Scientists Set 'Five Grand Challenges' For Nanotechnology Risk Research

Fourteen top international scientists in the field of nanotechnology have identified Five Grand Challenges for nanotechnology risk research that must be met if the technology is to reach its full potential. Their findings are the subject of a major paper published in the November 16th issue of the journal Nature.



The paper's lead author is Project on Emerging Nanotechnologies Chief Science Advisor Andrew Maynard. Co-authors (list attached) are among the world's foremost nanotechnology risk and applications researchers from universities, government, and industry in the United States and Europe.



Three of the paper's authors--Dr. Maynard, Dr. Martin A. Philbert of the University of Michigan School of Public Health, and Dr. Sally Tinkle of the National Institute of Environmental Health Sciences--discussed their recommendations at a program and live webcast on Thursday, November 16th at 9:00 a.m. in the 5th Floor Conference Room of the Woodrow Wilson International Center for Scholars (wilsoncenter/directions).



Dr. Maynard formerly served at the National Institute of Occupational Safety and Health (NIOSH), part of the U.S. Centers for Disease Control and Prevention (CDC), where he was instrumental in developing NIOSH's nanotechnology research program. He also was a member of the U.S. government's Nanoscale Science, Engineering and Technology (NSET) subcommittee of the National Science and Technology Council, and co-chaired the Nanotechnology Health and Environmental Implications (NEHI) working group of NSET.



Dr. Philbert is professor of toxicology and senior associate dean for research, School of Public Health, University of Michigan (Ann Arbor). His research includes the development of nanotechnology for intracellular measurement of biochemicals and ions, and for the early detection of brain tumors.



Dr. Tinkle is assistant to the deputy director at the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). She developed the NIEHS extramural nanotoxicology portfolio, chairs the NIH Nano Task Force Health Implications working group, and participates in the NSET and NEHI.







What: Scientists Set Five Grand Challenges for Nanotechnology Risk Research



Who: Dr. Andrew Maynard, Chief Science Advisor, Project on Emerging Nanotechnologies, Woodrow Wilson Center


Dr. Martin A. Philbert, Professor of Toxicology and Senior Associate Dean for Research, University of Michigan School of Public Health


Dr. Sally S. Tinkle, Assistant to the Deputy Director, National Institute of Environmental Health Sciences, National Institutes of Health


David Rejeski, Director, Project on Emerging Nanotechnologies



When: Thursday, November 16th, 2006, 9:00 - 10:00 a.m.
















Where: Woodrow Wilson International Center for Scholars, 5th Floor Conference Room. 1300 Pennsylvania Avenue, NW, Washington, DC



The Project on Emerging Nanotechnologies was launched in 2005 by the Woodrow Wilson International Center for Scholars and The Pew Charitable Trusts. It is dedicated to helping business, governments, and the public anticipate and manage the possible health and environmental implications of nanotechnology.



List of Paper's Authors and Institutions*



Dr. Andrew D. Maynard

Chief Science Advisor, Project on Emerging Nanotechnologies

Woodrow Wilson International Center for Scholars

Washington, DC, USA



Dr. Robert J. Aitken FiON

Director of Strategic Consulting

Nanotechnology Programme Director

Institute of Occupational Medicine (IOM)

Edinburgh, UK



Professor Dr. Tilman Butz

Nuclear Solid State Physics

University of Leipzig

Leipzig, GERMANY



Prof. Vicki Colvin

Executive Director, Center for Biological and Environmental Nanotechnology

Rice University

Houston, TX, USA



Prof. Ken Donaldson

Professor of Respiratory Toxicology

MRC/University of Edinburgh Centre for Inflammation Research

ELEGI Colt Laboratory

Queen's Medical Research Institute

Edinburgh, UK



Prof. Gunter Oberdorster

University of Rochester

Environmental Medicine

Rochester, NY, USA



Prof. Martin A. Philbert

Professor of Toxicology - Senior Associate Dean for Research

University of Michigan School of Public Health

Ann Arbor, MI, USA



Prof. John Ryan

Director, Bionanotechnology Interdisciplinary Research Centre

University of Oxford

Oxford, UK



Prof. Anthony Seaton CBE FMedSci

Emeritus Professor, Aberdeen University

Hon Senior Consultant, Institute of Occupational Medicine

Edinburgh, UK



Prof. Vicki Stonev
Napier University

Edinburgh, UK



Dr. Sally S. Tinkle

Office of the Deputy Director

National Institute of Environmental Health Sciences (NIEHS)

National Institutes of Health

Research Triangle Park, NC, USA



Dr. Lang Tran

Senior Scientist

Institute of Occupational Medicine (IOM)

Edinburgh, UK



Dr. Nigel J. Walker

Environmental Toxicology Program

National Institute of Environmental Health Sciences (NIEHS)

National Institutes of Health

Research Triangle Park, NC, USA



Dr. David B. Warheit

Research Fellow

DuPont Haskell Laboratory for Health and Environmental Sciences

Newark, DE, USA



*Opinions and views expressed in the article are of those of the authors. Institutions are listed for identification purposes only.


Contact: Sharon McCarter


Project on Emerging Nanotechnologies

Porous Walled Hollow Glass Microspheres Have Applications In Energy, Medicine, Other Fields

A licensing agreement between the U.S. Department of Energy's Savannah River National Laboratory (SRNL) and specialty glass provider Mo-Sci Corporation will make SRNL's unique Porous Walled Hollow Glass Microspheres available for use in targeted drug delivery, hydrogen storage and other uses, including applications still being developed.



Hollow glass microspheres have been used for years in light-weight filler material, insulation, abrasives and other uses. What makes SRNL's patent-pending microspheres unique is the network of interconnected pores in the microsphere walls, which allow the tiny "microballoons" to be filled with, hold, and release gases and other materials. Each porous walled hollow glass microsphere is about 50 microns in diameter, about half the width of a human hair. Its walls, which are about 10,000 angstroms thick (an angstrom is one-tenth of one-billionth of a meter) feature pores that range from 100 to 300 angstroms, which allow gases to enter the tiny spheres and be stored or cycled on absorbents inside.



SRNL originally developed the unique microspheres as a solid-state storage method for hydrogen; they have been successfully demonstrated to store and release the gas.



Work since then has shown potential in other uses, including battery applications and medicine. An article by authors from the Medical College of Georgia and SRNL, which has been accepted for publication in the peer-reviewed journal Nanomedicine: Nanotechnology, Biology and Medicine, discusses a possible application for the delivery of anti-cancer drugs. (Porous-wall hollow glass microspheres as novel potential nanocarriers for biomedical applications; Shuyi Li, Lynsa Nguyen, Hairong Xiong, Meiyao Wang, Tom C.-C. Hu, Jin-Xiong She, Steven M. Serkiz, George G. Wicks, William S. Dynan; article in press)



Under the license agreement, Mo-Sci will provide SRNL with a cost-effective supply of the microspheres to continue research and development of additional applications. It also provides for aggressive marketing by Mo-Sci to be the premier supplier for medical R&D applications.



Source: Angeline French


DOE/Savannah River National Laboratory

Intestinal Cells Surprisingly Active In Pursuit Of Nutrition And Defense

Every cell lining the small intestine bristles with thousands of tightly packed microvilli that project into the gut lumen, forming a brush border that absorbs nutrients and protects the body from intestinal bacteria. In the June 29, 2009 issue of the Journal of Cell Biology, Matthew McConnell, Matthew Tyska, and colleagues now find that microvilli extend their functional reach even further using a molecular motor to send vesicles packed with gut enzymes out into the lumen to get a head start on breaking down their substrates.



Microvilli have traditionally been viewed as passive scaffolds that increase the surface area of the gut wall. The apical plasma membrane tightly wraps around each protrusive bundle of actin, providing more space for nutrient processing and absorption. The motor protein myosin-1a (myo1a) maintains this structure by connecting the plasma membrane to the actin filaments.



In 2007, Tyska and colleagues found that myo1a functions in isolated brush borders to actively move membrane along the length of the microvilli, like a "membrane escalator." To their surprise, at the top of these escalators - the tips of the microvilli - the membrane pinched off to form small vesicles that were released into the surrounding medium. According to Tyska, when they showed their data to gastroenterologists, they immediately asked "Why would brush borders do that? They're wasting perfectly good apical membrane!" Tyska therefore wanted to see if vesicle shedding was a bona fide physiological function for microvilli.



Sure enough, scanning electron micrographs of rat intestines showed protrusions at the tips of microvilli that looked similar to budding vesicles. And a look at the gut's contents revealed vesicles enriched in the brush border enzyme intestinal alkaline phosphatase (IAP). The vesicles were packed with classical brush border membrane proteins such as aminopeptidases and sugar-processing enzymes, suggesting that the vesicles were derived from microvilli. The vesicles also contained several proteins such as annexin A13 that bend cell membranes and could form part of the vesicle budding machinery.



One protein definitely involved in vesicle formation is myo1a. Myo1a knockout mice still produce lumenal vesicles but they are irregularly sized and no longer enriched in specific proteins like IAP. Tyska thinks that these knockout vesicles are actually chunks of microvillar membrane that are nonspecifically shed when myo1a isn't present to keep them attached to the actin core.



