среда, 1 июня 2011 г.

Stanford Researcher Uses Living Cells To Create 'Biotic' Video Games

Video game designers are always striving to make games more lifelike, but they'll have a hard time topping what Stanford researcher Ingmar Riedel-Kruse is up to. He's introducing life itself into games.



Riedel-Kruse and his lab group have developed the first video games in which a player's actions influence the behavior of living microorganisms in real time - while the game is being played.



These "biotic games" involve a variety of basic biological processes and some simple single-celled organisms (such as paramecia) in combination with biotechnology.



The goal is for players to have fun interacting with biological processes, without dealing with the rigor of conducting a formal experiment, said Riedel-Kruse, an assistant professor of bioengineering.



"We hope that by playing games involving biology of a scale too small to see with the naked eye, people will realize how amazing these processes are and they'll get curious and want to know more," he said.



"The applications we can envision so far are on the one hand educational, for people to learn about biology, but we are also thinking perhaps we could have people running real experiments as they play these games.



"That is something to figure out for the future, what are good research problems which a lay person could really be involved in and make substantial contributions. This approach is often referred to as crowd-sourcing."



Applying their lab equipment and knowledge to game development, Riedel-Kruse's group came up with eight games falling broadly into three classes, depending on whether players directly interact with biological processes on the scale of molecules, single cells or colonies of single cells.



The results of their design efforts are presented in a paper published in the 10th anniversary issue of Lab on a Chip (the first issue of 2011), published by the Royal Society of Chemistry. The paper is available online now.



Initially, Riedel-Kruse said, the researchers just wanted to see whether they could design such biotic games at all, so this first round of development produced fairly simple games.



"We tried to mimic some classic video games," he said. For example, one game in which players guide paramecia to "gobble up" little balls, a la PacMan, was christened PAC-mecium. Then there is Biotic Pinball, POND PONG and Ciliaball. The latter game is named for the tiny hairs, called cilia, that paramecia use in a flipper-like fashion to swim around - and in the game enables kicking a virtual soccer ball.



The basic design of the games involving paramecia - the single-celled organisms used in countless biology experiments from grade school classes to university research labs - consists of a small fluid chamber within which the paramecia can roam freely. A camera sends live images to a video screen, with the "game board" superimposed on the image of the paramecia. A microprocessor tracks the movements of the paramecia and keeps score.
















The player attempts to control the paramecia using a controller that is much like a typical video game controller. In some games, such as PAC-mecium, the player controls the polarity of a mild electrical field applied across the fluid chamber, which influences the direction the paramecia move. In Biotic Pinball, the player injects occasional whiffs of a chemical into the fluid, causing the paramecia to swim one direction or another.



Riedel-Kruse emphasized that paramecia, being single-celled organisms, lack a brain and the capacity to feel pain. "We are talking about microbiology with these games, very primitive life forms. We do not use any higher-level organisms," he said. "Since multiple test players raised the question of exactly where one should draw this line, these games could be a good tool to stimulate discussions in schools on bioethical issues."



The game on the molecular level involves a common laboratory technique called polymerase chain reaction, or PCR, an automated process that lets researchers make millions of copies of an organism's DNA in as little as two hours.



In this game, called PolymerRace, the player is linked to the output of a PCR machine that is running different reactions simultaneously. While the reactions are running, the players can bet on which reactions will be run the fastest.



"The game PolymerRace is inspired by horse races, where you have different jockeys riding different horses," Riedel-Kruse said. "There is a little bit of bio-molecular logic involved and a little bit of chance."



The third game uses colonies of yeast cells that players have to distinguish based on their bread-vinegar like smell - olfactory stimuli anyone can experience just by walking into a bakery.



"The idea is that while we as humans play the game, we interact with real biological processes or material," he said. His research group thinks that aspect of the games could help motivate children and even adults to learn more about biology, which is increasingly important to society.



"We would argue that modern biotechnology will influence our life at an accelerating pace, most prominently in the personal biomedical choices that we will be faced with more and more often," Riedel-Kruse said. "Therefore everyone should have sufficient knowledge about the basics of biomedicine and biotechnology. Biotic games could promote that."



Riedel-Kruse wants to maximize the educational potential of these games to enable lay people to contribute to biomedical research. The team hopes that by publishing his group's initial efforts, other researchers in the life sciences will be prompted to explore how their own research could be adapted to "biotic" video games.



Other researchers have developed biologically relevant Internet-based video games such as Fold-It, which lets players try different approaches to folding proteins, and EteRNA, developed in a collaboration between Stanford and Carnegie Mellon University, which lets players propose new molecular structures for ribonucleic acids (RNA).



Fold-It and EteRNA were developed to address specific research questions. Fold-It was strictly a simulation; and although EteRNA will actually test some proposed structures in the laboratory, the players themselves do not have direct interaction with biological processes in real time as in Riedel-Kruse's biotic games.



Part of Riedel-Kruse's continuing work will include close collaborations with Rhiju Das, an assistant professor of biochemistry at Stanford and one of the developers of EteRNA, and Daniel Schwartz, professor in the School of Education at Stanford. The three co-founded the "Bio-X.Game Center" to develop and apply biotic games to education and research.



Source:

Louis Bergeron

Stanford University

Gourds Afloat: A Dated Phylogeny Reveals An Asian Origin Of The Gourd Family (Cucurbitaceae) And Numerous Oversea Dispersal Events

Knowing the geographic origin of certain plant groups is important for genetic improvement and conservation. We address the history of the economically important gourd family, Cucurbitaceae, using a multi-gene phylogeny for 114 of the 115 genera and 25% of the 960 species.


Our results reveal an Asian origin in the Late Cretaceous, followed by the repeated spread to Africa, America, and Australia via transoceanic long distance dispersal (LDD).


North American cucurbits stem from at least seven range expansions of Central and South American lineages; Madagascar was colonized 13 times from Africa; Australia was reached twelve times from Southeast Asia.


Proceedings of the Royal Society B: Biological Sciences


Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.


Proceedings of the Royal Society B: Biological Sciences

Recognition Given For Ground-Breaking Advancements In Digitalizing Health Data And Information

AMIA, the association for informatics professionals, honors four leaders in biomedical and health informatics on Nov. 13, 2010, with the annual presentation of its Signature Awards. The awards are to be announced on Monday, Nov. 15 at the Opening Session of AMIA's 34th Annual Symposium on Biomedical and Health Informatics in Washington, D.C., before an audience of more than 2,000 informatics professionals attending the event. Signature awards highlight extraordinary professionals working in the health industry, whose work transforms how health information and data is gathered, applied, and disseminated, and whose efforts result in elevated standards of care in the United States and beyond.



"The Signature Award recipients have made significant contributions to informatics, and in the process, have helped streamline the way data and information can be applied to patients," said AMIA Chairwoman Nancy M. Lorenzi, PhD, Assistant Vice Chancellor for Health Affairs, Vanderbilt University Medical Center. "This group of Signature Award recipients joins an impressive cohort of pioneers in health who are leading the way to more robust biomedical research, a more responsive public health sector, advancements moving more quickly and efficiently from bench to bedside, and more incisive clinical practice - all of which are made possible through the science of informatics," she added.



The Signature Awards and recipients are:

New Investigator Award



Recognizes an individual for early informatics contributions and significant scholarly contributions of scientific merit and demonstrated research excellence.



Adam Wright, PhD, is a research scientist in the Division of General Medicine at Brigham and Women's Hospital, Boston, and an instructor at Harvard Medical School. Dr. Wright focuses on clinical decision-support systems and data mining. He develops innovative tools for automated summarization of electronic health records (EHRs), and processing tools to support physicians as they document structured information in real time. He is the principal investigator for the Making Accurate Problem Lists in the EHR (MAPLE) project, which uses structured data in medical records to predict diagnoses and advise physicians of potential gaps in documentation of care. He also conducts research on malpractice, focusing on the use of decision-support systems to mitigate malpractice risk.

Virginia K. Saba Informatics Award



Recognizes a distinguished career that has made significant impact on the care of patients and the discipline of nursing. Recipient must demonstrate: use of informatics as transformative in patient care; visionary leadership; and enduring contribution to professional practice, education, administration, research, and/or health policy.



Judy Ozbolt, , PhD, RN, is a nursing informatics pioneer, whose long career includes faculty positions at the Universities of South Carolina, Pittsburgh, Michigan, Virginia, and Maryland, and at Vanderbilt University, and service as a Scholar at the Institute of Medicine. She led Nursing Terminology Summits from 1999 to 2008, which contributed substantially to the adoption of standards for nursing data by national and international standards organizations. Most recently, she chaired a Technical Expert Panel of a project commissioned by the Office of the National Coordinator of Health Information Technology to predict and mitigate unintended consequences of EHR adoption. Dr. Ozbolt was a founding board member of AMIA, the first chair of its Nursing Informatics Working Group, and a founding member of the editorial board of JAMIA. She also is a Fellow and past president of the American College of Medical Informatics, a Fellow of the American Academy of Nursing, and a Founding Fellow of the American Institute for Medical and Biological Engineering.

Don Eugene Detmer Award for Health Policy Contributions in Informatics
















Recognizes an individual who has made a significant contribution over the course of a career in health policy, conducted in accordance with the philosophy that all citizens and populations deserve a state-of-the-art health system that provides safe, effective, patient-centered, timely, efficient, and equitable health care services. The recipient exemplifies visionary leadership in the health policy realm, action-oriented advocacy work producing a regional, national or global result, advancement in thought leadership, and generating a sustainable contribution to the health system.



