It took the entire world – people of all races, countries and religions – to eradicate smallpox. The final naturally occurring cases of “Variola major” in Bangladesh in 1978 and “Variola minor” in Somalia in 1977 marked the end to a chain of suffering and early death dating back to the Biblical plagues, and to Pharoah Ramses, who died from the very same disease. Since then we have continued to face countless pandemics – the Black Death, cholera, and now bird flu, SARS, HIV/AIDS and a new generation of zoonotic diseases – diseases that, often because of changes in population or climate, jump from animals to humans. We can’t be sure where the next smallpox will emerge, but we can be sure that it will take an effort larger than any single person or organization to defeat it.
Google’s Predict and Prevent initiative is working with partners to use digital, genomic and IT technology to identify “hot spots” of emerging threats and provide early warning before they become global crises. When you’re fighting a pandemic, early detection and early response can be the difference between dozens and hundreds of millions infected. What better birthday present could we offer the world after our 20th year, than to say we joined hands with a global movement and helped prevent the next smallpox?
Rapid ecological and social changes are increasing the risk of emerging threats, from infectious diseases to drought and other environmental disasters. This initiative will use information and technology to empower communities to predict and prevent emerging threats before they become local, regional, or global crises. Google.org’s initial focus will be on emerging infectious diseases, which are on the rise worldwide. Climate change, urbanization, and rising international travel and trade all contribute to this threat. Moreover, humans and animals are coming into closer contact because of environmental degradation and increased demand for animal products. Nearly three out of four new diseases in the last three decades have spread from animals to humans. While everyone faces increasing risk from emerging infectious diseases, the world’s poor – who have minimal or no access to health care and may live with and depend on animals for their livelihood – are exceptionally vulnerable and stand to suffer the most. This initiative supports two inter-related pathways from prediction to prevention. The first is vulnerability mapping and identification of “hot spots.” The second, creating systems to better detect threats to provide early warning and enable a rapid response.
HBV is a partially double-stranded DNA virus of the Hepadnaviridae family. The virus is carried in blood and in other body fluids including saliva, tears, semen and vaginal secretions and can be transmitted from person to person by a variety of means depending on the epidemiologic pattern within a geographic area.
Following acute infection with HBV, between 1 and 10% of healthy adults and 30–90% of infected babies become chronic virus carriers, some of whom are at risk of life-threatening diseases such as cirrhosis and primary hepatocellular carcinoma (HCC). Globally, at least 2 billion people or one third of the world population have been infected with HBV, over 378 million people (or 6% of the world population) are chronic carriers, and approximately 620,000 people die each year from acute and chronic HBV infection. In addition, approximately 4.5 million new HBV infections occur worldwide each year, of which a quarter progress to liver disease and cirrhosis.
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Vaccination is the most effective measure to control and prevent hepatitis B and its long-term serious consequences on global scale, both in terms of cost-effectiveness and benefit-cost ratios. The first available HBV vaccines were produced by harvesting the hepatitis B surface antigen (HBsAg) from plasma of chronic HBsAg carriers and became commercially available between 1981. Concern about the safety of these vaccines regarding transmission of blood-borne pathogens has proved to be largely unfounded. This led to the development of recombinant DNA hepatitis B vaccines, the second generation hepatitis B vaccines. The small envelope S protein is produced in yeast and the expressed HBsAg polypeptides then self-assemble into immunogenic spherical particles almost identical to the 22-nm particles found in serum of hepatitis B carriers. This new technology allowed the hepatitis B vaccine to become one of the most widely used vaccines in the world, in particular as part of the routine vaccination schedules for many of the world’s infants and children. During the 1990s, third-generation hepatitis B vaccines were developed in HBV transfected mammalian cells. These new HBV vaccines as well as novel new adjuvants have been shown to enhance the immunogenicity of such vaccines in immunocompromised hosts and non-responders to conventional vaccines.
Several hundred million doses of hepatitis B vaccine have been administered worldwide with an excellent record of safety and efficacy. Following a full course of vaccination (3 doses of vaccine given at 0, 1 and 6 months), seroprotection rates are close to 100% in children and almost 95% in healthy young adults. The results of effective implementation of universal hepatitis B vaccine programs are apparent in terms of reduction not only in incidence of acute hepatitis B infections, but also in the carrier rate in immunized cohorts, and in hepatitis-B-related mortality.
In accord with the WHO recommendations, universal HBV vaccination has been currently implemented in 168 countries world wide with an outstanding record of safety and efficacy. The effective implementation of such programmes of vaccination has resulted in a substantial decrease in disease burden, in the carrier rate and in hepatitis B-related morbidity and mortality. A future challenge is to overcome the social and economic hurdles which still hamper the introduction of HBV vaccination on a global scale.