Returning to the gastroenterologists' question: Why would brush borders do that? McConnell et al. showed that the packaged enzymes were exposed on the vesicles' outer surface and were catalytically active. Releasing the enzymes in vesicles might increase their mixing with substrates in the gut's contents. Tyska is particularly interested in IAP, which has recently been shown to detoxify the bacterial outer-membrane component lipopolysaccharide. Releasing IAP in lumenal vesicles could be an important defense mechanism against intestinal pathogens.



McConnell, R.E., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200902147.



Source:
Rita Sullivan


Rockefeller University Press

Cross-Species Strategy Might Be A Powerful Tool For Studying Human Disease

A new study takes advantage of genetic similarities between mammals and fruit flies by coupling a complex genetic screening technique in humans with functional validation of the results in flies. The new strategy, published by Cell Press in The American Journal of Human Genetics, has the potential to be an effective approach for unraveling genetically complex human disorders and providing valuable insights into human disease.



Genome-wide association studies (GWASs) involve sifting through the complete set of DNA from many individuals to identify genetic variations associated with a particular disease. Although this technique has proven to be a powerful tool for developing a better understanding of diseases, such as Alzheimer's disease (AD), that involve multiple genetic variations, there are substantial limitations. Perhaps most significantly, follow-up studies aimed at validating disease-associated genetic variations in humans require large sample sizes and a great deal of effort. The current study validates GWAS results by using an inventive alternative approach.



"Simple genetic models of human disease, such as in the fruit fly, have been important experimental tools for many years, particularly for large-scale functional testing of genes," explains a senior study author, Mel B. Feany, MD, PhD, from Brigham and Women's Hospital.. "We therefore hypothesized that the fly disease model might fulfill the growing need for efficient strategies for validation of association signals identified by GWAS."



Dr. Joshua M. Shulman and colleagues implemented a two-stage strategy to enhance a GWAS of AD neuropathology by integrating the results of gene discovery in humans with functional screening in a fly model system relevant to AD biology. Specifically, the researchers evaluated 19 genes from 15 distinct genomic regions identified in a human GWAS designed to identify genes that influence AD pathology. In six out of these 15 genomic regions, a causal gene was subsequently identified in the fly disease model on the basis of interactions with the neurotoxicity of Tau protein, a well-known constituent of AD pathology.



The authors also discuss the potential for application of their technique to studies examining other human diseases. "Evidence is emerging in support of a polygenic model of inheritance for complex genetic disorders, particularly neuropsychiatric diseases, in which hundreds or even thousands of common gene variants collectively contribute to disease risk," says co-author Philip L. De Jager, MD, PhD, also of Brigham and Women's Hospital. "Our strategy of coupling human GWAS with functional genetic screening in a model organism will likely be a powerful strategy for follow-up of such signals in the future in order to prioritize genes and pathways for further investigation."



Source:

Elisabeth Lyons

Cell Press

A Fungus To Blunt Mosquitoes' Sense Of Smell

Sick people often lose their sense of smell and their appetite. If this happened to mosquitoes, they would not be able to feed on humans and spread malaria. A team of Penn State entomologists is looking for an insect disease that will infect mosquitoes and impair their sense of smell.



Supported by a recent $100,000 grant from the Bill and Melinda Gates Foundation's Grand Challenges Explorations Initiative, the researchers were among 81 projects funded from more than 3,000 applications in the second round of the program. Grand Challenges focuses on novel approaches to prevent and treat infectious diseases, such as HIV, malaria, tuberculosis, pneumonia and diarrheal diseases.



The researchers, who include Thomas Baker and Matthew Thomas, professors of entomology and Andrew Read, professor of biology and entomology and Eberly College of Science distinguished senior scholar, are all part of Penn State's Centers for Chemical Ecology and for Infection Disease Dynamics. They plan to test a variety of naturally occurring insect pathogenic fungi.



"We will infect malaria mosquitoes with an insect-specific fungus to determine how much the infected mosquitoes' sense of smell is suppressed, thus reducing their ability to find human hosts and transmit malaria," said Thomas.



Mosquitoes transfer malaria parasites to humans when the female mosquitoes bite humans for blood meals to allow them to lay eggs. Male mosquitoes and non-reproducing females sip nectar or other sources of sugar for energy. Mosquitoes do not have noses, but smell using their antennae.



The researchers will infect batches of mosquitoes with a variety of fungi known to infect insects. They will expose the mosquitoes and an uninfected control group to potential mammalian blood meal -- an animal in an adjacent cage. Those mosquitoes that approach the warm-blooded food source will be separated out from those that are uninterested.



Once the researchers know the individual mosquito's behavior, they will investigate their olfactory receptor neurons to see if the fungus has impaired the mosquitoes' ability to smell. When the researchers identify fungi that will impair mosquito smelling ability, they will find ways to introduce the fungi into the environment so the mosquitoes can infect themselves.



"Our aim is to impregnate bed-nets or other things like eave curtains, hanging cloth or residual sprays in human dwellings with an insect infecting fungus like one already registered in Africa to control locusts and grasshoppers and infect malaria mosquitoes so that they no longer can smell and attack humans," the researchers said.



Source:
A'ndrea Elyse Messer


Penn State

First Whole Genome Sequencing Of Family Of Four Reveals New Genetic Power

The Institute for Systems Biology (ISB) has analyzed the first whole genome sequences of a human family of four. The findings of a project funded through a partnership between ISB and the University of Luxembourg was published online today by Science on its Science Express website. It demonstrates the benefit of sequencing entire families, including lowering error rates, identifying rare genetic variants and identifying disease-linked genes.


"We were very pleased and a little surprised at how much additional information can come from examining the full genomes of the same family." said David Galas, PhD, a corresponding author on the paper, an ISB faculty member and its senior vice president of strategic partnerships. "Comparing the sequences of unrelated individuals is useful, but for a family the results are more accurate. We can now see all the genetic variations, including rare ones, and can construct the inheritance of every piece of the chromosomes, which is critical to understanding the traits important to health and disease."


"The continuing decline in the difficulty and cost of sequencing now enables us to use these new strategies for deriving genetic information that was too difficult or expensive to access in the past," Galas said.


ISB partnered with Complete Genomics, based in Mountain View California, to sequence the genomes of a father, mother and two children. Both children had two recessive genetic disorders, Miller syndrome, a rare craniofacial disorder, and primary ciliary dyskinesia (PCD), a lung disease. By sequencing the entire family, including the parents, researchers were able to reduce the number of candidate genes associated with Miller syndrome to four.


"An important finding is that by determining the genome sequences of an entire family one can identify many DNA sequencing errors, and thus greatly increase the accuracy of the data," said Leroy Hood, MD, PhD, the paper's other corresponding author, and co-founder and president of ISB. "This will ultimately help us understand the role of genetic variations in the diagnosis, treatment, and prevention of disease."
An exciting finding from this study, the first direct estimate of human intergenerational mutation rate, is how much the genome changes from one human generation to the next - the intergenerational mutation rate. The researchers found that gene mutations from parent to child occurred at half the most widely expected rate.


"This estimate could have implications for how we think about genetic diversity, but more importantly the approach has the potential to increase enormously the power and impact of genetic research," said Galas. "Our study illustrates the beginning of a new era in which the analysis of a family's genome can aid in the diagnosis and treatment of individual family members. We could soon find that our family's genome sequence will become a normal part of our medical records."


Source

Institute for Systems Biology

Researchers Catch Ion Channels In Their Opening Act

Each thought or action sends a million electrical signals pulsing through your body. At the heart of the process of generating these electrical impulses is the ion channel.



A new study by researchers from the University of Illinois measures movements smaller than one-billionth of a meter in ion channels. This movement is critical to how these tiny pores in the cell membrane open and close in response to changes in voltage across the membrane. The findings appear this week in the journal Neuron.



Ion channels belong to a special class of proteins embedded in the oily membranes of the cell. They regulate the movement of charged particles, called ions, into and out of the cell. Much like water faucets that can be controlled by turning a knob, channels open or close in response to specific signals. For instance, ion channels that open in response to pressure on the skin regulate our sense of touch.



Voltage is an important switch that controls how some channels open. The voltage across the cell membrane depends on the balance of ions inside and outside the cell and also on the type of ions. Voltage-gated channels are critical for transmitting messages from the brain to different parts of the body by means of nerve cells.



"There has been a large controversy in the field with regards to how these channels respond to voltage," said University of Illinois physics professor Paul Selvin, who led the study. The controversy centers on a key segment of the ion channel called the voltage sensor.



The voltage sensor gauges the voltage across the membrane and instructs the channel to open or close.



One model for the movement of the voltage sensor suggests that it moves up and down by only a small amount, tugging on the pore of the ion channel and opening it just enough for ions to get through. In 2003, Roderick MacKinnon, who won a Nobel Prize in chemistry for his work on the X-ray crystal structures of ion channels, proposed a competing idea, the "paddle model." This idea involved a large movement of the voltage sensor across the membrane. X-ray crystal structures provide snapshots of proteins in exquisite detail, allowing researchers to look at the positions of every atom.



According to Selvin, a problem with the crystal structure is that it only offers a static snapshot of what the protein looks like and provides only limited information about how different parts of the protein move. Another concern is that the conditions used to obtain protein crystals sometimes alter the original structure of the protein.