David Bates, MD, MSc, is chief of the Division of General Medicine at the Brigham and Women's Hospital, Boston; medical director of Clinical and Quality Analysis, IS; and a professor at both Harvard's Medical School and its School of Public Health. Dr. Bates has done extensive work evaluating the incidence and prevention of adverse drug events, and in improving efficiency and quality of diagnostic testing using information systems. He is currently evaluating the impact of guidelines on the delivery of quality of care, using electronic medical records. His work focuses on how to help clinicians make better decisions to produce more efficient, higher quality, and safer care, using information technology.

Donald A.B. Lindberg Award for Innovation in Informatics



Recognizes an individual for a specific technological, research, or educational contribution that advances biomedical informatics. The recipient's work will have been conducted in a nonprofit setting, and the adoption of the particular advance will be on a national or international level.



Carol Friedman, PhD, is a professor of Biomedical Informatics at Columbia University. Her work has demonstrated that a general natural language processing system could be used to improve clinical care and to advance understanding of medicine. Dr. Friedman developed a comprehensive natural language extraction and encoding system for the clinical domain called MedLEE, which has been in use at New York-Presbyterian Hospital, and which has been shown not only to behave similarly to medical experts but also to improve actual patient care. In collaboration, she adapted MedLEE into a natural language processing system called GENIES, which extracts biomolecular relations from journal articles to obtain data on molecular pathways. From there, she went on to co-develop the BioMedLEE system, another adaptation of MedLEE, which extracts a broad range of genotypic-phenotypic relations from the literature, and maps the extracted information to an ontology appropriate for biology. Dr. Friedman is currently working on research in the area of patient safety, using data from clinical narrative notes to detect novel adverse drug events.

Source:

Nancy Light

American Medical Informatics Association

Cell 'Anchors' Required To Prevent Muscular Dystrophy

A protein that was first identified for playing a key role in regulating normal heart rhythms also appears to be significant in helping muscle cells survive the forces of muscle contraction. The clue was a laboratory mouse that seemed to have a form of muscular dystrophy.



A group of proteins called ankyrins, or anchor proteins, were first discovered in human red blood cells by Vann Bennett, M.D. a Howard Hughes Medical Institute investigator and James B. Duke Professor of Cell Biology, Biochemistry, and Neurobiology. Ankyrins are a family of proteins that assist in attaching other proteins to the fragile cell membrane, and in the case of red blood cells, this helps cells resist shearing forces when blood is pumped vigorously throughout the body.



Bennett's team was exploring the function of anchor protein ankyrin-B (ankB) by knocking out gene expression of the gene that makes the protein. They found newborn mice missing ankB had splayed shoulder bones, which stuck out of the animals' backs like wings, rather than lying flat, a symptom of a muscular problem.



"I went back to my pediatric textbook and saw images of people with a form of muscular dystrophy who had splayed shoulder bones," said Bennett, "This opened our eyes to the possibility that, in addition to defects in controlling heart rhythm that we have studied before, the mice might also suffer from muscular dystrophy."



The team turned its attention to ankB with regard to muscle cell organization. They knew that people with Duchenne muscular dystrophy were missing the protein dystrophin, and that dystrophin is needed for a protein complex to form and protect the cells' thin plasma-membrane layer from forces exerted by muscle cells contracting.



"Without dystrophin, you lose the entire protective complex, but nobody knew why," Bennett said. "We have found the outlines of a pathway through which dystrophin assembled this complex. The missing piece of the puzzle was the ankyrin proteins." The work appears in Cell journal.



The protective layer is located at a very particular place on the muscle cell membrane, where costameres, riblike structures, hold the bundled muscle cells together. This is similar to a steel cables attaching to a specific point along a suspension bridge to distribute the forces and keep the flexible bridge intact, Bennett said.



When the protective protein layer isn't present, muscle contraction forces may break the cell membrane, toxins pour in and vital enzymes stream out. The muscle cells die.



The first experiment for the new study asked if the protein dystrophin was found on the cell plasma membrane in the study animals which lacked ankB. It was not.



Beta-dystroglycan, the core component of the dystrophin-glycoprotein complex that is responsible for attaching dystrophin to the muscle membrane, also was missing, which suggested that a loss of ankyrin-B is linked to a loss of at least two key proteins in the cell membrane, Bennett said.
















The researchers needed to continue their studies in adult mice with fully formed muscle cells to observe them in action, because muscle cells in culture don't have properly functioning costameres. They knew, however, that knocking out ankyrin-B causes the mice to die soon after birth.



Fortunately, Gai Ayalon, Ph.D., a postdoctoral fellow in the Bennett laboratory, devised a method that let researchers manipulate gene expression in a specific section of adult muscle, rather than in the whole animal. "This development let us look right away at what happened in adult mice when we produced ankyrin loss only in leg muscle," Ayalon said.



Next, they studied what happened when they turned off ankyrin-G (ankG), a different anchor protein, in muscle cells. They found that the cells needed ankG to help dystrophin and beta-dystroglycan stay in place at the costameres.



Ayalon exercised the mice to learn how the muscle cells fared without ankG. The cells tore apart.



The researchers also discovered that ankB stabilized a set of structures found in all cells, called microtubules. These structures are like tracks for the molecular motors that carry the dystrophin molecules from the site where they are made to their specific destination. Ankyrin B helps microtubules align so dystrophin molecules can travel to the membrane and then ankyrin G holds them in place, Bennett explained.



"I'm excited because ankyrin-B's ability to anchor microtubules could have broad implications in many cell types," Bennett said.







Funding sources included the Muscular Dystrophy Association and the Howard Hughes Medical Institute. Other authors included Jonathan Q. Davis and Paula B. Scotland of the Howard Hughes Medical Institute and Dr. Bennett's laboratory at Duke in Cell Biology, Biochemistry and Neurobiology.



Source: Mary Jane Gore


Duke University Medical Center

New Discovery May Aid In Creation Of Therapies For Visual, Hearing Problems

It's safe to say that cilia, the hairlike appendages jutting out from the smooth surfaces of most mammalian cells, have long been misunderstood - underestimated, even.



Not to be confused with their whiplike cousins flagella, which propel sperm, one type of cilia has been known to serve as microscopic conveyor belts. (Picture cilia reaching up like concertgoers supporting a crowd-surfer.) But for decades another type of cilia, known as "primary" cilia, was believed to serve little to no purpose. Despite the fact that almost every cell found in vertebrates has at least one primary cilium, the organ was regarded as merely an evolutionary relic - the cellular equivalent to the human appendix.



Of late, however, it has become increasingly clear that primary cilia serve as powerful communication hubs. (After all, they do sort of look like antennae.) Disruptions in the activity of cilia are now understood to lead to a whole class of diseases dubbed ciliopathies, and researchers are hustling to figure out what makes them tick.



One group of scientists in Japan last month marked a milestone in the pursuit to reveal cilia's secrets. In study results that were fast-tracked for publication and deemed a "Paper of the Week" by the Journal of Biological Chemistry, they report that they have identified a long-elusive enzyme necessary for the proper regulation of cilia.



The Hamamatsu University School of Medicine team is optimistic that the discovery may aid in the development of therapies for those with visual and hearing maladies caused by cilia dysfunction.



"Our finding might give insights into the sensory defects associated with problems in cilia function. For example, patients with some syndromes have genetic defects in cilia functions that result in retinal degeneration," explains Mitsutoshi Setou, who oversaw the team's work. "Also, age-dependent visual loss or hearing loss is known to be related to damage of the eye or ear sensory cilia. To enhance or suppress the activity of the newly found enzyme might alleviate the symptoms through the proper regulation of cilia."



With the hopes of one day manipulating cilia's activities on the perimeter of cells and, thus, how those activities affect human health, the team traced cilia's molecular roots into the depths of cells themselves.



If a cilium had a life story, it would begin with a gene. That gene encodes information during a cell's production of tubulin proteins so that they will link up into microtubules, or tiny tubes, and form the interior apparatus of a protruding cilium.



Scientists have known for some time that a group of enzymes can indirectly affect what goes on inside cilia by adding unusually branched chains of amino acids, known as glutamates, onto certain spots of the tubulin proteins that make up the microtubules. Suspecting that the addition of the amino acid chains on the tubulin building blocks might influence how material is transported within cilia, Setou's team took a closer look at how and where the chains of amino acids are added to tubulin proteins and set out to figure out what, ultimately, removed those same chains.
















To do so, they analyzed cilia on cells of sensory neurons in a living model organism, the roundworm, and studied purified protein from cultured mouse cells. Ultimately, the enzyme that strips the amino acid chains was elusive no more.



"We found out which enzyme removes part of the glutamate chain, and we now have a better understanding of that lengthening and shortening of amino acids on tubulin that regulates the function of cilia in sensory nerves," he said.



Setou is hopeful the finding will help develop therapies for a group of genetic diseases known as retinitis pigmentosa, which causes degeneration of the eye's retina and, thus, progressive loss of sight.



The human photoreceptor is a sensory neuron composed of two segments that are connected by a cilium responsible for transporting proteins from one end to the other. If that protein movement slows down or stops due to cilium malfunction, the protein accumulates abnormally and induces retinal cell death.



"Retinitis pigmentosa is one of the leading causes of adult vision loss, and yet there is no cure for it," he said. "Recent studies have shown that at least 35 genes are involved. Importantly, some of them are related to cilia formation and maintenance. This important function of cilia could be regulated by the level of polyglutamylation, which is controlled by the level of newly found enzyme."



