Merger Between A Phospholipid Membrane 'bubble' And A Water-Filled Network Of Polymer Chains May Offer New Drug Delivery Method

People have been combining materials to bring forth the best properties of both ever since copper and tin were merged to start the Bronze Age. In the latest successful merger, researchers at the National Institute of Standards and Technology (NIST), the University of Maryland (UM) and the U.S. Food and Drug Administration (FDA) have developed a method to combine two substances that individually have generated interest for their potential biomedical applications: a phospholipid membrane "bubble" called a liposome and particles of hydrogel, a water-filled network of polymer chains. The combination forms a hybrid nanoscale (billionth of a meter) particle that may one day travel directly to specific cells such as tumors, pass easily though the target's cell membrane, and then slowly release a drug payload.



In a recent paper in the journal Langmuir*, the research team reviewed how liposomes and hydrogel nanoparticles have individual advantages and disadvantages for drug delivery. While liposomes have useful surface properties that allow them to target specific cells and pass through membranes, they can rupture if the surrounding environment changes. Hydrogel nanoparticles are more stable and possess controlled release capabilities to tune the dosage of a drug over time, but are prone to degradation and clumping. The researchers' goal was to engineer nanoparticles incorporating both components to utilize the strengths of each material while compensating for their weaknesses.



To manufacture their liposome-hydrogel hybrid vesicles, the researchers adapted a NIST-UM technique known as COMMAND for COntrolled Microfluidic Mixing And Nanoparticle Determination that uses a microscopic fluidic (microfluidic) device (see "NIST, Maryland Researchers COMMAND a Better Class of Liposomes" in NIST Tech Beat, April 27, 2010). In the new work, phospholipid molecules are dissolved in isopropyl alcohol and fed via a tiny (21 micrometers in diameter, or three times the size of a yeast cell) inlet channel into a "mixer" channel, then "focused" into a fluid jet by a water-based solution added through two side channels. Hydrogel precursor molecules are mixed in with the focusing fluid.



As the components blend together at the interfaces of the fluid streams, the phospholipid molecules self-assemble into nanoscale vesicles of controlled size and trap the monomers in solution inside. The newly formed vesicles then are irradiated with ultraviolet light to polymerize the hydrogel precursors they carry into a solid gel made up of cross-linked chains. These chains give strength to the vesicles while permitting them to retain the spherical shape of the liposome envelope (which, in turn, would facilitate passage through a cell membrane).



To turn the liposome-hydrogel hybrid vesicles into cellular delivery vehicles, a drug or other cargo would be added to the focusing fluid during production.



* J.S. Hong, S.M. Stavis, S.H. DePaoli Lacerda, L.E. Locascio, S.R. Raghavan and M. Gaitan. Microfluidic directed self-assembly of liposome-hydrogel hybrid nanoparticles. Langmuir, published online April 29, 2010.



Source:

Michael E. Newman

National Institute of Standards and Technology (NIST)

New Study Raises Questions About Prostate Cancer Therapies Targeting Insulin Like Growth Factor Receptor

Therapies under development to treat
prostate cancer by inhibiting the ability of insulin-like growth factor
(IGF-1) to activate its target receptor could have unexpected results,
especially if a major tumor suppressor gene -- p53 -- is already
compromised, according to new research by investigators at Fred Hutchinson
Cancer Research Center.



IGF-1 is a polypeptide hormone that can influence growth,
differentiation and survival of cells expressing the type 1 receptor
(IGF-1R). Past clinical, epidemiological and experimental studies have
strongly implicated IGF-1 as a contributing factor in the natural history
of prostate cancer. However, very little has been done to prove absolutely
that the expression or activation of the IGF-1 signaling pathway at
physiologically relevant levels is sufficient to cause a healthy prostate
cell to become a cancer cell.



Norman Greenberg, Ph.D., and colleagues conducted a pair of experiments
by manipulating gene expression directly in the epithelial compartment of
the mouse prostate gland to better understand the role of IGF-1R. In
contrast to studies that correlated elevated levels of IGF-1 with the risk
of developing prostate cancer, Greenberg's research showed that eliminating
IGF-1R expression in an otherwise normal mouse prostate caused the cells to
proliferate and become hyperplastic. Although persistent loss of IGF-1R
expression ultimately induced cell stasis and death, both of these
processes are regulated by the tumor suppressor gene p53 that is commonly
mutated in human prostate cancers. Hence the researchers hypothesized that
tumors with compromised p53 might not respond predictably to therapies
targeting IGF1 signaling.



