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