While Setou's team focused exclusively on cilia found in sensory neurons for their experiments, the findings may prove useful in other types of cilia as well. Defective cilia lining the kidney, for example, can lead to polycystic kidney disease. Mammals rely on cilia lining reproductive organs: If there are too few functional cilia in the Fallopian tubes, which are tasked with moving a fertilized egg into proper position for growth, the ovum may hunker down too soon, causing a tubal pregnancy. Meanwhile, what are known as chemoreceptor cilia, found on olfactory neurons, detect odor.



The team's research was funded by the Japan Science and Technology Agency and the Japan Society for the Promotion of Science. The resulting "Paper of the Week" was published on the Journal of Biological Chemistry's website June 2 will appear in the July 23 issue.



The project participants included Yoshishige Kimura, Nobuya Kurabe, Koji Ikegami, Koji Tsutsumi, Yoshiyuki Konishi, Oktay Ismail Kaplan, Oliver E. Blacque, Hirofumi Kunitomo and Yuichi Iino.



Source:

Angela Hopp

American Society for Biochemistry and Molecular Biology

Rare 'Gene-For-Gene' Interaction That Helps Bacteria Kill Their Host, Discovered By Scientists

Scientists have discovered that a cousin of the plague bacterium uses a single gene to out-fox insect immune defences and kill its host.



In research published in the journal Proceedings of the National Academy of Science, scientists have found that Photorhabdus bacteria produce an antibiotic which inhibits the work of an enzyme that insects' immune systems use to defend themselves from attack.



Although such so-called gene-for-gene interactions are thought to be common in diseases, very few examples of a single gene in a pathogen targeting a single gene in an animal or human host have been identified so far.



Photorhabdus is a family of bacteria that in relatively small concentrations can kill insects - between 10-100 cells of it are typically enough - but most are harmless to humans and can be used as a biological control mechanism to replace pesticide use.



The researchers, from the universities of Bath, Bristol and Exeter, all in the UK, used the large caterpillar Manduca sexta (tobacco hornworm) to study the bacteria's so-called virulence genes.



"The beauty of this research is that we have been able to study the whole genome of the bacteria to work out how it kills its host," said Professor Stuart Reynolds from the University of Bath.



"People studying diseases think that the kind of gene-for-gene interaction between pathogen and host that we have found is quite common, but actually rather few are known, which is why this research is so interesting.



"The immune systems of all animals, even relatively simple ones like insects, are all very similar.



"This is particularly true of the innate immune system, which is the fast-acting battery of defences that recognise and kill microbes to prevent infections from occurring.



"Some remarkable discoveries have been made using insects that have subsequently allowed important advances in understanding how the human immune system works."



As part of their innate immune system, insects use an enzyme called phenoloxidase to produce reactive molecules that kill bacteria and then encapsulate them in a dense coat of black pigment called melanin.



The researchers found that Photorhabdus produces a special phenoloxidase inhibitor to protect itself against this particular defence.



They identified the inhibitor as a small molecule called 1,3-dihydroxy-2-(isopropyl)-5-(2-phenylethenyl)benzene, known as ST for short.



This molecule is also an antibiotic and Photorhabdus produces it to kill off other microbes that might grow in the corpse of the dead insect.



To test their findings, the researchers produced a mutant Photorhabdus that is unable to make ST. Without ST, the bacteria were less virulent. The researchers then used a technique known RNA interference to prevent the insects from producing the phenoloxidase enzyme. These insects were more susceptible to regular Photorhabdus bacteria.



But when the two were combined, it was found that not being able to produce ST made no difference to Photorhabdus when colonising insects unable to produce phenoloxidase.



"This is conclusive evidence for a gene-for-gene interaction between the bacterium and the insect," said Richard ffrench-Constant (correct) of Exeter University.



"Photorhabdus is an important biocontrol organism that is used to control insect pests and reduces pesticide use, so the more we know about it, the more useful it can be.



"Insects are the major players in almost every ecosystem on the planet, so we need to know as much as we can about them."







The research was supported through the Exploiting Genomics initiative funded by the Biotechnology & Biological Sciences Research Council (UK).



Source: 'An antibiotic produced by an insect-pathogenic bacterium suppresses host defenses through phenoloxidase inhibition,' Ioannis Eleftherianos, Sam Boundy, Susan A. Joyce, Shazia Aslam, James W. Marshall, Russell J. Cox, Thomas J. Simpson, David J. Clarke, Richard H. ffrench-Constant, and Stuart E. Reynolds, PNAS 2007 104: 2419-2424



Notes



The University of Bath is one of the UK's leading universities, with an international reputation for quality research and teaching. In 20 subject areas the University of Bath is rated in the top ten in the country. View a full list of the University's press releases: bath.ac.uk/pr/releases



Contact: Andrew McLaughlin


University of Bath

Nerve Structures, Or Constructs, Created In Culture: Implications For Repairing Spinal Cord Injury

Researchers at the University of Pennsylvania School of Medicine have created - in a rodent model - a completely new way to engineer nerve structures, or constructs, in culture. This proof-of-principle research has implications for eventually becoming a new method to repair spinal cord injury in humans. The work appears in the latest issue of Tissue Engineering.



"We have created a three-dimensional neural network, a mini nervous system in culture, which can be transplanted en masse," explains senior author Douglas H. Smith, MD, Professor, Department of Neurosurgery and Director of the Center for Brain Injury and Repair at Penn. Previously, Smith's group showed that they could grow axons by placing neurons from rat dorsal root ganglia (clusters of nerves just outside the spinal cord) on nutrient-filled plastic plates. Axons sprouted from the neurons on each plate and connected with neurons on the other plate. The plates were then slowly pulled apart over a series of days, aided by a precise computer-controlled motor system.



In this study, the neurons were elongated to 10mm over seven days - after which they were embedded in a collagen matrix (with growth factors), rolled into a form resembling a jelly roll, and then implanted into a rat model of spinal cord injury.



"That creates what we call a nervous-tissue construct," says Smith. "We have designed a geometrical arrangement that looks similar to the longitudinal arrangement that the spinal cord had before it was damaged. The long bundles of axons span two populations of neurons, and these neuron constructs can grow axons in two directions - toward each other and into the host spinal cord at each side. That way they can integrate and connect the 'cables' to the host tissue in order to bridge a spinal cord lesion."



After the four-week study period, the researchers found that the geometry of the construct was maintained and that the neurons at both ends and all the axons spanning these neurons survived transplantation. More importantly, the axons at the ends of the construct adjacent to the host tissue did extend through the collagen barrier, penetrating into the host tissue. Future studies will measure neuronal electrical conductivity across the newly engineered bridge and restoration of motor activity.



"The really great news - and there's still much work to be done - is that the construct survives and also integrates with host tissue," says Smith. "We find this very promising. In particular, this new technique provides a means to bridge even very long spinal lesions that are common in humans with spinal cord injury. Now we have to test whether the transplanted constructs convey a signal all the way through, and we're developing and testing a new animal model to allow us to test whether this new technique improves function."







Study co-authors are Akira Iwata, Kevin D. Browne, Bryan J. Pfister, all from Penn; and John A. Gruner, from Cephalon Inc., West Chester, PA. The research was funded by the National Institutes of Health and the Sharpe Trust.



This release and related images can be found at uphs.upenn/news/



PENN Medicine is a $2.7 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality 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 ranked #2 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 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 comprises: its flagship hospital, the Hospital of the University of Pennsylvania, consistently rated one of the nation's "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; Penn Presbyterian Medical Center; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home health care and hospice.



Contact: Karen Kreeger

karen.kreegeruphs.upenn

University of Pennsylvania School of Medicine

First Genome-wide Screen For Protein Complexes Is Completed

Today researchers in Germany announce they have finished the first complete analysis of the "molecular machines" in one of biology's most important model organisms: S. cerevisiae (baker's yeast). The study from the biotechnology company Cellzome, in collaboration with the European Molecular Biology Laboratory (EMBL), appears in this week's online edition of Nature.


"To carry out their tasks, most proteins work in dynamic complexes that may contain dozens of molecules," says Giulio Superti-Furga, who launched the large-scale project at Cellzome four years ago. "If you think of the cell as a factory floor, up to now, we've known some of the components of a fraction of the machines. That has seriously limited what we know about how cells work. This study gives us a nearly complete parts list of all the machines, and it goes beyond that to tell us how they populate the cell and partition tasks among themselves."


The study combined a method of extracting complete protein complexes from cells (tandem affinity purification, developed in 2001 by Bertrand Sйraphin at EMBL), mass spectrometry and bioinformatics to investigate the entire protein household of yeast, turning up 257 machines that had never been observed. It also revealed new components of nearly every complex already known.


In the course of the work, new computational techniques were developed at EMBL that gave new insights into the dynamic nature of protein complexes. In contrast to most man-made factories, cells continually dismantle and reassemble their machines at different stages of the cell cycle and in response to environmental challenges, such as infections.


"This would be a logistical nightmare if the cell had to build every machine from scratch any time it needed to do something," says Anne-Claude Gavin, former Director of Molecular and Cell Biology at Cellzome and currently a team leader at EMBL. "We've discovered that the reality is different. Cells use a mixed strategy of prefabricating core elements of machines and then synthesizing additional, snap-on molecules that give each machine a precise function. That provides an economic way to diversify biological processes and also to control them."


Thus if the cell needs to respond quickly, such as in a disease or another emergency, it may only need to produce few parts to switch on or tune the machine. On the other hand, if something shouldn't happen, it may only need to block the production of a few molecules.