To test their reasoning they conducted a second experiment by crossing
mice carrying the prostate-specific IGF-1R knockout alleles with transgenic
mice that develop spontaneous prostate cancer when p53 and select other
genes are compromised. The results were as predicted: Prostate
epithelial-specific deletion of IGF-1R facilitated the emergence of
aggressive prostate cancer in the genetically-engineered tumor prone mice.



Published in the May 1 edition of Cancer Research, the study supports a
critical role for IGF-1R signaling in prostate tumor development and
identifies an important IGF-1R-dependent growth control mechanism,
according to the authors. Title of the paper is "Conditional deletion of
insulin-like growth factor-1 receptor in prostate epithelium."



"If our predictions hold true, tumor cells with intact p53 may show the
best response to therapy targeting the IGF-1R signal, however when p53 is
not functioning normally, response to this therapy may not be as expected,"
said Greenberg, the study's corresponding author and a member of the
Hutchinson Center's Clinical Research Division.



Greenberg's message to clinicians who administer IGF-R1 therapy: "We're
all hoping for good results but let's proceed with caution."



A search of the database for clinical trials registered with the
National Cancer Institute found 18 trials in process that use therapies to
inhibit IGF-R1. None of them include a tumor's p53 status as a criterion
for recruiting research participants, said Greenberg.



In addition to lead author Brent Sutherland, Ph. D., of the Hutchinson
Center, contributing research also came from scientists at Baylor College
of Medicine in Houston, Texas, the Center for Cancer and Stem Cell Biology
at Texas A&M University and the Institut National de la Sante et de la
Recherche Medicale in Paris, France.



The study was funded by the National Cancer Institute, the Prostate
Cancer Foundation and Phi Beta Psi.


At Fred Hutchinson Cancer Research Center, our interdisciplinary teams
of world-renowned scientists and humanitarians work together to prevent,
diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers,
including three Nobel laureates, bring a relentless pursuit and passion for
health, knowledge and hope to their work and to the world. For more
information, please visit fhcrc.


Fred Hutchinson Cancer Research Center

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Generic Biologic Drugs Unlikely To Offer Significant Savings

Generic versions of a class of medicines called "biologics" would not be significantly cheaper than brand-name versions of the medicines, according to research from professors at Duke University's Fuqua School of Business.



Biologics are drugs, vaccines and other medicines produced by living cells in controlled circumstances. The way they are made differs from traditional pharmaceutical drugs that are produced by industrial-scale chemistry.



Insulin is a common biologic prescribed to treat diabetes; other biologics treat arthritis, cancer and other diseases.



The Food and Drug Administration currently does not have a process for the review and approval of generic versions of biologic products, several of which are scheduled to lose their patent protection this year.



"Congress and the FDA are currently addressing this issue and developing a process for the oversight of generic biologics, partially in hopes of generating significant cost savings for consumers and insurers," said Kevin Schulman, a professor of medicine and business administration and director of Duke's Health Sector Management program.



"However, our research indicates that any savings to be expected from the addition of generic biologics to the marketplace will be significantly less than the savings generally available from generic pharmaceuticals," Schulman said.



The manufacture of biologics by living organisms through a process that resembles fermentation must be closely monitored to ensure that the final products meet quality and safety standards.



"Our calculations indicate that policy-makers should not assume significant price reductions from generic biologics," said Henry Grabowski, a professor of economics and director of Duke's Program in Pharmaceuticals and Health Economics. "If the discount is small, and patients are achieving good outcomes with the branded product, then generics might get only a small market share," Grabowski said.



The research team, which also included David Ridley, a professor in Duke's Fuqua School of Business, will publish the paper, "Entry and Competition in Generic Biologicals," in the journal Managerial and Decision Economics. The research was funded by Genentech, which produces biologics.



In order to predict prices of generic biologics, the researchers combined a theoretical model of generic biologics with historical data from the generic pharmaceutical market.



Generic pharmaceutical products are widely accepted as a less-expensive alternative to brand-name drugs. Companies are able to sell generics for less because they do not have to repeat the studies required to win initial approval from the FDA. If manufactured according to the standards set forth for the initial approval of the treatment, the generic product is assumed to have the same safety and efficacy profile as the branded version.



Because of their unique characteristics, however, generic biologics probably face higher clinical, manufacturing and marketing costs to enter the market, according to the researchers.



Another barrier for generic biologics is that they probably will not be approved by the FDA as therapeutically equivalent to the reference brand, the researchers said. Generic pharmaceuticals can be substituted for the brand name by a pharmacist under state substitution laws aimed at cutting prescription costs. But without equivalency, a physician would specifically have to prescribe the generic biologic.