In the new study, postdoctoral researcher David Posson worked with Selvin to put the models of voltage sensor movement to the test.



They studied the voltage sensor segment in a specific ion channel called the Shaker potassium channel. This protein was first discovered in fruit flies after researchers observed that a mutation in the channel caused the flies to vigorously shake.
















To preserve channels in their original state, Posson studied ion channels inserted into the membranes of frog eggs. He tested the two models using a fluorescence technique called Lanthanide resonance energy transfer (LRET) which allowed him to measure small movements in proteins. The technique involves the use of a special pair of molecular bulbs that glow either brightly or dimly depending on how far apart they are. The measurement is sensitive to movements as small as one-billionth of a meter. Posson also needed a way to control the voltage across the membrane.



He used an approach called electrophysiology that involves inserting electrodes into the frog egg. This gave him the ability to change the voltage across the membrane and regulate channel opening.



"Our approach brings together two distinct biophysical techniques, electrophysiology and fluorescence, which have been independently useful for the study of proteins," Posson said.



To map the movement of the voltage sensor during channel opening, Posson measured distances from several different vantage points on the protein.



"It's a lot like dispatching a team of molecular surveyors that stand at specific positions on the surface of a protein and collect distances from point A to point B," Posson said. "With enough measurements, the surveyors can build a map of the three dimensional shape of the protein." Posson discovered that the largest distances traversed by the sensor were about two to three times smaller than what was predicted by the paddle model. It showed that the sensor moves by only a small amount to allow the flow of ions.



"We are seeing a clear result that the movement of the sensor isn't super teeny, and isn't super huge," Posson said. The measurements challenge models that predicted large movements of the protein segments, such as the paddle model. The findings also refute models that have a near zero movement of the sensor region. "It's a small piece to the puzzle of how the voltage sensor moves" Selvin said.







Source: Kaushik Ragunathan


University of Illinois at Urbana-Champaign

The International Union For Pure And Applied Biophysics And Springer Will Collaborate On A New Journal Biophysical Reviews

The International Union for Pure and Applied Biophysics (IUPAB) and Springer will launch the journal Biophysical Reviews in spring 2009. Biophysical Reviews is the new official journal of the IUPAB, the leading international biophysics organization consisting of 52 national societies with approximately 15,000 members. The entire IUPAB Council will form the editorial board of the new journal in order to demonstrate the close affiliation between the Springer journal and the IUPAB.



Biophysical Reviews will publish short and critical reviews from key scientists active in the field. The quarterly journal will cover the entire field of biophysics, generally defined as the science of describing biological phenomena and resolving their underlying principles using the concepts and techniques of physics. This includes, but is not limited to, such areas as bioinformatics, biophysical methods and instrumentation, medical biophysics, biosystems and cell biophysics. The editor-in-chief, Professor Jean Garnier of the Institut National de la Recherche Agronomique (INRA) - UnitГ© MathГ©matique Informatique et GГ©nome (France) will work closely with the expert international editorial board.



Dr. Sabine Schwarz, Senior Editor for Life Sciences at Springer, said, "We are excited about the IUPAB's decision to cooperate with Springer. The new journal will provide top-level reviews in biophysics, which will of course all be peer-reviewed. This aspect, combined with the high-caliber editorial board and the IUPAB's previous publishing experience, provides the perfect preconditions for a successful journal."



Professor Kuniaki Nagayama, President of the International Union for Pure and Applied Biophysics, said, "The IUPAB requires a useful and broadly informative official journal, and our old journal did not serve our purposes well. Now, in cooperation with Springer, we are starting the new official journal, Biophysical Reviews. I am pleased to have the opportunity to be part of the development of this new journal, together with the IUPAB, biophysicists affiliated with the IUPAB and all others interested in biophysics."



Springer will publish Biophysical Reviews in both print and electronic formats. It will be available via springerlink, Springer's online information platform, and will include fast, electronic publication in Online First™, as well as Cross Reference Linking and Table of Content Alerts. All potential authors have the option, via the Springer Open Choice™ program, of publishing their articles using the open access publishing model.



The International Union for Pure and Applied Biophysics is a member of the International Council for Science family. Its function is to support research and teaching in biophysics.



Springer is the second-largest publisher of journals in the science, technology, and medicine (STM) sector and the largest publisher of STM books. It publishes on behalf of more than 300 academic associations and professional societies. Springer is part of Springer Science+Business Media, one of the world's leading suppliers of scientific and specialist literature. The group publishes over 1,700 journals and more than 5,500 new books a year, as well as the largest STM eBook Collection worldwide. Springer has operations in over 20 countries in Europe, the USA, and Asia, and some 5,000 employees.







Biophysical Reviews

ISSN: 1867-2450 (print version)

ISSN: 1867-2469 (electronic version)



Source: Renate Bayaz


Springer

The Eco-friendly Brain

Our brains, it turns out, are eco-friendly. A study published in Science and reviewed by F1000 Biology members Venkatesh Murthy and Jakob Sorensen reveals that our brains have the amazing ability to be energy efficient.



Brain cells generate and propagate nerve impulses, or action potentials, by controlling the flow of positive sodium and potassium ions in and out of the cells. Re-establishing the ion equilibrium after an action potential requires energy.



The amount of energy needed for action potentials was previously estimated using a giant nerve cell from squid. Now, researchers at the Max-Planck Institute for Brain Research in Germany show that squid cell studies overestimated the amount of energy necessary to generate an action potential by almost a factor of four, suggesting human brains have the same potential to be energy efficient.



The researchers used a novel technique to record the voltage generated by nerve cells to "show that a rather subtle separation between the timing of sodium entry and potassium exit during action potentials can determine how much energy is expended to maintain the ionic gradients," Murthy says.



Murthy goes on to say that "[these results] are important, not just for a basic understanding of brain metabolism, but also for interpreting signals detected by non-invasive brain imaging techniques." Sorensen concludes that "the amazing thing is that we didn't realize the result a long time ago!"



The full text of this article is available free for 90 days here.



An abstract for the paper, Energy-Efficient Action Potentials in Hippocampal Mossy Fibers by Alle, Roth and Geiger, is here.



Source:
Steve Pogonowski


Faculty of 1000: Biology and Medicine

TAU Researchers Look To Marine Sponges To Beat Resistance To Antibiotics

No matter how sophisticated modern medicine becomes, common ailments like fungal infections can outrun the best of the world's antibiotics. In people with compromised immune systems (like premature babies, AIDS victims or those undergoing chemotherapy for cancer) the risk is very high: contracting a fungal infection can be deadly.



Now Tel Aviv University zoologists are diving deep into the sea to collect unique chemicals - drugs of the future - to beat unnecessary death by fungal infection. And their secret weapon is the common marine sponge.



Prof. Micha Ilan from the Department of Zoology at TAU, who is heading the project, has already identified several alternative antibiotic candidates among the unique compounds that help a sponge fend off predators and infections. He and his graduate students are now identifying, isolating and purifying those that could be the super-antibiotics of the future.



The research group at TAU has found and isolated thousands bacteria and fungi, including a few hundred unique actinobacteria. So far, several tens hold promise as new drugs.



From the Sea to the Lab



"Resistance to antibiotics has become an unbelievably difficult challenge for the medical community," says Prof. Ilan. "Sponges are known for hosting an arsenal of compounds that could work to fight infections. We're now culturing huge amounts of microorganisms, such as actinobacteria, that live in symbiosis with marine sponges."



Marine sponges were recently made famous by the popular Nickelodeon TV cartoon SpongeBob SquarePants, which features a sea sponge who lives in a pineapple beneath the ocean. In real life, sea sponges are animals whose bodies consist of an outer thin layer of cells and an inner mass of cells and skeletal elements. The sedentary creatures don't really have the sort of adventurous life that the cartoon depicts.



Marine sponges can't move. Glued to the seafloor, they must rely on the flow of water through their bodies to collect food and to remove waste. This has led to a unique adaptive response to enemies and competition. Sponges don't have teeth, or shells, but protect themselves by building associations and partnerships with bacteria and fungi. Tel Aviv University is tapping into these relationships - looking at the same chemicals that the sponge uses for defense to fight infection in humans.



Research Combines Several Fields of Study



Drug developers have known for decades about the potential goldmine of pharmaceuticals in the marine environment, particularly among sedentary life like marine sponges.



"One of the major problems is that these novel and natural compounds are found in very small quantities," Prof. Ilan explains. Collecting and extracting such large amounts of these unique chemicals would require huge quantities of animals to be sacrificed, a practice which is not in line with zoological conservationist values. So Prof. Ilan takes cultures from sea sponges with minimal damage to the natural environment. He then grows their symbionts and tests them in a "wet" laboratory. The methods Prof. Ilan has perfected can now be used by other scientists developing pharmaceuticals from marine sponges.



"Our research is unique in that we take both an agricultural and microbiological approach - not found often in the drug discovery community," says Prof. Ilan, whose work is done in collaboration with the School of Chemistry's Prof. Yoel Kashman and Prof. Shmuel Carmeli.



Source: George Hunka


American Friends of Tel Aviv University

Study Advances Evidence For Receptor's Role In Alcohol Pleasure And Problems

A genetic variant of a receptor in the brain's reward circuitry heightens the stimulating effects of early exposures to alcohol and increases alcohol consumption, according to a new study by researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH). Conducted in rhesus monkeys, the study extends previous research that suggests an important role for a similar brain receptor variant in the development of human alcohol use disorders. A report of the findings is published in the March, 2007 issue of the Archives of General Psychiatry.