Patrick Aloy and Rob Russell at EMBL used sophisticated computer techniques to reveal the modular organisation of these cellular machines. "This is the most complete set of protein complexes available and probably the set with the highest quality," Aloy says. "Most proteomics studies in the past have shown whether molecules interact or not, in a 'yes/no' way. The completeness of this data lets us see how likely any particular molecule is to bind to another. By combining such measurements for all the proteins in the cell, we discovered new complexes and revealed their modular nature."


"Investigating protein complexes has always posed a tricky problem - they're too small to be studied by microscopes, and generally too large to be studied by techniques like X-ray crystallography," says Russell. "But they play such a crucial role in the cell that we need to fill in this gap. There's still a huge amount to be learned from this data and from the methods we are developing to combine computational and biochemical investigations of the cell."


"This is an important milestone towards a more global and systems-wide understanding of the cells of organisms ranging from yeast to humans," says Peer Bork, Head of the Structural and Computational Biology Unit at EMBL, and one of the authors of the paper. "Ultimately we hope to achieve a 'molecular anatomy' that takes us from the level of the entire cell to the much deeper level of all the molecules and atoms that make it up."


Baker's yeast is evolutionary related to the cells of animals and humans, which means that the findings will be more widely applicable. "The same principles discovered here in yeast apply to human cells," says Gitte Neubauer, Vice President at Cellzome. "Drug targets and pathologically relevant proteins are parts of machines and pathways."


The collaboration between Cellzome and EMBL has been very successful, she says, producing fundamental new insights in how molecules are organised and contributing to Cellzome's success in complex and pathway analysis.


Anna-Lynn Wegener

wegenerembl

European Molecular Biology Laboratory

embl

Spitting Cobras Hit Their Mark

Spitting cobras have an exceptional ability to spray venom into eyes of potential attackers. A new study published in Physiological and Biochemical Zoology reveals how these snakes maximize their chances of hitting the target.



The name "spitting cobra" is a bit of a misnomer. Cobras don't actually "spit" venom, says the study's lead author Bruce Young, director of the Anatomical Laboratory in the Department of Physical Therapy at the University of Massachusetts, Lowell. Muscle contractions squeeze the cobra's venom gland, forcing venom to stream out of the snake's fangs. The muscles can produce enough pressure to spray venom up to six feet.



There are no points for distance, however. To be effective, venom must make contact with an attacker's eyes, where it causes severe pain and possibly blindness. Previous studies have found that cobras hit their targets with alarming frequency - nearly 100 percent accuracy from 60 centimeters.



Dr. Young and his colleagues, Melissa Boetig and Dr. Guido Westhoff, have found the secret to the cobra's success.



Cobra venom does not hit a victim in one spot. Instead, the venom lands in complex geometric patterns. This is no accident, according to the study. The patterns are actively produced by the cobra.



Dr. Young and his team used high-speed photography and electromyography (EMG) to detect contractions of head and neck muscles. They found that cobras engage their head and neck muscles a split second before spitting. The muscle activity rotates the head, and jerks it from side to side and back again, producing complex venom patterns.



"The venom-delivery system functions to propel the venom forward while the [head and neck] muscles produce rapid oscillations of the head that … disperse the venom, presumably maximizing the chance that a portion of the spat venom will contact the eye," the authors write.



The ability to actively disperse venom means that cobras don't need dead aim on the eye. They just need to be in the ballpark.



The paper appears in an issue of Physiological and Biochemical Zoology on the focused topic "Functional Consequences of Extreme Adaptations." PBZ is edited by Dr. James Hicks of the University of California, Irvine and published by the University of Chicago Press.







Physiological and Biochemical Zoology has presented current research in environmental, adaptational, and comparative physiology and biochemistry since 1928. The journal publishes the results of original investigations in animal physiology and biochemistry at all levels of organization, from the molecular to the organismic, focusing on adaptations to the environment.



Source: Kevin Stacey


University of Chicago Press Journals

How Small RNAs Enter Mammalian Cells

RNA interference, a natural mechanism that inhibits the gene expression of individual genes in eukaryotic cells, is a major topic in modern biology. However, their potential was usable to only a limited extent in mammals because the mechanism for the uptake of small RNAs was unknown up to now. ETH Zurich biologists have now clarified this, which also opens the door for therapies based on this mechanism.


It all started with flowers: in the nineties of the last century Norwegian researchers discovered that additional copies of a particular gene in petunias inhibited its activity instead of reinforcing it as had been assumed. A few years later it was found that the mechanism is based on the degradation of messenger RNA in the cells. Finally, in the late nineties the Nobel prizewinners Andrew Fire and Craig Mello established the technique of RNA interference, in which double-stranded RNA switches genes off efficiently and specifically. The scientists used the nematode (roundworm) Caenorhabditis elegans to study this. Subsequently, however, considerable problems arose in the attempt to transfer the strategy used by Mello and Fire to vertebrates. In particular the administration of small RNAs, known as siRNAs (small interfering RNAs), in animals proved difficult. Although it was possible to administer siRNAs successfully by using various methods such as high-pressure injections or in conjunction with cholesterol, the underlying mechanisms remained obscure. Markus Stoffel, ETH Zurich Professor at the Institute for Molecular Systems Biology, together with chemists from the Alnylam Company, has now succeeded in elucidating the mechanism for the uptake of siRNA in combination with fatty acids in mammals. The corresponding paper, which has just been published in the scientific journal "Nature Biotechnology" and will also adorn the title page of the printed version in October, represents the basis for possible siRNA therapies, among other things. This is because Stoffel showed that siRNA can be coupled effectively to various fatty acids.


Cholesterol transporters also play a part


Stoffel and his team turned to chemically modified siRNAs in combination with cholesterol, not because the method based on this compound was particularly efficient but because it had the least side-effects. First of all the researchers wanted to know whether siRNA was capable of being bonded to other lipophilic substances in addition to cholesterol, and caused a reduction in the activity of a target gene in the liver at the same time. It turned out that there are several such fatty acids. But what is it in the blood to which all these RNAs conjugated with so-called lipophilic substances bond? The ETH Zurich researchers discovered that, depending on the fatty acid used, the binding partners are the well-known cholesterol transporters High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) as well as the albumin (protein) present everywhere in the blood. Without these lipoprotein particles there is no uptake of siRNAs into the tissues, as became apparent from further experiments. In an additional experiment the scientists demonstrated that the uptake can be made considerably more efficient if the siRNA-fatty acid molecules are already firmly bonded to HDL and LDL before being administered. Stoffel's team also discovered that there is preferential uptake into different tissues depending on whether an siRNA-fatty acid molecule is bonded to HDL or LDL: all LDL compounds trigger responses in the liver, but HDL compounds also do so in the intestine or kidneys.















An irritating finding


The latter finding indicated that the uptake proceeds via HDL and LDL receptors. The researchers proved this assumption by inactivating the receptors, with the result that uptake no longer occurred. Despite the clarity of the finding, it irritated Stoffel slightly. He found it hard to imagine that the siRNAs were able to enter the cell via the normal absorption route like HDL, because this route leads into the cell's own digestive system with lysosomes that would degrade the siRNAs. So how would the siRNAs be able to avoid this degradation? Stoffel concluded that they simply use a different doorway into the cell. Thus the HDL and LDL receptors would only act as docking stations but not as an entry portal.


But what might the alternative doors be? The ETH Zurich researchers remembered that a gene product Sid1, which is necessary for the cellular uptake of siRNA, occurs in the worm Caenorhabditis elegans. The corresponding gene also has a homologue in mammals. By inactivating it, the scientists showed that it is also necessary in mammals. The overall result from all the discoveries is a mechanism for siRNA administration that starts with the bonding of siRNAs to particular fatty acids. This combination is linked to lipophilic proteins that bring about docking onto the tissue cells. The doors that allow the siRNA-fatty acid molecules to enter are then situated close to the docking station.


Prospects for new therapies and research


Stoffel thinks that through their work they were able to determine the elements that are most important for the uptake mechanism. However, he says it is very likely that yet more molecules play a part. But since an insight into the mechanism now exists for the first time, it will be possible to make specific improvements in the technique. For example Stoffel's group wants to find out whether HDL and LDL can be replaced by synthetic proteins or lipid-rich particles. He says that basically the technique has the potential to be used in gene therapy. However, the determination of the siRNA doors also opens up new approaches to fundamental research. Instead of siRNA it might also be possible to smuggle in miRNAs, another group of small RNAs, in the same way. The same mechanism ought to work for miRNA inhibitors as well. Since miRNA is increasingly "suspected" of occupying a decisive role in gene regulation in nature, its targeted administration or inhibition could yield completely new insights.

ethlife.ethz.ch

Mutation In A MiroRNA: New Cause Of Osteoporosis

Many biological processes are controlled by small molecules known as microRNAs, which work by suppressing the expression of specific sets of genes. Xiang-Hang Luo and colleagues, at Second Xiangya Hospital of Central South University, People's Republic of China, have now identified a previously unknown microRNA (miR-2861) as crucial to bone maintenance in mice and humans. Of clinical importance, expression of functional miR-2861 was absent in two related adolescents with primary osteoporosis.



Several lines of evidence determined the key role of miR-2861 in maintaining bone. First, miR-2861 promoted the in vitro development of a mouse stromal cell line into the cells responsible for bone formation. Second, in mice, in vivo silencing of miR-2861 inhibited bone formation and decreased bone mass. Last, analysis of ten patients with primary osteoporosis revealed two related adolescents in whom disease was caused by a mutation in the miR-2861 precursor (pre-miR-2861) that blocked expression of miR-2861. These data led the authors to conclude that miR-2861 has an important role in controlling the generation of the cells responsible for bone formation and that defects in the processing of its precursor can cause osteoporosis.