In recent congressional testimony, Grabowski called for a 10-year period in which makers of generic biologics could not use data developed by makers of original products in marketing applications for generic biologics. Otherwise, generics potentially could enter the market before originators have earned a positive return on their sizeable investments in research and development, he said.



U.S. Rep. Henry Waxman, D-Calif., and U.S. Sens. Hillary Rodham Clinton, D-N.Y., and Charles Schumer, D-N.Y., have introduced legislation that would subsidize companies that produce generic biologics. But Duke's David Ridley says that even with such legislation, "prices might not fall enough to justify the cost to taxpayers of such a program."



"We understand the enthusiasm for lower prices for these biologics," he said. "But 'generic' is not necessarily synonymous with 'cheap.' Whether generic biologics have low prices will depend on how many generic biologic manufacturers enter the market."







Contact: Laura Brinn


Duke University

Maternal Separation And Gene Expression In Monkeys

Michael J. Sabatini, Philip Ebert, David A. Lewis, Pat Levitt, Judy L. Cameron, and K'roly Mirnics


Even most dads will admit there's nothing quite like mom when you are young. In this week's Journal, Sabatini et al. investigated the neural substrate of behaviors caused by maternal separation of monkeys at either 1 week or 1 month of age. Using DNA microarrays, the authors identified a single gene that was differentially regulated in 1 week and 1 month separation animals: the nitric oxide signaling molecule GUCY1A3, an analog of rat guanylate cyclase 1 - 1. In maternally reared control monkeys, in situ hybridization showed that GUCY1A3 was expressed at highest levels in the amygdala, and was expressed maximally by 1 week of age. Expression was significantly lower in 1 week maternally separated animals and was intermediate in 1 month separated monkeys. GUCY1A3 expression correlated with acute and long-term self- and social-comforting behaviors. Whether GUCY1A3 is simply a marker of this behavior or plays a causal role remains to be determined.







News tips from the Journal of Neuroscience



Contact: Sara Harris


Society for Neuroscience

Cilia Get The Message Across In Early Embryos

Having your heart in the right place usually means having it located on the left side of your body. But just how a perfectly symmetrical embryo settles on what's right and what's left has fascinated developmental biologists for a long time. The turning point came when the rotational beating of cilia, hair-like structures found on most cells, was identified as essential to the process.



Now, scientists at the Salk Institute for Biological Studies take a step back and illuminate the molecular process that regulates formation of cilia in early fish embryos. In a study published in a forthcoming issue of Nature Genetics, the Salk team, led by Juan Carlos Izpisua Belmonte, Ph.D., a professor in the Gene Expression Laboratory, identified a novel factor that links early developmental signals with the function of cilia and their role in controlling left-right specification in zebrafish.



"When we altered the function of the gene duboraya, we saw problems with cilia formation, although the gene product itself is not a part of the structure. This opens up a new area of research," says Belmonte.



Cilia have been known to cell biologists for over a hundred years. Belmonte is convinced that these humble structures, which have until recently been ignored by physiologists and molecular biologists alike, are poised to take center stage in the field of biology. Explains Belmonte: "When you impair the function of cilia or the flow of cilia, you create substantial problems throughout the body."



These simple, whip-like structures are not only critically involved in specifying left-right sidedness during development, but they help move fluid and mucus around the brain, lung, eye and kidney, and are required for smell, sight and reproduction. Medical conditions, such as diabetes and obesity, have been linked to structural defects in the architecture or in function of cilia. Moreover, recent evidence indicates that cilia may have additional roles in controlling skeletal development and brain function.



Cilia on the outer surface of the embryo's underside, an area called the ventral node in mammals, exhibit a characteristic twirling movement that wafts chemical messengers over to the left side. This sets up a chemical concentration gradient that tells stem cells how and where to develop. When cilia function is impaired, organs like the heart, lungs, and liver may end up on the wrong side of the body.



When postdoctoral researcher and first author Isao Oishi, Ph.D., searched for genes in zebrafish involved in the left-right patterning of early embryos, he expected to find genes encoding components of cilia. "Instead we found a non-structural cilia gene that influences the function of the cilia, and that, among other things, caused problems with left/right patterning," he says. He named the gene duboraya after the shape of the Japanese duboraya lantern, which fish with an inactivated version of the gene assume as they develop.