"Although the pathway to alcoholism is influenced by many factors, our findings affirm that individuals who possess this receptor variant may experience enhanced pleasurable effects from alcohol that could increase their risk for developing alcohol abuse and dependence," notes Markus Heilig, M.D., Ph.D., NIAAA Clinical Director and the study's senior author.



Molecules known as opioid peptides bind to opioid receptors in the brain to signal experiences of reward and reinforcement, as well as the euphoria and other positive subjective effects produced by alcohol. Previous studies have shown that, among the brain's various subtypes of opioid receptors, the mu-subtype is most likely responsible for transmitting alcohol's positive effects.



"We also know that there are several genetic variants of the human mu-opioid receptor," notes first author Christina Barr, V.M.D., Ph.D., a lead investigator in NIAAA's Laboratory of Clinical and Translational Studies and Laboratory of Neurogenetics. "One of these, designated 118G, has a greatly enhanced ability to bind opioid peptides. People who have this variant of the receptor have reported increased euphoria following alcohol consumption."



Drs. Barr, Heilig, and their colleagues note that recent studies have linked the 118G mu-opioid receptor with alcohol dependence in humans. In the current study, the researchers explored the link between genetic variants of mu-opioid receptors and alcohol-related behaviors in a group of 82 rhesus monkeys.



"A mu-opioid receptor variant that is functionally similar to the human 118G variant occurs in these animals," explained Dr. Barr. "That is, it also has a greatly enhanced ability to bind opioid peptides. We hypothesized that monkeys that had the gene for this receptor variant would experience enhanced alcohol stimulation and, therefore, consumption.



Groups of monkeys had access to both alcoholic and non-alcoholic solutions for one hour per day for a period of six weeks. Researchers measured the animals' alcohol intake and post-intake activity, and determined which monkeys carried the gene for the mu-opioid receptor similar to the human 118G receptor. Activity measures are commonly used in animal studies to assess alcohol's pleasurable effects. As predicted, the researchers found that monkeys with the variant gene showed increased activity following alcohol consumption. They also found that male animals with the variant had a clear preference for the alcohol solution and consumed on average almost twice as much alcohol as other animals. Males with the variant also became intoxicated on almost 30 percent of testing days, while other animals did so only on an average of 8 percent of testing days.
















"The male-restricted effect of this gene is interesting, and parallels other recent evidence that opioid transmission may play a greater role in alcohol problems among some males than among females," explained Dr. Heilig. This information also complements recent data suggesting that alcohol-dependent people with the gene for the 118G receptor have a better therapeutic response to medications that block opioid receptors. More broadly, the finding underscores the important role that the pleasurable and stimulating initial effects of alcohol play in the subsequent development of alcohol problems."






The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems and disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at niaaa.nih/. The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.



References:



Barr CS, Schwandt M, Lindell SG, Chen SA, Goldman D, Suomi SJ, Higley, JD, Heilig M. Association of a Functional Polymorphism in the Г¬-Opioid Receptor Gene With Alcohol Response and Consumption in Male Rhesus Macaques. Archives of General Psychiatry. 2007;64:369-376



Ray LA, Hutchison KE. A polymorphism of the mu-opioid receptor gene (OPRM1)
and sensitivity to the effects of alcohol in humans. Alcohol Clin Exp Res. 2004; 28:1789-1795.



Contact: John Bowersox


NIH/National Institute on Alcohol Abuse and Alcoholism

NCI-Penn Collaboration Finds Targeted Immune Cells Shrink Tumors In Mice

Researchers have generated altered immune cells that are able to shrink, and in some cases eradicate, large tumors in mice. The immune cells target mesothelin, a protein that is highly expressed, or translated in large amounts from the mesothelin gene, on the surface of several types of cancer cells. The approach, developed by researchers at the University of Pennsylvania School of Medicine and the National Cancer Institute (NCI), shows promise in the development of immunotherapies for certain tumors. The study appears online this week in the Proceedings of the National Academy of Sciences.



Expression of mesothelin is normally limited to the cells that make up the protective lining (mesothelium) of the body's cavities and internal organs. However, the protein is abundantly expressed by nearly all pancreatic cancers and mesotheliomas and by many ovarian and non-small-cell lung cancers. Although the biological function of mesothelin is not known for certain, it is thought to play a role in the growth and metastatic spread of the cancers that express it.



"Since tumor cells are derived from the body's normal cells, the immune system often does not recognize tumor molecules as dangerous or foreign and does not mount a strong attack against them," said Ira Pastan, M.D., chief of the Laboratory of Molecular Biology in NCI's Center for Cancer Research, a study collaborator. Moreover, even though it is possible to genetically engineer immune system cells to recognize molecules on tumor cells, most of the molecules found on tumor cells are also found on normal cells. But, Pastan notes, "Mesothelin is a promising candidate for generating tumor-targeting T cells, given its limited expression in normal tissues and high expression in several cancers."



Previous laboratory research has shown that certain immune system cells, called T cells, can kill tumor cells that express mesothelin. In addition, studies in both animals and humans have shown that antibodies directed against mesothelin protein can shrink tumors.



In the new study, the research team genetically engineered human T cells to target human mesothelin. To produce them, a modified virus was used as a delivery vehicle, or vector, to transfer synthetic genes to T cells. These genes directed the production of hybrid, or chimeric, proteins that can recognize and bind to mesothelin and consequently stimulate the proliferation and cell-killing activity of the T cells. In laboratory studies, the team found that the engineered T cells proliferated and secreted multiple cytokines when exposed to mesothelin. Cytokines are proteins that help control immune functions. The cells also expressed proteins that made them resistant to the toxic effects of tumors and their surrounding tissues.
















To study the effects of the engineered T cells on tumor tissue, the researchers implanted human mesothelioma cells underneath the skin of mice. About six weeks later, when tumors had formed and progressed to an advanced stage, the engineered T cells were administered to the mice. Direct injection of the T cells into tumors or into veins of the mice resulted in disappearance or shrinkage of the tumor.



"Based on the size of the tumors and the number of cells administered, we estimate that one mesothelin-targeted T cell was able to kill about 40 tumor cells," said study leader Carl H. June, M.D., Professor of Pathology and Laboratory Medicine and director of Translational Research at Penn's Abramson Cancer Center. "This finding indicates that small doses of these cells may have potential in treating patients with large tumors. Clinical trials are being developed to investigate this approach in patients with mesothelioma and ovarian cancer."







PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.



Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.



The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's top ten "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.



Source: Karen Kreeger


University of Pennsylvania School of Medicine

Synthetic Platelets Halve Clotting Time

Blood loss is a major cause of death from roadside bombs to freeway crashes. Traumatic injury, the leading cause of death for people age 4 to 44, often overwhelms the body's natural blood-clotting process.



In an effort to enhance the natural process, a team led by Erin Lavik, a new Case Western Reserve University biomedical engineering professor, and her former doctoral student, James P. Bertram, built synthetic platelets that show promise in halting internal and external bleeding.



Their work is published in Science Translational Medicine.



The researchers were inspired by studies showing there are few options to treat soldiers suffering from internal injuries in Afghanistan and Iraq. They wanted to develop a treatment medics can keep in their field packs.



"The military has been phenomenal at developing technology to halt bleeding, but the technology has been effective only on external or compressible injuries," Lavik said. "This could be a compliment to current therapies."



Blood platelets are the structural and chemical foundation of blood clotting, a complex cascade of events that works well with normal cuts and scrapes but can be overmatched by serious injury.



Using other's platelets can enhance clotting but carries risks of several complications. And these platelets must be refrigerated and have a short shelf life.



Bertram and Lavik developed platelets made from biodegradable polymers. The synthetic platelets are designed to home in and link up with natural platelets at the site of an injury.



In essence, adding artificial platelets to a traumatic injury site is akin to adding sand bags to a levy along a flooding river.



The natural platelets, activated by injury, emit chemicals that bind natural platelets and the additional synthetics into a larger clot that quickly stems the bleeding.



In testing, rat models injected with synthetic platelets prior to injury stopped bleeding in half the time of untreated models. Untreated models injected 20 seconds after injury stopped bleeding in 23 percent less time than models left untreated.



In another comparison, the artificial platelets resulted in clotting times about 25 percent faster than wounds treated with recombinant factor VIIa, which is the current state of the art treatment for uncontrolled bleeding in surgery and emergency rooms. While the recombinant factor is used on various injuries, its cost can be in the tens of thousands of dollars per treatment and is not used in patients suffering head or spinal cord injuries, due to risk of complications.



Lavik said her team made platelets from polymers already used in treatments approved by the Food and Drug Administration in hopes the new treatment might be approved faster. They also built the parts of the synthetic platelets that bind to natural platelets from relatively short pieces of proteins because they're more stable than longer pieces and cheaper.



To avoid formation of an artificial clot, each synthetic platelet is built with a surrounding water shield. Fluorescing compounds showed the synthetic platelets not bound in clots were flushed from the rat model's system in a day. No ill effects were seen in the following week.



Testing also showed the synthetic platelets remain viable after sitting on a shelf for at least two weeks.