TITLE: A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans



Author: Xiang-Hang Luo



View this article at: jci/articles/view/39832?key=wTvdY50uyZkh8Uji59Po



Source: Karen Honey


Journal of Clinical Investigation

Desert Soil Bacteria More Diverse Than Amazon Soil Bacteria

Ironically, in the diversity of soil bacteria, the otherwise species-rich Amazon is a more like a desert, while the arid desert is a teeming microbial Amazon, researchers have found. Their first-ever continental-scale genetic survey of soil bacteria revealed that the primary factor that seems to govern the diversity of soil bacteria is soil pH. Thus, the acidic soils of topical forests harbor fewer bacterial species than the neutral soils of deserts.


The researchers said that, since soil bacteria play a fundamental role in a vast array of ecological processes, their survey constitutes an initial step in a new research pathway to understanding that role.


Biologists Noah Fierer and Robert Jackson published their findings in the Early Online Edition of the Proceedings of the National Academy of Sciences the week of Jan. 9, 2006. Their work was sponsored by the National Science Foundation and the Mellon Foundation. Fierer, a former post-doctoral scientist at Duke University, is at the University of Colorado; and Jackson is in the Department of Biology and the Nicholas School of the Environment and Earth Sciences at Duke.


"Although soil bacteria have been studied for centuries, fundamental biological questions remain unanswered," said Fierer. "We probably know more about the organisms in the deepest ocean trenches than we know about the organisms living in soil in our backyards.


"We step on soil every day, but few people realize that 'dirt' supports a complex community of microorganisms that plays a critical role on Earth, he said. "The number of bacterial species in a spoonful of soil is likely to exceed the total number of plant species in all of the United States."


According to Jackson, "Microbes are very important for most of the critical processes in nature. They are extremely important for the cycles that make nutrients available to plants and animals; and for much of the respiration that returns carbon back to the atmosphere as carbon dioxide. They also give off most of the important trace gases in our atmosphere like methane.


"Given this importance, it was really surprising to us that no one had tried to systematically explore the pattern of diversity of soil bacteria on a continent-wide scale. Part of the reason is such a survey is technologically challenging, and it's logistically challenging as well," he said.


In their survey, Fierer and Jackson collected 98 soil samples from across North and South America. They chose research sites in which considerable scientific data had already been collected that would enable them to assess the role of factors such as temperature and rainfall on diversity. These included many of the Long-Term Ecological Reserves in North America, supported by the National Science Foundation. While some of the samples were provided by scientists conducting studies in such research areas, other samples required remote treks through the Amazonian jungle, said Jackson.















The researchers assessed the microbial species diversity of their samples by performing "DNA fingerprinting" that would reveal the diversity of a particular kind of DNA called ribosomal DNA. This DNA is known to differ considerably among bacterial species, serving as a type of genetic "bar code" that can be used to differentiate species. While the measure did not tell the researchers how many microbial species existed in the samples, it did give them a comparative measure of such diversity among the samples, said Jackson. The analyses revealed large differences among the samples in terms of diversity. The scientists then correlated that diversity with environmental factors, including latitude, temperature and soil pH.


"As biologists and ecologists, the factors that we think of typically as controlling plant and animal diversity didn't seem to correlate with the diversity of microbes," said Jackson. "Instead, the factor that correlated best with diversity was the pH of the soil they were growing in. It does make sense, since every biologist knows that when you culture microorganisms in the laboratory, the diversity and the health of those organisms tends to decrease in more extreme pHs." However, Jackson did not rule out the possibility of microbial "hot spots" that their broad survey might have missed.


Added Fierer, "These findings also suggest that soils with similar levels of acidity, even if those soils are thousands of miles apart, have similar bacterial communities."


Jackson emphasized that "This is really just a first step to a better understanding of what controls microbial diversity around the world. Such understanding will offer important insights into the many processes soil microorganisms control -- including the carbon cycle of decomposition of organic matter and the nitrogen-fixing cycle -- both of which free nutrients for plants. Also, microbes control emissions of methane and other gases, many of which are important greenhouse gases," he said.


Dennis Meredith

dennis.meredithduke

Duke University

duke

Why Do People With Down Syndrome Have Less Cancer?

Most cancers are rare in people with Down syndrome, whose overall cancer mortality is below 10 percent of that in the general population. Since they have an extra copy of chromosome 21, it's been proposed that people with Down syndrome may be getting an extra dose of one or more cancer-protective genes. The late cancer researcher Judah Folkman, MD, founder of the Vascular Biology Program at Children's Hospital Boston, popularized the notion that they might be benefiting from a gene that blocks angiogenesis, the development of blood vessels essential for cancer's growth, since their incidence of other angiogenesis-related diseases like macular degeneration is also lower. A study from Children's confirms this idea in mice and human cells and identifies specific new therapeutic targets for treating cancer.


Publishing online May 20 in the journal Nature, cancer researcher Sandra Ryeom, PhD, and colleagues from Children's Vascular Biology Program show that a single extra copy of Dscr1 (one of the 231 genes on chromosome 21 affected by trisomy, with three copies rather than two) is sufficient to significantly suppress angiogenesis and tumor growth in mice, as well as angiogenesis in human cells. The team also found its protein, DSCR1, to be elevated in tissues from people with Down syndrome and in a mouse model of the disease.


Further study confirmed that DSCR1 acts by suppressing signaling by the angiogenesis-promoting protein vascular endothelial growth factor (VEGF). In a mouse model of Down syndrome, endothelial cells (which make up blood vessel walls) showed a decreased growth response to VEGF when they had an extra copy of Dscr1. An extra copy of another chromosome 21 gene, Dyrk1A, also appeared to decrease cells' response to VEGF.


Finally, Ryeom and colleagues showed that these extra genes suppress VEGF signaling via a specific signaling pathway inside endothelial cells -- the calcineurin pathway. Until now, Ryeom says, little has been known about the internal pathways VEGF activates once it binds to cellular receptors; most existing anti-VEGF drugs work by simply binding to VEGF (like Avastin) or blocking its ability to bind to its cellular receptors.


"We're now moving further downstream by going inside the cell," Ryeom says. "When we targeted calcineurin, we suppressed the ability of endothelial cells to grow and form vessels. While it's likely not the only pathway that's involved, if you take it out, VEGF is only half as effective."


Ryeom and her group next validated the mouse findings in human cells. In collaboration with George Daley, MD, PhD, and colleagues in the Stem Cell program at Children's, she worked with induced pluripotent stem cells (iPS cells) created from skin cells from a patient with Down syndrome -- one of 10 disease-specific lines recently developed in Daley's lab.















Knowing that iPS cells tend to induce tumors known as teratomas when inserted into mice, Ryeom guessed that teratomas grown from iPS cells with an extra chromosome 21 would have far fewer blood vessels than teratomas from iPS cells with the normal number of chromosomes. She was right: blood vessels budded in the Down teratomas, but never fully formed.


"The studies in the iPS cells helped validate and confirm that the suppression of angiogenesis that we saw in mouse models also holds true in humans," says Ryeom. "It suggests that these two genes might point to a viable cancer therapy."


Ryeom's group has identified which part of the DSCR1 protein blocks calcineurin and is testing to see whether that fragment can be delivered specifically to endothelial cells, to prevent them from forming new blood vessels, without affecting calcineurin pathways in other cells and causing side effects. "Immunosuppressive drugs also target calcineurin in T-cells," Ryeom notes. "We think that Dscr1 blocks calcineurin specifically in endothelial cells, without affecting T-cells, but we need to check."


Folkman's interest in why patients with Down syndrome have such a reduced risk for cancer focused on endostatin, an anti-angiogenic compound made by the body. Discovered in the Folkman lab, endostatin is a fragment of collagen 18 -- whose gene is also on chromosome 21. People with Down syndrome reportedly have almost doubled levels of endostatin because of the extra copy of the gene.


"I think there may be four or five genes on chromosome 21 that are necessary for angiogenesis suppression," says Ryeom. "In huge databases of cancer patients with solid tumors, there are very few with Down syndrome. This suggests that protection from chromosome 21 genes is pretty complete."


The study was funded by the Howard Hughes Medical Institute, the Harvard Stem Cell Institute and the NIH Director's Pioneer Award (supporting George Daley, MD, PhD); as well as the Smith Family Medical Foundation, the Garrett B. Smith Foundation and Annie's Fun Foundation (supporting Sandra Ryeom, PhD). Kwan-Hyuck Baek, PhD, of Children's Vascular Biology program was the paper's first author.


Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School.


Source: Children's Hospital Boston


View drug information on Avastin.

In Pre-Clinical Tests Drug Inhibits Neuroblastoma Blood Supply

Researchers from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have found a way to prevent blood vessels from aiding the growth of neuroblastoma, a childhood cancer. The pre-clinical study was presented n a platform session at the 22nd annual meeting of the American Society of Pediatric Hematology/Oncology.



Investigators at the Children's Cancer Hospital at M. D. Anderson have discovered that the drug, AMD3100, hinders the formation of tumor blood vessels and reduces human neuroblastoma tumor growth by more than 75 percent in mice.



The drug blocks interaction between SDF-1a and its receptor CXCR4. This pathway plays an important role in signaling cells to different areas of the body. More specifically, the study suggests that SDF-1a plays a role in differentiating and/or attracting pericyte-like cells to neuroblastoma tumors.



Pericytes are essential for organizing blood vessels to feed tumors. Without pericytes, blood vessels are dysfunctional and tumors are left without a vital blood source. This study found that AMD3100 decreased the number of pericyte-like cells in neuroblastoma tumors by close to 90 percent.