Oishi discovered that duboraya is required for formation of fully functional cilia in Kupffer's vesicle, the fish equivalent of the mammalian ventral node. Without duboraya, cilia were reduced to short stumps, unable to create the counterclockwise flow needed to establish left versus right. Duboraya protein, he found, is activated by frizzled-2, a member of the highly conserved Wnt signaling pathway, which orchestrates the activities of a vast number of cells during embryonic development.



Explains Belmonte: "We could show that genes that sense their external or internal environment communicate with structural genes that are responsible for making the cilia and tell them to beat this way or that way. What Isao discovered is a mechanism of how they relay information."







Researchers who contributed to the work include postdoctoral researchers Yasuhiko Kawakami, Ph.D., and Carles Callol-Massot, Ph.D., both at Salk, and Angel Raya, M.D., Ph.D., formerly at Salk and now scientific co-ordinator at the Center of Regenerative Medicine in Barcelona, Spain.



The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.



Contact: Gina Kirchweger


Salk Institute

Novel Strategies For Healthy Ageing

Protein degradation and malfunction is a major cause of ageing and can be the result of attacks on proteins by other molecules. One of these processes, called glycation, involves the spontaneous attack by sugars on proteins. If glycation gets out of hand many proteins are degraded or destroyed proteins which are important for the proper functioning of the body. Protection against glycation declines with age leading to increasing glycation damage with increasing age. A critical enzyme involved in protection against glycation is "Glyoxalase 1". Using a model nematode system, Professor Paul Thornalley (University of Warwick) and his collaborators at the University of Heidelberg have shown for the first time that by enhancing levels of glyoxalase I the glycation process can be diminished and life can be extended by up to 40%. Similarly, by decreasing amounts of the enzyme they have shortened the lifespan of the nematodes. Professor Thornalley will present the results at the Society for Experimental Biology's Annual Main Meeting on Sunday 1st April.


"This work shows for the first time that this enzyme also protects proteins against damage by oxidation and nitration", says Professor Thornalley. The enzyme works by converting the damaging reactive products of glycation derived from glucose into harmless compounds. "This implies that glycation promotes multiple types of protein damage in ageing", says Prof Thornalley who will present his findings in the same session as plant scientist, Professor Dr Sudhir Sopory (International Center for Genetic Engineering and Biotechnology, New Delhi).


Professor Sopory has shown in tobacco and rice plants that increasing glyoxalase 1 enhances resistance to stress conditions, which demonstrates that the enzyme plays a similar role in both animal and plant systems in preventing protein damage.


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Finnish Scientists Discovered A New Approach To Treat Virus-induced Lymphomas

Kaposi's sarcoma herpesvirus (KSHV) is a human tumor virus and an etiological agent for Kaposi's sarcoma and primary effusion lymphoma (PEL). PELs are aggressive lymphomas with reported median survival time shorter than six months after diagnosis. Researchers at the University of Helsinki have discovered that activation of the p53 pathway offers a novel effective treatment modality for KSHV-infected lymphomas.


The findings by the research group of Dr. Päivi Ojala (University of Helsinki) in collaboration with the groups of Professor Marikki Laiho (University of Helsinki), Dr. Pirjo Laakkonen (University of Helsinki), and Dr. Jürgen Haas (Max von Pettenkofer Institute, Munich & University of Edinburgh) open new options for exploiting reactivation of p53 as a novel and highly selective treatment modality for this virally-induced lymphoma. The project involves scientists from two Academy of Finland National Centre of Excellence Programs, the Translational Genome-Scale Biology and Cancer Biology.


TP53 gene encodes a transcription factor (p53) that plays a central role in protecting cells from tumor development by inducing cell-cycle arrest or apoptosis via a complex signal transduction network referred to as the p53 pathway. TP53 gene is mutated or deleted in 50% of all malignant tumors. A recently discovered strategy for p53 activation targets the interaction of p53 with its negative regulator MDM2. This is based on a potent and selective small-molecule inhibitor of the p53-MDM2 interaction, the Nutlin-3a, originally discovered by Dr Lyubomir T Vassilev (Roche Research Center, Nutley, NJ., USA). Nutlin-3a has been suggested to be a potential treatment option for cancers with wt p53.


PEL is a non-Hodgkin type lymphoma latently infected with KSHV, and it manifests as an effusion malignancy in Kaposi's sarcoma patients. There are no current therapies effective against the aggressive KSHV-induced PEL. KSHV displays two patterns of infection: latent and lytic phase. During latency, only a restricted set of viral genes is expressed. The KSHV genome encodes several homologues of cellular proteins, which engage cellular signaling pathways, govern cell proliferation and modulate apoptosis.