Lavik is seeking grants to further test the platelets.



Source: Kevin Mayhood


Case Western Reserve University

$500,000 Gruber Neuroscience Prize Awarded To Hall, Rosbash And Young

The 2009 Neuroscience Prize of The Peter and Patricia Gruber Foundation is being awarded to Jeffrey Hall, professor of neurogenetics at the University of Maine; Michael Rosbash, professor and director of the National Center for Behavioral Genomics at Brandeis University; and Michael Young, professor and head of the Laboratory of Genetics at Rockefeller University. On October 18, at the annual meeting of the Society for Neuroscience in Chicago, Illinois, these three distinguished scientists will receive this prestigious international award for their groundbreaking discoveries of the molecular mechanisms that control circadian (daily) rhythms in the nervous system. Their research was the first to establish a simple relationship between single genes and a complex behavior.



"The combined discoveries of Jeffrey Hall, Michael Rosbash and Michael Young are stunning in their creativity, breadth and significance. These researchers began with a complicated animal behavior, established that single genes can define specific aspects of this behavior and determined mechanistically how such genes act," says H. Robert Horvitz, David H. Koch Professor of Biology at MIT. "Hall, Rosbash and Young have not only defined the genetic, molecular and biochemical bases of a complex animal behavior but have also established a paradigm for how such analyses should be done."



Before Hall, Rosbash, and Young published their seminal studies on the molecular underpinnings of the circadian rhythms of the fruit fly, Drosophila melanogaster, many people questioned whether a compelling relationship between genes and behavior could be established. By the early 1970s, the first fruit fly mutants with altered circadian rest/active cycles had been identified - making a case for the genetic control of behavior - but the mechanism behind the phenomenon remained unknown. What was running the internal biological clock in Drosophila?



In 1984 came the first breakthrough. That year Hall and Rosbash, working at Brandeis University, and Young, working at Rockefeller University, simultaneously cloned the period (per) gene of Drosophila. That pivotal discovery led to subsequent studies from all three labs that eventually unmasked the general molecular mechanism for circadian clocks: a transcriptional feedback loop that oscillates during the 24-hour cycle.



Hall and Rosbash demonstrated, for example, that per gene products exhibit oscillations for their concentrations and that during a daily cycle the per protein represses transcription of the very gene that specifies that "final" product. (Transcription is a gene's ability to copy its DNA sequence into messenger RNA, a necessary step for translating the gene into a protein that performs a specialized function in the cell). Young identified per's partner gene, timeless (tim), and then showed that when these two genes' protein products (PER and TIM) reach certain levels, they bind together in the cell's cytoplasm and are transported back into the nucleus, where primarily PER shuts down the genes that made them. After a few hours, the proteins degrade, the genes start up again - and the cycle begins anew.



As Hall, Rosbash, and Young continued their research, the fundamental workings of this complex feedback system came into even sharper focus. They discovered other genes and protein products that play critical roles in regulating the loop. They found that mutations affecting any of these genes had effects on Drosophila's molecular rhythms - and on its behavior. They also identified how certain stimuli, most notably the light-dark cycle, help regulate the feedback loop in order to reset the clock everyday to operate in synch with natural environmental cycles (a key and universal feature of daily rhythms).



When other researchers investigated the clock mechanisms in mammals, they found them to be strongly analogous to what Hall, Rosbash, and Young had found in Drosophila. Thus, the uncovering of the mechanism in the fruit fly - a tour de force of genetics and molecular biology - has paved the way for the study of human circadian genetics.



"Practically all biological creatures thus display a circadian rhythm, whether fruit fly or man, as some species are active during night and others during daytime. This astounding ability depends on an intricate molecular mechanism that, once developed, has been conserved throughout evolution," says Sten Grillner, Director of the Nobel Institute for Neurophysiology at the Karolinska Institutet. "To reset the biological clock takes many days, as all intercontinental travelers are forced to experience - for shift-workers it is more serious, it creates stress and fatigue that over many years can lead to harmful medical conditions."



Source:
Alyson O'Mahoney


Robin Leedy & Associates, Inc.

Mechanism In Memory Development Discovered In Flies That May Help Parkinson's Patients

Before swatting at one of those pesky flies that come out as the days lengthen and the temperature rises, one should probably think twice. A University of Missouri researcher has found, through the study of Drosophila (a type of fruit fly), that by manipulating levels of certain compounds associated with the "circuitry" of the brain, key genes related to memory can be isolated and tested. The results of the study may benefit human patients suffering from Parkinson's disease and could eventually lead to discoveries in the treatment of depression.



"The implication for human health is that it could influence our understanding of the cognitive decline associated with Parkinson's disease and depression in humans," said Troy Zars, MU assistant professor of biological science in the College of Arts and Science.



The idea that animals have a system that can match the quality of a memory with the significance of the memory is well established. If the event is significant, the memory and detail surrounding it is much stronger, lasts longer and is more easily recalled compared to more insignificant or common events. The problem the study addresses is the understanding of the mechanism by which that occurs.



"We have developed a strategy to address how this matching occurs, so we can 'turn that crank' over and over again. It allows us to answer the questions, 'What gene is it" How does it function" How does it interact with other proteins"' We can find brand-new, completely unexpected things," Zars said.



A major goal of neuroscience is to discover and study memory-forming structures within a brain. Zars said he works with Drosophila because they are a well-established genetic model, have a relatively less complex brain than the mouse or human (250,000 neurons versus 100 billion neurons), and have a broad repertoire of behaviors.



Memory in the flies was tested using a specialized chamber in which single flies were allowed to wander freely. The chamber was outfitted with heating elements. When the fly moved to a particular side, the whole chamber rapidly heated to an uncomfortable temperature. The flies eventually learned, or remembered, to avoid that half if brain "circuitry" is functioning properly. A mutation in certain flies, however, altered the levels of serotonin and dopamine, which resulted in lower memory scores.



"This research is important because by studying a simple brain it will help us ultimately understand complex neural systems," Zars said. Zars' study was published this week in Proceedings of the National Academy of Sciences.







Source: Bryan E. Jones

University of Missouri-Columbia

Discovery Of Protein That Contributes To Cancer Spread

In an important finding published online in Developmental Cell, researchers at Albert Einstein College of Medicine of Yeshiva University, along with collaborators at Massachusetts Institute of Technology, have identified a protein likely responsible for causing breast cancer to spread.



Metastatic cancer occurs when cancer cells from the original tumor travel to distant sites via the blood system. Most cancer deaths are due to cancer that has spread to other organs. Trying to stop cancer before it metastasizes is the main goal of cancer treatments. Upon diagnosis, 6 out of 10 breast cancer patients have cancer that is still in its primary location making the potential discovery of a marker for invasive cancer of tremendous value that could better inform treatment options.



Until now, early markers of metastatic breast cancer have been hard to find. However, in the Einstein-led study, researchers have identified a protein that is a promising candidate for a metastatic breast cancer marker.



The protein, called Menainv is present in invasive cells within a breast tumor. These cells move into surrounding tissue and eventually to blood vessels. Menainv is not on breast tumor cells that stay put (resident cells). This is the first time that a protein has been shown to contribute to the invasive and metastatic ability of tumor cells, rather than just being an 'innocent bystander' that shows up when cells are invading, strengthening the potential use of this protein as a marker.



The research was conducted under the direction of and in the laboratories of John S. Condeelis, Ph.D., Einstein professor and co-chair of anatomy and structural biology and co-director of Gruss Lipper Biophotonics Center and Frank B. Gertler, Ph.D., Ross Scholar Professor of Biology at MIT.



The latest research was aided considerably by the work of Jeffrey B. Wyckoff, principal associate, department of anatomy and structural biology at Einstein who, with Dr. Condeelis, developed the in vivo invasion assay used to isolate metastatic tumor cells from breast tumors thereby implicating Mena as an important gene for metastasis.



Evanthia T. Roussos, an M.D.-Ph.D. student in Dr. Condeelis' lab and primary co-author of the study, explains, "We have micro-needles filled with growth factors and tissue that we insert into a tumor on an anesthetized mouse. If a cell is invasive, within four hours, it will crawl into the needles. We found that mouse breast tumor cells that we engineered to contain Menainv were invasive whereas cells that did not have Menainv were not."



Another finding from the study that has important implications for patient treatment is that tumor cells harboring Menainv are less likely to be responsive to newer breast cancer treatments that inhibit epidermal growth factor receptors (EGFR). Epidermal growth factor (EGF) has been shown to increase a breast cancer cell's invasive potential. The study investigators propose that drugs which inhibit EGF may lack effectiveness on tumor cells that express Menainv. That's because Menainvcells are so sensitive to EGF that even the small amount of EGF signal that the drugs fail to block may be enough to stimulate EGF receptor and promote tumor cell migration and metastasis.
















If Menainv behaves similarly in humans as it does in mice, it would be an especially attractive marker for metastatic breast cancer because the structure of Menainv would enable an antibody or a PCR assay to be developed to identify it. Such an antibody or PCR assay could be used to diagnose the presence of Menainv in biopsies and blood samples allowing doctors to identify breast cancer patients who are more likely to have progressive disease and recommend the appropriate treatment.