"AMD3100 works by shutting down the process that tumors need to set up vascular systems," says Patrick Zweidler-McKay, M.D., Ph.D., assistant professor at the Children's Cancer Hospital and senior investigator on the study. "The drug doesn't kill neuroblastoma cells directly, but it prevents tumors from growing rapidly by disrupting their blood supply."



In tissue culture, investigators were also able to show how AMD3100 prevented neuroblastoma cells from migrating toward SDF-1a ligands. SDF-1a is present at high levels in the bone marrow, one of two areas where neuroblastoma most commonly metastasizes.



"There is the possibility that this therapy could help prevent neuroblastoma metastasis to the bone marrow. However, more studies are needed to investigate this theory," says Zweidler-McKay.



According to the American Cancer Society, approximately 650 children, mainly under the age of five, are diagnosed with neuroblastoma in the United States each year. Close to two-thirds of these children are diagnosed after the cancer has metastasized to other parts of the body. For these patients with high-risk neuroblastoma, long-term survival is less than 40 percent because the tumors are often resistant to traditional chemotherapy.



Other investigators on the study were Alejandro Levy, M.D., Lindsey Nunnally, Lizhi Zeng, M.D., Wendy Fang, M.D., Keri Schadler, Riitta Nolo, Ph.D., and Peter Zage, M.D., Ph.D.



Source:
Lindsay Anderson


University of Texas M. D. Anderson Cancer Center

Experimental Agents May Prevent Radiation-Induced Leukemia

Treatment with biphosphonates could prevent radiation-induced leukemia, according to data presented at the American Association for Cancer Research 100th Annual Meeting 2009.



Alexandra Miller, Ph.D., a senior scientist at the Armed Forces Radiobiology Research Institute, said her research is designed to help military and space agency personnel, who are more likely to be exposed to risky levels of radiation than the general population. However, she said the research could have applications for civilian populations as well.



"It is possible, although not yet proven, that the compound we studied could have a general effect on leukemia associated with causes other than radiation, such as age, which is much more common," said Miller.



The compounds Miller studied are biphosphonates known to scientists as ethane-1-hydroxy-1, 1-biphosphonate (EHBP) and carballylic amido bis phosphonic acid (CAPBP). Biphosphonates have emerged as an attractive chemopreventive agent due to earlier research that suggests they prevent bone metastasis and because they have an ability to remove uranium from the body.



For the current study, Miller and her colleagues irradiated laboratory mice at 3.5 Gy; all of the mice who were not treated with either EHBP or CAPBP developed leukemia.



By contrast, if they were treated with six doses of EHBP only 75 percent of mice developed leukemia. Similarly, only 65 percent of mice treated with CAPBP developed leukemia.



Source:
Jeremy Moore


American Association for Cancer Research

Boston Hosts AAAS And Fulbright Academy Meetings

Singapore's focused transformation into a scientific powerhouse in the biomedical sciences and physical sciences and engineering will stage a presence this week in Boston at the annual meetings of the American Association for the Advancement of Sciences (AAAS) and the Fulbright Academy of Science and Technology.



At the AAAS conference, Singapore scientists will speak at a Friday morning, Feb. 15th symposium on the continuum of cancer research, from the laboratory through clinical and translational research studies with patients.



That afternoon at the Fulbright Academy conference, an expert on Singapore's educational system will speak about the school programs that contribute to Singapore pupils' top ranking internationally in science and math.



The Asian city-state's scientific and educational initiatives under A*STAR (Agency for Science, Technology and Research), established in 2000, will also be showcased at the AAAS meeting. It will highlight Singapore's public sector research program, which spans 14 research institutes and several scientific consortia and extramural research with the country's universities, hospital research centres and other local and international partners.



"By participating in the AAAS and the Fulbright Academy annual meetings, we want to strengthen our networks with the international research community to bring about breakthroughs to benefit society. At the same time, this is an excellent opportunity for Singapore to share our experiences in pioneering new directions in scientific education and R&D," said A*STAR Chairman Lim Chuan Poh, who will speak at the Fulbright meeting.



To strengthen Singapore's capabilities in the sciences, A*STAR has turned for advice to many of the world's leaders of science including Nobel laureate and AAAS President David Baltimore. In addition, many other scientists have been recruited to Singapore, full or part-time, to establish new research programs or expand existing ones.



Two such transplanted scientists - Edison Liu, M.D., and Nancy Jenkins, Ph.D. - will join Singapore's internationally respected oncologist and clinical researcher, John Wong, M.D., as speakers in the Friday morning AAAS symposium. They are among the 3,200 scientists from 50 countries who work in A*STAR research institutes.



During the past seven years, A*STAR has built from scratch a biomedical research hub - called Biopolis - to headquarter the new and expanded research programs in genomics, molecular and cell biology, bioengineering and nanotechnology, medical biology, and clinical and translational research.



A*STAR's complementary research programs in infocomm and media, high performance computing, manufacturing, microelectronics, data storage, and chemical and materials science will soon be moving into Fusionopolis, a physical sciences and engineering research hub, when it opens in October 2008.
















While the new laboratories at Biopolis and Fusionopolis were designed for 21st century science, Mr. Lim stressed, "More important than the physical infrastructure is talented scientists who are passionate about good science and impactful research, and we have a pool of some of the best international leaders of science who share this passion."



He also pointed out that a dynamic culture of collaboration characterizes A*STAR's research, between public sector and corporate R&D labs as well as across scientific disciplines.



"Such private-public partnerships and multi-disciplinary research among physical sciences and biomedical sciences accelerate the development of ideas from 'lab' to 'life,'" he explained.



"The various research supported by A*STAR includes both investigator-initiated studies as well as directed research built around strategic thematic areas that impact the health, lifestyles or economy of Singaporeans and the available or potential research strengths that we have in those areas," said Mr. Lim.



To spur talented Singaporean students' interest for careers in science, A*STAR supports a science education program that encompasses public schools as well as college and university degree studies. Before he became A*STAR Chairman last year, Mr. Lim was Permanent Secretary in the Singapore Ministry of Education.



In his Fulbright Academy lecture, Mr. Lim will review the educational system that has resulted in Singapore fourth and eighth grade students' ranking #1 in science and math. He also will describe the A*STAR scholarship programs that today support the Ph.D. degree educations of over 700 young Singaporeans. "Many of these students, we hope, will be the future leaders of science and technology in Singapore," he noted.



Said Mr. Eric Howard, Executive Director of the Fulbright Academy of Science & Technology, "A*STAR is a valuable strategic partner to us in reaching out to the international scientific community. We are a network of Fulbright scholars and alumni, so our ideals are closely aligned in our desire to promote advancement through dialogues in science and technology. Mr Lim's talk at the Academy's Annual Conference will address many relevant issues in the areas of science and math education and we are confident that our delegates will greatly benefit from the session."



The Fulbright Academy is partnering A*STAR to launch its inaugural Asian conference in October focusing on the future of cities. A growing portion of humanity is moving to cities, so this conference will examine the efforts of Singapore and other cities to build safe, conducive and productive urban areas.



At the meeting, Fulbright scholars, key leaders and innovative researchers from around the world will exchange ideas on scientific and technological solutions for sustainable cities of the future.



At this year's AAAS conference, in support of nurturing young aspiring talent, A*STAR will sponsor the competition that recognizes college and university students who present at the meeting the best poster displays about research.



During the meeting, A*STAR will also announce its third call for the A*STAR Investigatorship programme which offers promising young postdocs from around the world to do independent research at A*STAR, as well as its new visiting "science writer-in-residence" program that will bring experienced science journalists to the island-state to meet with journalists as well as industry leaders, scientists and students.







About Agency for Science, Technology and Research (A*STAR)



A*STAR is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 14 research institutes and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The Agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.a-star.sg/



Source: Cathy Yarbrough


Agency for Science, Technology and Research (A*STAR), Singapore

New Insights Into Novel Mechanisms Of Action Of Genmab's HuMax-EGFr

Genmab A/S
(CSE: GEN) announced today new insights into the novel mechanisms of action
of its antibody HuMax-EGFr(TM) (zalutumumab). By using Protein
Tomography(TM), a relatively new technology which uses an electron
microscope to view the three dimensional structure of proteins on the
surface of cells, HuMax-EGFr was shown to lock the EGF receptor in an
inactive conformation which prevents receptor activation and the binding of
growth factors. Furthermore, HuMax- EGFr was shown to inhibit EGF receptor
signaling by preventing receptor dimerization, the pairing of two receptor
molecules which starts the signaling cascade. All of these mechanisms have
the potential to interfere with cancer cell growth.


"Coupled with previous findings that HuMax-EGFr is able to induce
potent ADCC and block growth factor binding to EGF receptors, these studies
have given us greater insight into the novel way HuMax-EGFr works," said
Lisa N. Drakeman, Ph.D., Chief Executive Officer of Genmab.



These data will be presented by Genmab and Sidec Technologies AB, at
the 3rd Novel Solution Seminar for Drug Creation and Development in Tokyo,
Japan on March 12 and in Osaka, Japan on March 14, 2007.



About Genmab A/S



Genmab A/S is a biotechnology company that creates and develops human
antibodies for the treatment of life-threatening and debilitating diseases.
Genmab has numerous products in development to treat cancer, infectious
disease, rheumatoid arthritis and other inflammatory conditions, and
intends to continue assembling a broad portfolio of new therapeutic
products. At present, Genmab has multiple partnerships to gain access to
disease targets and develop novel human antibodies including agreements
with Roche and Amgen. A broad alliance provides Genmab with access to
Medarex, Inc.'s array of proprietary technologies, including the UltiMAb(R)
platform for the rapid creation and development of human antibodies to
virtually any disease target. In addition, Genmab has developed
UniBody(TM), a new proprietary technology that creates a stable, smaller
antibody format. Genmab has operations in Europe and the US. For more
information about Genmab, visit genmab.




