efforts for NTD elimination will require an inter-sectoral approach that bridges public health with social services and environmental interventions.

Neglected diseases impose a huge burden on developing countries, constituting a serious obstacle for socioeconomic development and quality of life. They mostly affect people living either in shantytowns, indigenous communities or poor rural and agricultural areas. Last week, UK government officials announced that they will be contributing £50 million over the next five years toward the control and elimination of NTDs, including Guinea worm. In addition, the World Health Organziation announced that in 2007 alone, 546 million of the world’s poorest people received treatment for lymphatic filariasis at a cost of 10 cents per person, enabling them to live healthier more productive lives. After rainfall-induced disasters like Hurricane Ike, respiratory and intestinal infections usually increase and there is increased risk of breeding of the mosquito that transmits lymphatic filarisis in Haiti. While around three million people will be treated in Haiti in 2008 for lymphatic filariasis, additional resources are needed to step up and maintain treatment coverage in Haiti with its population of 9.5 million people, particularly in the wake of the Hurricane.

The Neglected Tropical Diseases of Latin America and the Caribbean: A Review of Disease Burden and Distribution and a Roadmap for Control and Elimination. 2008 PLoS Negl Trop Dis 2(9): e300

Related:

• Guinea Worm Disease
• Extreme Weather Events And Epidemics
• Novel application for an old drug: tamoxifen in the treatment of Leishmania infection
• Parasitic worm may increase susceptibility to AIDS virus