The current study builds on previous research by Dr. Condeelis' group which identified Menainv as the isoform of Mena that is over expressed in the invasive and metastatic subpopulation of tumor cells in breast tumors. The current study shows that Menainv forces tumor cells in mammary tumors of mice to become invasive and eventually metastasize to the lung.







The primary co-authors of the paper are Ulrike Philippar, MIT, Merck Research Laboratories and Evanthia Roussos, Albert Einstein College of Medicine, Department of Anatomy and Structural biology, Gruss Lipper Biophotonics Center. Other authors include Matthew Oser, Yarong Wang and Jeffrey B. Wyckoff of Einstein; Sumanta Goswami of Einstein and Department of Biology, Yeshiva University; Hideki Yamaguchi, Einstein and now at Tokyo University of Pharmacy and Life Sciences; Hyung Do Kim and Douglas A. Lauffenburger, MIT; Silvia Giampieri, Cancer Research UK, London Research Institute; and Erik Sahai, Einstein and Cancer Research UK, London Research Institute.



About Albert Einstein College of Medicine of Yeshiva University



Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. It is the home to some 2,000 faculty members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D. programs) and 380 postdoctoral investigators. Last year, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long Island - which includes Montefiore Medical Center, Einstein's officially designated University Hospital - the College runs one of the largest post-graduate medical training program in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit aecom.yu.



Source: Michael Heller


Albert Einstein College of Medicine

Efficacy Of M2 Vaccines Increased By Cell Death Suppression

Significant public attention has recently been focused on the development of new anti-influenza (flu) vaccines that provide protection against a broad spectrum of viral strains. One proposed strategy is to utilize conserved viral protein, M2. Clinical trials of M2-containing influenza vaccines were recently initiated by US and European companies.



Scientists from Cure Lab, Inc. in collaboration with Boston University School of Medicine published new findings indicating that unmodified M2 may have a negative effect on anti-influenza vaccination. The researchers also demonstrated how this detrimental effect of M2 can be eliminated, thereby allowing any future M2-containing vaccine to be both broadly protective as well as safe. This study appears in the January 16th issue of the online journal PLoS ONE, which provides free access of its publications to scientists and the general public.



Annual vaccinations against seasonal flu are known to be insufficient to fully prevent disease. The cause of this is a single predicament: current vaccines predominantly target two viral surface proteins, hemaglutinin and neuraminidase that are constantly mutating. Thus, a particular vaccine can be protective against a viral strain carrying matching hemaglutinin and neuraminidase, but will lose efficacy as soon as these proteins change (gradually or even in a single step). The latter process is known to continuously occur in nature.



In their attempts to make current strain-specific vaccines effective, the World Health Organization (WHO) has to annually predict the most likely viral strains that will be responsible for the next seasonal flu outbreak. This process takes place just a few months before flu season starts. This process is error prone, that is, it is possible that the vaccine may be manufactured against non-matching viral strains and not the one that may actually cause the epidemic. Moreover, as long as vaccines remain to be strain specific, it will be impossible to both manufacture them in advance and to enable their stockpiling. This, in turn, drives up the vaccine cost and makes its efficient world-wide distribution almost impossible.



Finally, the new strains of flu virus usually emerge in Asia and then migrate to Europe and North America. Recently, Indonesia demonstrated its reluctance to cooperate with WHO and restricted information exchange regarding the nature of a novel influenza strain. Several other countries in the region were sympathetic to Indonesia's actions. These and many other problems will never be fully resolved until anti-flu vaccines cease to be strain-specific.



However, all of the problems mentioned above could be alleviated by the development of a new generation of vaccine. Such a vaccine should be based on conserved flu proteins, which to a significant degree remain constant among all flu strains.
















In addition to continuously mutating proteins, flu virus also possesses nucleoprotein (NP), and major matrix protein (M1), that reside inside the viral particle, and do not generate a strong antibody response. This may be the reason why these proteins do not naturally undergo significant mutagenesis and posses a striking degree of similarity among all influenza strains. Another conserved flu protein that is strongly expressed in virus-infected cells is a nonstructural protein 1 (NS1).



In the March issue of the scientific journal Influenza and Other Respiratory Viruses, Massachusetts-based biotech company Cure Lab, Inc. reported that vaccinating mice with a combination of genes encoding these three conserved proteins of flu virus, NP, M1 and NS1, protected mice against human as well as avian strains of flu virus. In particular, this included an experiment demonstrating protection against bird flu virus that encodes type 5 hemaglutinin or H5. The challenge with this viral strain was used as a model of potential pandemic outbreak, which many believe may be caused by spreading of avian H5N1 virus to the human population. Moreover, in the same paper, Cure Lab reported that the same combination of three conserved viral genes provided significant protection against H5-carrying influenza strain in the chicken model.



In addition to Cure Lab, several other companies are also pursuing attempts to utilize genes encoding conserved flu proteins as vaccine components. This includes the California-based company Vical, known for its chemical adjuvant Vaxfectin. Vical included another extremely conserved flu protein, M2 into its proposed anti-flu product. M2 is present in low copy numbers at the surface of influenza viral particles, but is expressed abundantly on the surface of infected cells. Most of the research groups, including British biotech company, Acambis, have attempted to utilize only an extracellular domain of M2 protein called M2e. Despite some encouraging results demonstrating that if used at very high doses, M2e may induce a protective antibody response, the current opinion in the field is that it should be used only as a supplement to more potent antigens. One of the reasons may be that M2e lacks possible protective epitopes located within the intracellular and trans-membrane parts of M2. In addition, at least one recent report demonstrated that vaccination with M2e-encoding gene used in combination with the NP gene, exacerbated disease and increased mortality in pigs. In contrast to the Acambis strategy, Vical has included the gene encoding a full-size M2 into its vaccine prototype. The company reported that it had initiated clinical trials already.



"As it often happens, path-finding research starts as a result of an unexpected failure," said Dr. Alex Shneider, the senior author on the PLoS ONE paper and Cure Lab's CEO. "Initially, we believed that simply adding a gene encoding the full size M2 to our previously developed vaccine prototype would further increase the protective properties of the vaccine. Instead, we observed exactly the opposite".



Puzzled with such a counterintuitive result, Cure Lab went from product development to a basic science approach and asked the question: "Why would M2 decrease the efficiency of influenza vaccination?" Interestingly, for a number of years M2 was known to be insufficiently immunogenic in vaccine studies, which in fact, necessitated the utilization either of high doses of M2 or the shift to M2e-peptide as mentioned above. Earlier, Cure Lab demonstrated that M2 on its own may kill the cells producing this protein (uninfected with influenza). The scientists hypothesized that this is the underlying reason for the undesirable effect of M2 on vaccination. If this assumption was correct, then it would immediately suggest how to resolve the problem.



In order for M2 not to be able to exercise its negative functions, the protein should be "trapped" or neutralized in such a manner that prevents it from cell killing. Therefore, Cure Lab fused M2 with other proteins constituting a vaccine in such a way that NP, M1 and NS1 proteins restrict M2 functionality. This specific composite poly-protein, which did not kill the host cells, was selected based on its biochemical properties and cell-based assays.



Further animal testing demonstrated that the fusion construct containing all four conserved influenza proteins including "neutralized" M2, possesses much more promising protective properties than the same poly-protein without M2. "It shows us that the M2-gene can indeed be a valuable component of a novel anti-influenza vaccine if its negative effect is eliminated. One such approach is delineated in the PLoS ONE publication. Other possibilities are prevention of M2-induced cell death by introduction of specific mutations into the M2 gene or combining vaccination with drugs targeting M2, for example, amantadine." said Dr. Alex Shneider.



"Our data does not necessarily indicate that clinical trials of vaccines utilizing genes encoding a full-size influenza M2 protein is unsafe." stated Dr. Petr Ilyinskii, Principal Scientist at Cure Lab. "At the same time, it may suggest that the efficacy of M2-containing vaccines is not optimal for clinical trials and medical applications".



Meanwhile, pandemic flu continues to be one of the major threats to society. It remains to be seen whether it will be eliminated through the development of novel vaccines similarly to smallpox and polio or, at least, becomes controllable.







Citation: Ilyinskii PO, Gambaryan AS, Meriin AB, Gabai V, Kartashov A, et al (2008) Inhibition of Influenza M2-Induced Cell Death Alleviates Its Negative Contribution to Vaccination Efficiency. PLoS ONE 3(1): e1417. doi:10.1371/journal.pone.0001417



Click here to link to the published article online.



Disclaimer


This press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions. Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information.



Source: Helen Kress


Public Library of Science

Illumina Announces Delivery Of The First Genome Through Its Individual Genome Sequencing Service

Illumina, Inc. (NASDAQ:ILMN) announced that it has delivered Hermann Hauser's genome sequence. Dr. Hauser, Partner, Amadeus Capital Partners Ltd, is the first consumer to purchase Illumina's individual genome sequencing service working with his physician, Michael Nova, MD, of Pathway Genomics. The genome was completed in Illumina's CLIA-certified and College of American Pathologists (CAP) accredited laboratory using the Genome Analyzer technology. Over 110 billion base calls were generated, delivering over 30X coverage of the genome. Data analysis showed 300K novel SNPs in the genome that have not been documented elsewhere. This discovery demonstrates the power of whole genome sequencing as an exploratory tool, as these SNPs were novel but not necessarily unique.