This press release contains forward looking statements. The words
"believe", "expect", "anticipate", "intend" and "plan" and similar
expressions identify forward looking statements. Actual results or
performance may differ materially from any future results or performance
expressed or implied by such statements. The important factors that could
cause our actual results or performance to differ materially include, among
others, risks associated with product discovery and development,
uncertainties related to the outcome and conduct of clinical trials
including unforeseen safety issues, uncertainties related to product
manufacturing, the lack of market acceptance of our products, our inability
to manage growth, the competitive environment in relation to our business
area and markets, our inability to attract and retain suitably qualified
personnel, the unenforceability or lack of protection of our patents and
proprietary rights, our relationships with affiliated entities, changes and
developments in technology which may render our products obsolete, and
other factors. Genmab is not under an obligation to up-date statements
regarding the future following the publication of this release; nor to
confirm such statements in relation to actual results, unless this is
required by law.



Genmab(R); the Y-shaped Genmab logo(R); HuMax(R); HuMax-CD4(R); HuMax-
EGFr(TM); HuMax-Inflam(TM); HuMax-CD20(TM); HuMax-TAC(TM); HuMax-HepC(TM),
HuMax-CD38(TM); HuMax-ZP3(TM); and UniBody(TM) are all trademarks of Genmab
A/S.



UltiMAb(R) is a trademark of Medarex, Inc.


Genmab

genmab

Mechanics Of Bacteria Colonies Measured By New Lab-On-A-Chip

Researchers at the University of Michigan have devised a microscale tool to help them understand the mechanical behavior of biofilms, slimy colonies of bacteria involved in most human infectious diseases.



Most bacteria in nature take the form of biofilms. Bacteria are single-celled organisms, but they rarely live alone, said John Younger, associate chair for research in the Department of Emergency Medicine at the U-M Health System. Younger is a co-author of a paper about the research that will be the cover story of the July 7 edition of Langmuir.



The new tool is a microfluidic device, also known as a "lab-on-a-chip." Representing a new application of microfluidics, the device measures biofilms' resistance to pressure. Biofilms experience various kinds of pressure in nature and in the body as they squeeze through capillaries and adhere to the surfaces of medical devices, for example.



"If you want to understand biofilms and their life cycle, you need to consider their genetics, but also their mechanical properties. You need to think of biofilms as materials that respond to forces, because how they live in the environment depends on that response," said Mike Solomon, associate professor of chemical engineering and macromolecular science and engineering, who is senior author of the paper.



Mechanical forces are at play when our bodies defend against these bacterial colonies as well, Younger says.



"We think a lot of host defense boils down to doing some kind of physical work on these materials, from commonplace events like hand-washing and coughing to more mysterious processes like removing them out of the bloodstream during a serious infection," he said. "You can study gene expression patterns as much as you want, but until you know when the materials will bend or break, you don't really know what the immune system has to do from a physical perspective to fight this opponent."



Researchers haven't studied these properties yet because there hasn't been a good way to examine biofilms at the appropriate scale.



The U-M microfluidic device provides the right scale. The channel-etched chip, made from a flexible polymer, allows researchers to study minute samples of between 50 and 500 bacterial cells that form biofilms of 10-50 microns in size. A micron is one-millionth of a meter. A human hair is about 100 microns wide.



Such small samples behave in the device as they do in the body. Tools that require larger samples don't always give an accurate picture of how a particular substance behaves on the smallest scales.



The researchers found that the biofilms they studied had a greater elasticity than previous methods had measured. They also discovered a "strain hardening response," which means that the more pressure they applied to the biofilms, the more resistance the materials put forth.



If doctors and engineers can gain a greater understanding of how biofilms behave, they could perhaps design medical equipment that is more difficult for the bacteria to adhere to, Younger said.



The experiments were performed on colonies of Staphylococcus epidermidis and Klebsiella pneumoniae, which are known to cause infections in hospitals.



The new microfluidic device could also be used to measure the resistance of various other soft-solid materials in the consumer products, food science, biomaterials and pharmaceutical fields.



Notes:

The paper is called, "Flexible Microfluidic Device for Mechanical Property Characterization of Soft Viscoelastic Solids Such as Bacterial Biofilms." The first author is Danial Hohne, a recently-graduated Ph.D. student in the Department of Chemical Engineering. The research is funded by the National Institutes of Health, the National Institute of General Medical Sciences, the U-M Center for Computational Medicine and Biology and the Department of Emergency Medicine.



Source:
Nicole Casal Moore


University of Michigan

Euroscreen Receives Key US Patent Covering Screening Methods Using Human P2Y11 Purinergic Receptor

Euroscreen SA announced that it was awarded a US patent that covers the use of a G-Protein-Coupled Receptor (GPCR) known as the human P2Y11 receptor. The new Euroscreen's US patent (7,264,940) protects screening methods to single out compounds that modulate, either up or down, the biological activity of the P2Y11 receptor.


The P2Y11 receptor was cloned and characterized in collaboration with the UniversitГ© Libre de Bruxelles. The group of Professor Jean-Marie Boeynaems has shown that the activation of the P2Y11 receptor leads to the differentiation of human promyelocytic leukemia cells into neutrophil-like cells, suggesting that P2Y11 agonists might be used for the treatment of some forms of leukemia. In addition, its role in neutrophil maturation makes it a potential target for the treatment of neutropenia.


Commenting on the announcement, Jean Combalbert, Chief executive Officer of Euroscreen, said: "This new US patent in the field of purinergic receptors represents an additional stone to our growing portfolio. It will enable Euroscreen to generate revenues from companies wishing to use the human P2Y11 receptor as target for innovative drugs, through licence fees and milestones in the short term, and royalties on sales of any products generated in the longer term."


This new patent is extending the P2Y11 patent family, Euroscreen having already obtained a similar European patent and awaiting the issuance of equivalent patent applications in Japan and Canada, whose pending claims relate to similar subject matter.


About Euroscreen SA


Euroscreen, a privately held company based in Brussels, Belgium, is a preclinical-stage biopharmaceutical company focusing on the discovery, development and partnering of small molecule drugs for unmet medical needs. Euroscreen is developing a pipeline of compounds targeting G Protein-Coupled Receptors (GPCRs) using over 12 years of experience in research and commercialization of this critical class of drug targets. Initially, Euroscreen was a spin-off company of the "UniversitГ© Libre de Bruxelles" based on GPCRs reagents development and commercialization. Euroscreen is now developing drugs on internal targets such as CCR5 and multiple additional targets as well as several preclinical-stage collaborations with partners.


The Company has developed a broad target portfolio for licensing to biopharmaceutical companies. Such patents address GPCRs such as CCR5, Chemerin receptor, GPR43, GPR7/8, FPRL2, purinergic receptors (P2Y4, P2Y11 and P2Y13) and SHIP2 for type II diabetes. Euroscreen is able to offer intellectual property rights to companies for the development of therapeutic drugs that act through these targets.


Euroscreen pursues a dual platform strategy of combining its internal drug discovery programs with its fully dedicated Custom Screening Business Unit (EuroSCREEN FAST), providing GPCR customized screening, GPCR antibody development and other services to serve biotech and pharmaceutical companies around the world. The company has research and licensing partnerships with Alchemia, Boehringer Ingelheim, Cephalon, GNF, HGS, ICOS, Medarex, Novartis and Pfizer.

euroscreen

Fundamental Discovery By Einstein Researchers Reveals How Fat Is Stored In Cells

In discovering the genes responsible for storing fat in cells, scientists at the Albert
Einstein College of Medicine of Yeshiva University have answered one of biology's most fundamental
questions. Their findings, which appear in the December 17 to 21 "Early Edition" online issue of the
Proceedings of the National Academy of Sciences, could lead to new strategies for treating obesity and
the diseases associated with it.


Scientists had previously identified the genes responsible for synthesizing fat within cells. But
the genes governing the next step--packaging the fat inside a layer of phospholipids and proteins to form
lipid droplets-have long been sought, and for good reason.


"Storing fat in lipid droplets appears crucially important for enabling cells to use fat as an energy
source," says Dr. David Silver, assistant professor of biochemistry at Einstein and senior author of the
article. "From yeast to humans, partitioning fat into droplets is a universal feature among animals. And
in humans, of course, acquiring excessive amounts of these fat droplets in our fat tissue leads to
obesity." [See photomicrograph of lipid droplets in fat cells at end of press release].


Dr. Silver and his colleagues identified two genes that are crucial for packaging fat into lipid
droplets. They called the genes FIT1 and FIT2 (for Fat-Inducing Transcripts 1 and 2). Both genes
code for proteins that are more than 200 amino acids in length, and the two genes are 50
percent similar to each other. The amino acid sequences of the FIT proteins do not
resemble any other known proteins found in any species, indicating that the FIT genes
comprise a novel gene family.


The researchers conducted several different experiments to confirm the roles of
FIT1 and FIT2 in fat storage. In one experiment, they overexpressed both FIT1 and FIT2
genes (i.e., inserted extra copies of them) in human cells. While the rate of fat synthesis
stayed the same in both "overexpressed" and control cells, the number of lipid droplets in
the "overexpressed" cells increased dramatically, between four- and six-fold.