Chemists have discovered that fungi can naturally absorb microscopic metal particles into their flesh in a way that could see metallic fungus used as catalysts or disinfectants. Industrial catalysts often rely on processes that happen on the surface of metals, so nanoparticles of catalyst with large surface-area-to-volume ratios are particularly effective. But such particles are only effective if they are prevented from clumping together using a chemical solution, which makes it difficult to separate the catalyst from the products of a reaction. Some fungi can assimilate and stabilise nanoparticles as they grow. Because the nanoparticles are immobilised on fungal filaments, they can be easily recovered later.
Fungal Templates for Noble-Metal Nanoparticles and Their Application in Catalysis. 2008 Angewandte Chemie International 47: 7876-7879
The combination of living structures with advanced materials, for example, as realized in cell-semiconductor coupling, or by using small biological forms as templates for nanotechnological applications, is becoming the focus of more and more interest. Composite materials consisting of magnetic or semiconducting nanoparticles incorporated into bacterial superstructures have been synthesized. To date, the main work on nanoparticle biomaterial hybrid structures has been done using functionalized gold nanoparticles assembled onto bacteria. For example Berry et al. were able to synthesize highly electrically conducting materials by assembling lysine-coated gold nanoparticles onto Bacillus cereus. It has also been demonstrated that cetyltrimetylammonium bromide (CTAB) terminated gold nanoparticles of different shapes (for example, nanorods) can be assembled onto the surface of bacteria. Other techniques for controlled assembly of gold nanoparticles were performed by DNA-modification of the surface, using diatoms and fungi as templates. Very recently Sugunan et al. reported the growth of fungi directly in gold nanoparticle solutions, using sodium glutamate as the reducing agent. Nutrition-driven assembly of gold onto the fungal mycelia was detected. The resulting hybrid structure exhibited optical properties of bulk gold and an electric resistivity close to that of the respective bulk solid.
In this article we show the ability of a variety of fungi to grow in citrate-stabilized colloidal medium and test their affinity for different noble-metal nanoparticles. Fungal growth takes place directly in the as-prepared gold, silver, platinum, and palladium nanoparticle solutions. Decoration of the fungal surface takes place without any further functionalization. The resulting hybrid systems have outer dimensions of about 0.1 cm3 and optical properties similar to the respective nanoparticle solutions. Differences in the metal affinities with respect to the morphology were observed by scanning electron microscopy. The specific surface area of the systems obtained has been assessed. A fungus-platinum hybrid system was shown to catalyze the redox reaction of hexacayanoferrate(III) and thiosulfate ions in aqueous solution. Dehydration of the metal-fungus hybrids was performed by critical point drying, thus conserving the three-dimensional macroscopic and microscopic shapes.
Besides the potential for applications in heterogeneous catalysis, other applications for these hybrid structures can also be considered. Silver or gold structures could be used as templates for surface-enhanced Raman spectroscopy and might also serve for fungi identification. Fungi decorated with silver could serve as disinfecting objects because of their high porosity and the well-known disinfection capability of silver. Besides electronic or sensoric applications, the effect described could be a useful tool for biochemical investigations, for example concerning the fungal heavy-metal-accumulation effect or for detecting differences in surface modifications (for example, between spores and hyphae).
Penicillins and synthetic beta-lactam antibiotics have dramatically transformed health care and quality of life in the 80 years since Alexander Fleming’s discovery of Penicillium. Large-scale production of beta-lactam antibiotics is the result of sustained industrial strain improvement, representing numerous rounds of mutagenesis and selection. Penicillin titers and productivities have increased by at least three orders of magnitude in the past 60 years, representing an unprecedented success in industrial strain improvement.
Current industrial Penicillium strains are derived from a single natural isolate of P. chrysogenum obtained during WWII from an infected cantaloupe. Biochemical and genetic analysis of industrial strains led to the identification of several important mutations in high-producing strains, including amplification of penicillin biosynthesis genes. However, much of the molecular basis for improved productivity remains to be elucidated. A detailed understanding of the molecular biology of P. chrysogenum is not only relevant for natural penicillins, but by applying genetic engineering approaches, it has become possible to extend the range of fermentation products to include beta-lactam derivatives that could previously only be produced by chemical modification.
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To gain more insight into penicillin synthesis, researchers have recently sequenced the 32.19 Mbp genome of P. chrysogenum and identified numerous genes responsible for key steps in penicillin production (Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum. Nature Biotechnology, 28 September 2008). DNA microarrays were used to compare the transcriptomes of the sequenced strain and a penicillinG high-producing strain. Transcription of genes involved in biosynthesis of valine, cysteine and alpha-aminoadipic acid – precursors for penicillin biosynthesis – as well as of genes encoding microbody proteins, was increased in the high-producing strain. Some gene products were shown to directly control beta-lactam output. Many key cellular transport processes involving penicillins and intermediates still remain to be characterized at the molecular level. Genes predicted to encode transporters were strongly overrepresented among the genes transcriptionally upregulated under conditions that stimulate penicillinG production, illustrating potential for future genomics-driven metabolic engineering.