"We are very excited to be delivering our first individual genome sequence to Hermann Hauser," said Jay Flatley, President and CEO of Illumina. This is a landmark since just two months ago we launched the availability of this service from Illumina. The experience we created for Hermann was not only one of personal genetic exploration, but one that points to a future where genome sequencing will become a routine practice and the information generated will enable physicians to make better healthcare decisions for the individual. This information has long term value for Hermann as he can continue to access it and gain personal genomic insights as new discoveries are made.


Dr. Hauser's genome was delivered by a team consisting of his physician, Dr. Michael Nova, a bioinformatics specialist and geneticist at Illumina's San Diego headquarters on Thursday, August 20, 2009. The visit included a consultation, facility tour and ceremony during which Dr. Hauser's genome was delivered on an iMac® computer using GenomeStudio® software as a genome browsing interface.


Hermann Hauser is one of the first of a small, select group of individuals who have had their genome sequenced. "Going through Illumina's process was very exciting for me personally. I am looking forward to the information on gene variants that will give my doctors guidance on effective treatments and drug dosage based on pharmacogenetic information, for any future medical condition I may develop. This is the beginning of personalized medicine and I am delighted to be there at the start of it. As an early investor in the gene sequencing technology used in this work, I am proud that Illumina has introduced this service to consumers. It fulfills an early dream to substantially reduce the cost of whole genome sequencing," said Hauser.


Dr. Hauser is a pioneer member of a growing community that is driving education and exchange of information for those who have had their genomes sequenced. As more information becomes available, participants will be in a position to mine their personal genome sequence data to understand their identity in ways which have never been possible before. For more information about Illumina's individual genome sequencing service, please visit everygenome.


Source

Illumina

Breaking The Nanometer Barrier In X-ray Microscopy

Argonne National Laboratory scientists in collaboration with Xradia have created a new X-ray microscope technique capable of observing molecular-scale features, measuring less than a nanometer in height. Combining x-ray reflection together with high resolution x-ray microscopy, scientists can now study interactions at the nanometer-scale which often can exhibit different properties and lead to new insights. Improving our understanding of interactions at the nanoscale holds promise to help us cure the sick, protect our environment and make us more secure.



This novel technique will lead to a better understanding of interfacial reactions at surfaces, such as ion adsorption, corrosion, and catalytic reactions. In particular, this method extends the capability of x-ray microscopy to observe sub-nanometer-sized interfacial features directly and in real time. This non-invasive approach complements the more widely used scanning probe microscopies and can image the topography of a solid surface without using probe-tips near the surface.



Argonne researchers together with Xradia, a firm specializing in x-ray optics and x-ray microscope systems, have achieved sensitivity to sub-nanometer sized features by using a phenomenon known as phase contrast. This breakthrough makes it possible to look directly at individual steps on a solid surface, borrowing a technique used previously in electron microscopy, "The ability to see individual nanometer-scale features is an important benchmark for X-ray microscopy" states Paul Fenter, Argonne National Laboratory Physicist. "Understanding interfacial reactivity is vital to many areas of science and technology, from the corrosion of metals to the transport of contaminants in the environment." Steve Wang of Xradia adds, "This technique opens up the possibility of watching these processes directly and will provide fundamentally new opportunities for understanding them."



This is a significant advance towards understanding the reactivity of solid-surfaces. Future studies will extend these measurements to the observation of real-time processes of mineral surfaces in contact with water. Employing a novel x-ray microscope setup developed by Xradia, and measurements performed at Argonne's Advanced Photon Source, home of the most brilliant X-ray source in the Western Hemisphere, was central to the teams' success.







The research, funded by the U.S. Department of Energy's Office of Basic Energy Sciences, was carried out by a team at Argonne National Laboratory Chemistry Division, scientists including Paul Fenter, Changyong Park, Zhan Zhang, in collaboration with Steve Wang from Xradia. The results were recently published in Nature Physics (VOL 2, pages 700-704, 2006).



Xradia, Inc. is a privately held company established in 2000 to commercialize high-resolution x-ray microscopy systems for nondestructive inspection and nano-scale imaging. Initially targeted at failure analysis in the semiconductor IC industry, subsequent developments have led to a suite of commercial x-ray imaging products that have permitted expansion into markets that include metrology in semiconductor IC production, scientific equipment, biomedical research and nanotechnology development.



The nation's first national laboratory, Argonne National Laboratory conducts basic and applied scientific research across a wide spectrum of disciplines, ranging from high-energy physics to climatology and biotechnology. Since 1990, Argonne has worked with more than 600 companies and numerous federal agencies and other organizations to help advance America's scientific leadership and prepare the nation for the future. Argonne is managed by the UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.



Contact: Eleanor Taylor


DOE/Argonne National Laboratory

News From The American Chemical Society June 18, 2008

Prions are not degraded by conventional sewage treatment processes



Scientists in Wisconsin are reporting in a paper scheduled for the July 1 issue of ACS' Environmental Science & Technology that typical wastewater treatment processes do not degrade prions. Prions, rogue proteins that cause incurable brain infections such as Mad Cow disease and its human equivalent, variant Creutzfeldt-Jakob Disease, are difficult to inactivate, resisting extreme heat, chemical disinfectants, and irradiation. Until now, scientists did not know whether prions entering sewers and septic tanks from slaughterhouses, meatpacking facilities, or private game dressing, could survive and pass through conventional sewage treatment plants.



Joel Pedersen and colleagues used laboratory experiments with simulated wastewater treatment to show that prions can be recovered from wastewater sludge after 20 days, remaining in the "biosolids," a byproduct of sewage treatment sometimes used to fertilize farm fields.



Although emphasizing that prions have never been reported in wastewater treatment plant water or biosolids, the researchers note that existing tests are not sufficiently sensitive to detect the extremely low levels of prions possible in those materials. - AD



ARTICLE: "Persistence of Pathogenic Prion Protein during Simulated Wastewater Treatment Processes" dx.doi/10.1021/es703186e



CONTACT:

Joel A. Pedersen, Ph.D.

University of Wisconsin

Madison, Wisconsin



New test for more reliable product expiration labels



Beer gets a "skunky" taste. Wine develops an unpleasant flavor termed "light-struck." And exposure to light causes off flavors, colors, and aromas in hundreds of other foods and beverages and decreases shelf life. Now, researchers in Italy report development of a more reliable method for predicting shelf-life that accounts for light sensitivity for the first time and may help consumers choose fresher, tastier food products. Their study is scheduled for the June 25 issue of ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.



In the new study, Lara Manzocco and colleagues note that the bright, intense light of retail displays is widely known to cause the formation of off-flavors, loss of nutrients, and color fading in food and beverages. But conventional methods to test the shelf-life of these products focus on the effect of heat and ignore the effect of light, leading to underestimations in shelf-life shown on product expiration labels. A more reliable test is needed, the researchers say.



The scientists exposed a soft drink containing saffron, which contains light-sensitive substances, to different levels of light at increasing temperatures. They found that the beverage grew lighter in color as light intensity increased, confirming that light can cause a dramatic decrease in beverage quality. Based on these observations, the scientists developed a new mathematical model that measures light-sensitivity as well as temperature to provide a more reliable method for predicting shelf-life. - MTS
















ARTICLE: Shelf Life Modeling of Photosensitive Food: The Case of Colored Beverages" dx.doi/10.1021/jf800072u



CONTACT:

Lara Manzocco, Ph.D.

UniversitГ  di Udine

Udine, Italy



New research reports that 12 million molecules share 143 basic shapes



Chemists in Ohio have discovered that half of all of the known chemical compounds in the world have an amazing similarity in sharing only 143 basic molecular shapes. That sharply limits the number of molecular building blocks that chemists often deploy in efforts to develop new drugs and other products, the researchers say in a study scheduled for the June 20 issue of the bi-weekly ACS' Journal of Organic Chemistry.



Alan H. Lipkus and colleagues note that researchers have known for years that certain features of molecules, such as rings of atoms and the bonds than link them together, appear time after time in hundreds of life-saving medications, food additives, and other widely used products.



Scientists often tend to focus on these well-known types of molecular scaffolding in their quest to select the most promising rings, linkers, and other components for building new drugs while overlooking less familiar structures, the researchers say.



In the new study, they analyzed the chemical frameworks of more than 24 million organic substances found in the ACS' Chemical Abstracts Service (CAS) Registry, the world's most comprehensive database of disclosed molecules. They found that half of the substances could be described by only 143 basic framework shapes. By paying more attention to a multitude of other molecular shapes, chemists might discover an array of useful rings, linkers, and other building blocks for tomorrow's drugs and other medical, commercial, and industrial products, the study concluded. - MTS



ARTICLE: "Structural Diversity of Organic Chemistry. A Scaffold Analysis of the CAS Registry" dx.doi/10.1021/jo8001276



CONTACT:

Eric Shively

Chemical Abstracts Service

Columbus, Ohio 43210



Building giant 'nanoassemblies' that sense their environment



Researchers in Texas are reporting the design, construction, and assembly of nano-size building blocks into the first giant structures that can sense and respond to changes in environmental conditions. The study, scheduled for the July 9 issue of ACS's Nano Letters, a monthly journal, terms those structures "giant" because they are about the size of a grain of rice - millions of times larger than anything in the submicroscopic realm of the nanoworld.