Using a different tactic to evaluate FIT function, the researchers next "knocked
down" FIT2 in mouse fat cells (FIT1 is not expressed in these cells). Their reasoning: If
FIT2 is indeed essential for lipid droplet formation, then suppressing FIT2 expression
should abolish lipid-droplet accumulation. Examination of these fat cells for lipid
droplets revealed that cells with suppressed FIT2 expression had a drastic reduction in
lipid droplets.


Finally, the researchers carried out a similar FIT2 "knock down" experiment in a
whole animal-the zebrafish. Zebrafish eggs were injected with a segment of DNA
designed to interfere with FIT2 expression. Then, to induce lipid droplet formation in
zebrafish larvae (where it is localized mainly in the liver and intestine), free-swimming
six-day-old larvae were fed a high-fat diet for six hours. Although the larvae had
exhibited normal feeding behavior, examination of their livers and intestines revealed a
near-absence of lipid droplets.


"These lines of evidence supported our conclusion that FIT genes are necessary
for the accumulation of lipid droplets in cells," says Dr. Silver. "Now that we've
identified the genes and the proteins they code for, it should be possible to develop drugs
that can regulate their expression or activity. Such drugs could prove extremely valuable,
not only for treating the main result of excess lipid droplet accumulation-obesity-but
for alleviating the serious disorders that arise from obesity including type 2 diabetes and
heart disease."


Other Einstein scientists involved in the research were lead author Bert Kadereit,
Pradeep Kumar, Wen-Jun Wang, Diego Miranda, Erik L. Snapp, Nadia Severina, Ingrid
Torregroza and Todd Evans.

Albert Einstein College of Medicine

Northeastern And MIT Make Key Observation About Animal Behavior Patterns

Northeastern University and MIT researchers have observed-for the first time-the origin of a mass gathering and the subsequent migration of hundreds of millions of animals. Utilizing a new imaging technology invented by the researchers, they were able to instantaneously image and continuously monitor entire shoals of fish containing hundreds of millions of individuals stretching for tens of kilometers off Georges Bank near Boston.


They found that once large shoals of Atlantic herring reach a critical population density, a "chain reaction" triggers the synchronized movement of millions of individual fish over a large area. The phenomenon is akin to a human "wave" moving in a sports stadium. They also observed that the fish "commute" to the shallower waters of the bank, where they spawn in the darkness, then return to deeper water and disband the following morning.


The findings, published in the latest issue of Science, confirm general theories about the behavior of large groups of animals that, until now, had not been verified in nature. Previously, these theories for diverse animal groups, ranging from flocks of birds to swarms of locusts, had only been tested with computer simulations and laboratory experiments.


"As far as we know, this is the first time we've quantified this behavior in nature and over such a huge ecosystem," said Nicholas C. Makris, professor of mechanical and ocean engineering at MIT, who co-led this project with Northeastern professor Purnima Ratilal.



As part of the project, two research vessels were equipped with Ocean Acoustic Waveguide Remote Sensing (OAWRS) technology, developed by professors Makris and Ratilal. Both OAWRS and conventional sensing methods depend on acoustics to locate objects by bouncing sound waves off of them. OAWRS, however, captures images of a 100 kilometer diameter area every 75 seconds, providing far more complete coverage of fish population and behavior than conventional methods. In addition, OAWRS does so at a lower frequency than conventional methods, which allows the sound to travel much greater distances with lower intensity and still provide useful information.


"After analyzing the data carefully during the initial days at sea, I noticed what seemed to be a daily pattern of fish shoal formation," said Ratilal, assistant professor of electrical and computer engineering at Northeastern. "When I predicted what would happen the following day, and it turned out to be right, we knew we had discovered something really important."


Makris and Ratilal see potential in using OAWRS to better monitor-and conserve-fish populations. Large oceanic fish shoals provide vital links in the ocean and human food chain, they explained, but their sheer size makes it difficult to collect information using conventional methods.


Northeastern PhD. students Mark Andrews and Zheng Gong contributed to this research. Additional collaborators include J. Michael Jech of the Northeast Fisheries Science Center, Olav Rune Godoe of the Institute of Marine Research in Norway, as well as others from MIT, Northeastern and the Southeast Fisheries Science Center. The project was sponsored by the National Oceanographic Partnership Program, the Office of Naval Research and the Alfred P. Sloan Foundation, and is a contribution to the Census of Marine Life.

Source
Northeastern University

FSU Scientific Computing Department Hosts International Conference

Researchers from all over the world will gather at Florida State University for a major international conference that focuses on predicting the properties of materials and finding new ways to improve these properties.


More than 500 materials science scholars and professionals will exchange research findings related to complex materials problems and development of innovative theoretical and computational concepts, and they will address issues of importance to practical applications of "multiscale materials modeling" at the conference dubbed MMM2008, which will be held Oct. 27-31 at the Tallahassee/Leon County Civic Center.


FSU's new Department of Scientific Computing, formerly the School of Computational Science, is hosting the event after Professor Anter El-Azab led the team that presented the winning proposal at the conference's previous meeting in Germany two years ago. El-Azab, who directs a materials modeling and simulation lab at FSU, is the conference chair.



"To be chosen to host a meeting such as this one, an organization and its people have to have a worldwide reputation in the subject matter," said Max Gunzburger, chair of the Department of Scientific Computing. "This is recognition by the international research community of FSU's strength in materials science and Professor El-Azab's reputation as a leader in that community."


In a world where new technologies and products depend on the use of materials that are lighter, stronger, smaller and more flexible, scientists must be able to predict how different materials, including metals, glasses, ceramics and various composites, act under different conditions, at both the atomic or molecular level and at the macroscopic level; in other words, multiscale.


"If one wants to use a material in, say, a jet engine, how the material reacts to high temperature and mechanical forces may depend on what is happening at the molecular level," Gunzburger explained. "Thus, one has to know the material response at lengths ranging from the size of the engine component down to intermolecular distances."


Increasingly, scientists are modeling the behavior of materials in different environments by using sophisticated mathematical and computational algorithms. This development has attracted mathematicians and computational scientists to the multiscale materials modeling field, which is a new science and engineering frontier that transcends the boundaries between the traditional disciplines of mechanics, physics and chemistry of materials.


"The increasing interest in this field by mathematicians and computational scientists is creating opportunities for solving computational problems in the field with an unprecedented level of rigor and accuracy," El-Azab said.


Computational algorithms are especially emphasized in this year's conference program, "Tackling Materials Complexities via Computational Science," which is inspired by the research mission of FSU's newly created Department of Scientific Computing.


The conference includes symposia with focus areas in statistical models of materials, mechanics of materials across scales, computational materials design and biological and soft matter response, as well as the response of materials under extreme conditions in the nuclear reactor environment.


FSU Francis Eppes Professor of Chemistry and Biochemistry Harold Kroto, who won a Nobel Prize in 1996 for his co-discovery of "buckyballs," will give the opening plenary on "Architecture in Nanospace" at 9 a.m. Oct 27.


Other speakers making presentations throughout the conference include Nasr Ghoniem, University of California Distinguished Professor at the University of California, Los Angeles; Subra Suresh, the Ford Professor and Dean of the School of Engineering at Massachusetts Institute of Technology; Stephane Roux, a professor at Ecole Normale Superieure de Cachan; and Bennett C. Larson, a corporate fellow at Oak Ridge National Laboratory.


For more information about the conference, visit MMM2008.

CSH Protocols Features Methods For Studying DNA Repair And Protein Modification

This month's issue of Cold Spring Harbor Protocols (cshprotocols/TOCs/toc1_09.dtl) features two articles detailing experimental methods for the analysis of molecular processes involved in DNA repair and post-translational modification of proteins.



Homologous recombination is an important mechanism for the repair of damaged chromosomes. When this occurs, a Displacement Loop, or "D-loop," is formed as the two strands of the DNA molecule are separated and held apart by a third strand of DNA. Patrick Sung's laboratory at Yale University (info.med.yale/mbb/sung/) has detailed a method for generating these structures in their article, "Assay for Human Rad51-Mediated DNA Displacement Loop Formation." This reconstituted system provides researchers a biochemical means to dissect the mechanisms of the homologous recombination machinery. The protocol is freely accessible on the website for Cold Spring Harbor Protocols (cshprotocols/cgi/content/full/2009/1/pdb.prot5120).



Sumoylation involves the attachment of Small Ubiquitin-like Modifier or "SUMO" proteins to other proteins in a cell. Sumoylation modifies these target proteins and can affect a variety of activities, including stability, transport, and transcriptional regulation. James Manley's laboratory at Columbia University (columbia/cu/biology/faculty/manley/) provides "In Vitro Sumoylation of Recombinant Proteins and Subsequent Purification for Use in Enzymatic Assays," a protocol for modifying proteins in this manner, allowing one to assess the impact of sumoylation. This method is freely accessible on the website for Cold Spring Harbor Protocols (cshprotocols/cgi/content/full/2009/1/pdb.prot5121).







About Cold Spring Harbor Protocols:



Cold Spring Harbor Protocols (cshprotocols) is a monthly peer-reviewed journal of methods used in a wide range of biology laboratories. It is structured to be highly interactive, with each protocol cross-linked to related methods, descriptive information panels, and illustrative material to maximize the total information available to investigators. Each protocol is clearly presented and designed for easy use at the bench - complete with reagents, equipment, and recipe lists. Life science researchers can access the entire collection via institutional site licenses, and can add their suggestions and comments to further refine the techniques.



About Cold Spring Harbor Laboratory Press:



Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit cshlpress.



Source: David Crotty


Cold Spring Harbor Laboratory