Access to the full range of genomics techniques will be invaluable for further innovation in antibiotics production. Despite the massive improvements already achieved in classical strain improvement, further improvement of penicillin production remains a distinct possibility.
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:
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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.
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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.
Bioremediation is a process which uses microorganisms or their enzymes to return the natural environment altered by contaminants to its original condition.
Researchers at Johns Hopkins University have characterized a virus that is infectious to Anopheles gambiae – the mosquito primarily responsible for transmitting malaria. According to the researchers, this virus could potentially be used to pass on new genetic information to A. gambiae mosquitoes to help control malaria, which kills over one million people worldwide each year.
Paratransgenesis, the genetic manipulation of mosquito symbiotic microorganisms, is being considered as a potential strategy to control malaria. Microorganisms associated with Anopheles mosquitoes could be manipulated to alter the mosquito’s ability to become infected with and transmit the malaria parasites, or reduce mosquito fecundity or lifespan. The researchers identified the first potential microorganism (A. gambiae densovirus; AgDNV) for paratransgenesis of the major malaria vector Anopheles gambiae. AgDNV is highly infectious to A. gambiae larvae, disseminates to adult tissues and is transmitted vertically to subsequent generations. Recombinant AgDNV was able to transduce expression of an exogenous gene (EGFP) in A. gambiae cells and mosquitoes. EGFP-transducing virions infected mosquitoes, expressed EGFP in epidemiologically relevant tissues and were transmitted to offspring in a similar manner to wild-type virus. AgDNV could be used as part of a paratransgenic malaria control strategy by transduction of anti-Plasmodium genes or insect-specific toxins in Anopheles mosquitoes, as well as an easy-to-use system for transient gene expression and RNAi for basic laboratory research.
AgDNV is a member of the Parvovirus family, a “densovirus”, which are quite common in mosquitoes and other insects, but do not infect vertebrates such as humans. Although AgDNV does not appear to harm the mosquitoes, the researchers determined it is highly infectious to mosquito larvae and is easily passed on to the adults. The discovery came about serendipitously while the research team was conducting experiments to determine whether Wolbachia bacteria could be used to infect A. gambiae mosquito cells. During the analysis, they noticed an “artifact” that appeared as an unexpected prominent band in the gel used to detect the bacteria. The virus could be altered to kill the mosquito or make A. gambiae incapable of transmitting malaria. To test the concept, the research team successfully used altered AgDNV to express harmless green fluorescent protein in the adult mosquitoes which could be easily spotted under the microscope. In theory, we could use this virus to produce a lethal toxin in the mosquito or instruct the mosquito to die after 10 days, which is before it can transmit the malaria parasite to humans. However, these concepts are still many years away from practical use.
Methanogens may be among the most ancient forms of life and the methane they produce is a serious greenhouse gas. In this article in Microbiology Today, Setareh and James Chong explain how biological methane has the potential to be a carbon-neutral form of energy.
Methanogens are the main source of biological methane on the planet, producing in the order of a billion tonnes per annum globally. Methane is a serious greenhouse gas with 23 times the global warming potential (GWP) of CO2 over 100 years. That is, a single molecule of methane released into the atmosphere has the same thermal retention capacity as 23 molecules of CO2 over 100 years. The warming effect of methane is even worse over a shorter time scale – it has a GWP of 68 over 20 years – but it is a relatively unstable molecule once in the upper atmosphere. Contemplating the numbers is a rather frightening prospect: if all the methane produced by methanogens each year reached the atmosphere, it would be the equivalent of releasing 23 billion tonnes of CO2. Current global CO2 emissions are about 8 billion tonnes per year; thus, methanogens have the potential to provide three times the heating effect of anthropogenic carbon emissions! Fortunately, a large proportion of methanogen-produced methane is captured by other, methanotrophic, bacteria that can in turn use methane as an energy source.
It took the entire world – people of all races, countries and religions – to eradicate smallpox. The final naturally occurring cases of “Variola major” in Bangladesh in 1978 and “Variola minor” in Somalia in 1977 marked the end to a chain of suffering and early death dating back to the Biblical plagues, and to Pharoah Ramses, who died from the very same disease. Since then we have continued to face countless pandemics – the Black Death, cholera, and now bird flu, SARS, HIV/AIDS and a new generation of zoonotic diseases – diseases that, often because of changes in population or climate, jump from animals to humans. We can’t be sure where the next smallpox will emerge, but we can be sure that it will take an effort larger than any single person or organization to defeat it.