In the new study, Pulickel M. Ajayan and colleagues point out that such structures are a step toward the development of futuristic nanomachines with practical applications in delivering medicines to patients, labs-on-a-chip, and other products. Until now, scientists have had difficulty in using nanomaterials to build more complex, multifunctional objects needed for those applications.



The researchers describe development of a hybrid nanowire consisting of segments with water-repelling carbon nanotubes on one end and water-attracting metal nanowires on the other end. In laboratory tests, they showed that the nanowires could assemble themselves into larger, more complex structures when placed in water. The structures also sensed and responded to their environment by making movements when exposed to chemicals, magnets, and light. The findings "could lead to the creation of smart materials that are a cornerstone for the development of nanotechnology-based applications," the study notes.



ARTICLE: "Controlled Manipulation of Giant Hybrid Inorganic Nanowire Assemblies" dx.doi/10.1021/nl080407i



CONTACT:


Pulickel M. Ajayan, Ph.D.

Rice University

Houston, Texas 77251-1892



Chemists develop healthier foods



From carrots to grapefruits to tortillas, researchers worldwide are giving common foods a more nutritious makeover by removing unhealthy substances and adding or enhancing those that may help fight diseases such as cancer and heart disease, according to an article scheduled for the June 23 issue of Chemical & Engineering News. Some of these products could soon appear at a grocery store near you.



In the C&EN cover story, Associate Editor Rachel Petkewich points out that, amid growing consumer interest in leading a healthier lifestyle, scientists are identifying an increasing number of disease-fighting substances in foods and using them to enhance food crops. As evidence for this skyrocketing interest in healthier foods, the article notes that the number of published papers exploring the disease-fighting properties of food components has quintupled since 2003. Scientists have already developed carrots with super-high antioxidant levels. Other foods designed to target cancer, high cholesterol, and other health conditions may soon be on the way.



But creating healthier foods that are still appealing to consumer taste can be tricky, as changing certain food components makes flavor and texture unappetizing. Scientists are now working on creating substances that can boost nutrition without loosing the qualities consumers find appealing.



ARTICLE: "Devising Healthier Foods" pubs.acs/cen/coverstory/86/8625cover.html







The American Chemical Society - the world's largest scientific society - is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.



Source: Michael Woods


American Chemical Society

Gene Therapy Of AIDS

Specialists of the V.A. Engelgardt Institute of Molecular Biology, Russian Academy of Sciences, and the "Vector" Main Research Center of Virology and Biotechnology created and tested on the cell culture three genetic structures capable to suppress reproduction of human immunodeficiency virus (HIV-1) in human cells.


At present, the virus is fought against by chemical agents. The drugs subscribed to the patients act predominantly on key HIV-1 enzymes - reverse transcriptase, invertase and protease. There are a lot of antiviral drugs, but they are often ineffective as HIV mutates quickly and acquires drug resistance. And these drugs are, one should note, toxic and very expensive.


Meanwhile, the human organism's cells possess powerful natural mechanism which should regulate the work of genes including viral ones. It is called RNA-interference. In an extremely simplified form, RNA-interference is damage to a certain RNA sequence with participation of a different, "defending" RNA molecule. This system prevents viral infection, unless viruses had learned to cut it off in the course of evolution. Researchers from countries including Russia are developing the artificial RNA-interference system. It is non-injurious to the patient and, due to high specificity of action, does not damage its own RNA in cells infected by the virus.


To fight against HIV, Russian biologists have created three genetic structures. These structures contain short nucleotide sequences that find the most conservative molecules among all RNA molecules, that is, sequences that do not change quickly and are important to the virus. These sequences are then "damaged". The structure also includes the gene of green fluorescent protein, which allows to determine is the gene structure has entered the cell or not.


The researchers embedded the gene structures created by them into cultivated lymphoid cells. Cells which have been penetrated by the fluorescent protein begin to glow with green. Within 24 and 72 hours after introduction of genetic structures, the cells were infected by human immunodeficiency virus (GKV-4046 culture), and several days later the researchers assessed the degree of viral welfare by specific antigen accumulation. It has turned out that the genetic structures significantly suppress viral reproduction.


The extent of damage to viral RNA depends on the viral dose received by the cell itself and on the sequence of the structure per se. The sequence aimed at the reverse transcriptase area of viral genome turned out to be the most efficient, being capable of suppressing the viral production in the cells by 91 to 98 percent within three days.


In the researchers' opinion, similar genetic structures can be used in AIDS gene therapy. At present, the researchers continue the effort on creation of efficiently operating structures, including the ones that are able to overcome high virus mutation.


INFORMNAUKA (INFORMSCIENCE) AGENCY

informnauka.ru/

Smell Is 'Noisy' And 'In Shades Of Grey' - Scientists Debunk Ancient Lock-And-key Theory

University of Manchester scientists have overturned the 2,500-year-old theory that smell is detected by simple lock-and-key codes - using maggots with only one working olfactory sensory neuron (OSN), a nose with one nerve cell.



It was thought that smells are detected by simple lock-and-key codes. Instead it appears that there is a combination of precise and 'fuzzy' coding that allows organisms to sharpen their response to odours, rather like the dither that is famously used to improve computer performance. Whilst fuzzy coding is known to occur in the central brain, this is the first time it has been shown in the periphery.



Dr Matthew Cobb, at the University's Faculty of Life Sciences, explains: "We have been able to address a problem that people have been trying to resolve for 2,500 years, since the Greek philosopher Democritus suggested that nice smells came from smooth, round atoms and bad smells came from spiky atoms.



"Until now, people have thought that smell works by a simple lock-and-key code where each smell molecule fits into one or more receptors that recognise it. If the smell is there, then the receptors will respond.



"However we have found this to be an over-simplification. It is not just a lock-and-key system. Sometimes a smell comes along and doesn't 'turn the lock'.



"We first set out thinking we would crack the code of locks and keys but we were driven to a new conclusion by the data. We tested for everything, controlled everything, but we found our starting place was wrong. It was a very exciting turn of events."



Dr Cobb and his colleague Dr Cathy McCrohan, together with their PhD student Derek Hoare, have published their study in Journal of Neuroscience. They used Drosophila larvae (maggots) with only one working olfactory sensory neuron (OSN) - a nose with one nerve cell. Although it might seem an unlikely animal to study, the "wiring diagram" of a maggot's nose is exactly the same as that in a human, but much simpler. The scientists recorded the activity in the maggot's nose, to see exactly how smells were detected. The test group was compared to a control group of normal maggots with a full complement of twenty-one working OSNs.



As expected, some OSNs showed consistent, precise lock-and-key responses - either excitation or inhibition - in response to a given odour. But to the scientists' surprise, most cells also showed variable responses - "fuzzy coding"; sometimes they responded to a given odour and sometimes they did not. This variability was real: it was not related to odour type, concentration, stimulus duration, or the genetic make-up of the individual maggot, and it was seen in both test and control groups. They concluded that the peripheral code combines precise coding with fuzzy, stochastic responses in which neurons show apparent unpredictability in their responses to a given odour.



They now believe that fuzzy coding occurs in other organisms, is translated into differing degrees of activation in the brain, and forms a key component of odour recognition in the first stages of olfactory processing.
















Dr McCrohan explains: "The nose gives us insight into the brain - it's not a computer, it's not precise, it's fuzzy. This may be a consequence of way the receptors are built and must be used in some way as part of the process by which the brain perceives an almost infinite variety of odours.



She adds: "These data explained previously mysterious findings that people had reported but were unable to fit into the 'lock and key' model.



"These findings had people scratching their heads, now we can explain them. Fuzziness is true, a real phenomenon that forms a key part of how we detect smells."



The pair now plans to take the research further. So far they have been using pure smells but real smells are highly complex mixtures of chemicals. In addition the single cell maggot nose is extremely simple; many animals possess hundreds of thousands of OSNs and humans have millions.



Dr Cobb says: "We've been using pure smells but real smells are complicated blends; for example a cherry has 200 different molecules. Maybe when you detect a real smell, you use a combination of precise and fuzzy responses - to give yes/no/maybe - forming overall recognition. This is rather like face recognition in which you recognise the same face, even from different angles. So we would like to see how maggots respond with blends.



"We also want to extend the study to other organisms such as beetles, which have nearly as many olfactory receptor types as humans. Other scientists who work with mice or humans could rise to the challenge. I presented this study to a scientific meeting on the sense of smell in Slovenia. It was controversial but well received. People went away convinced they need to look again at data that they have thrown away or ignored.



"Science works by analogy. In the past, people believed the body was like a machine. Then, with the advent of technology, we first thought the brain was like a computer, then like the worldwide web. What we've found here is that these analogies can be misleading. Animals are not machines: information processing in the nervous system involves a huge amount of unpredictability - even in a maggot."




A copy of the paper 'Precise and Fuzzy Coding by Olfactory Sensory Neurons' by Derek J. Hoare, Catherine R. McCrohan and Matthew Cobb is also available here.



The University of Manchester Faculty of Life Sciences, with more than 1,000 people involved in research, 1,700 undergraduate students and an annual total budget of ВЈ65 million, is one of the largest and most successful unified research and teaching organisations of its kind in Europe. See ls.manchester.ac.uk.