Majority of the PELs appear to have an intact TP53 gene suggesting that genetic alterations are not selected for during PEL tumorigenesis. The results of this study demonstrate binding of the KSHV latency associated antigen LANA to both p53 and MDM2, and that the MDM2 inhibitor Nutlin-3a disrupts the p53-MDM2-LANA complex and selectively induces massive apoptosis in PEL cells. The cytotoxic effect of Nutlin-3a was specific for the KSHV-infected cells since Nutlin-3a did not induce apoptosis in lymphoblastoid cell lines transformed with another human tumor virus, the Epstein-Barr virus, despite of their wt p53 status.


Moreover, the researchers show that Nutlin-3a has striking anti-tumor activity in vivo in a mouse xenograft model for the PEL. Nutlin-3a treatment resulted in a marked regression of all tumors in the treated animals in two weeks. These results demonstrate that p53 reactivation via Nutlin-3a is an efficient treatment for KSHV-lymphomas in mice and suggest a novel therapeutic strategy for treatment of these fatal virus-induced malignancies also in humans.


This work was supported by grants from the Academy of Finland including also Centres of Excellence in Translational Genome-Scale Biology and Cancer Biology, and additional funds have been obtained from the University of Helsinki, Academy of Finland research program for Systems Biology and Bioinformatics, Finnish Cancer Foundations, Sigrid Juselius Foundation, and from the European Union (FP6 INCA project LSHC-CT-2005-018704).


About HELSINGIN YLIOPISTO (UNIVERSITY OF HELSINKI)


Founded in Turku in 1640, the University moved to Helsinki in 1828. The University of Helsinki has nine faculties: Theology, Law, Medicine, Arts, Science, Education, Social Sciences, Agriculture and Forestry, Veterinary Medicine.



HELSINGIN YLIOPISTO (UNIVERSITY OF HELSINKI)

P.O. Box 33

FIN-00014 Helsinki

helsinki.fi/

Laser Wave Steers Electrons In Chemical Bonds

As is now reported in Science (April, 2006), a team of scientists from the Netherlands (FOM Institute for Atomic and Molecular Physics (AMOLF), Amsterdam) and Germany (Max-Planck-Institute of Quantum Optics (MPQ), Garching and the Universities of Bielefeld and Hamburg) has demonstrated that the detailed shape of the electric field inside a short light pulse can be used to control the motion of electrons involved in chemical bonding and to change the outcome of a simple chemical reaction. This result - obtained on the dissociation of D2 molecules - may open a new way of steering intra-molecular electron transfer processes like those in DNA base-pairs.



Intense light pulses of the order of a few femtoseconds (1 femtosecond is one millionth-of-a-billionth of a second) are capable of exerting a force on electrons that is comparable in strength to the inner-atomic forces that hold electrons on their orbits around the nucleus. In order to exert these forces on electrons in a controlled way, pulses of laser light with a precisely reproducible waveform are needed.



In 2002 Prof. Ferenc Krausz, director at the MPQ (at that time Professor at the Vienna University of Technology), succeeded in cooperation with Prof. Theodor Hänsch - using the Nobel price awarded frequency comb technique - in developing "phase-controlled" laser pulses: Here not only intensity and frequency but also the phase of the carrier-envelope is precisely defined and reproducible.



Special about a laser pulse with reproducible phase is that minima and maxima of the electric field occur each time at the same position within the pulse. By varying the phase, the timing of minima and maxima can be varied with respect to the pulse peak, changing the form of the wave significantly, if the pulse comprises only few wave cycles. The team of Prof. Krausz and their collaborators have since demonstrated the utility of phase-controlled laser pulses to generate attosecond light pulses (1 attosecond is a billionth-of-a-billionth of a second) and to control the motion of electrons in and around atoms on an attosecond time scale. The question posed in the current work by the Dutch-German research team was if electrons that are involved in chemical bonding in a molecule can be steered by the electric field of phase-controlled laser pulses in a similar way, and - if yes - can this light-driven electronic motion affect reaction dynamics.



At MPQ, Dr. Matthias Kling (post doc in the group of Prof. Marc Vrakking) and his collaborators studied the influence of intense linearly-polarized laser pulses with duration of 5 femtoseconds on the motion of electrons in a chemical bond. In the experiments, positively-charged deuterium molecules (D2+), also known as heavy hydrogen, were used. These molecules are very simple: they consist of two positively charged ions (the D+ nuclei, each containing a proton and a neutron), and one electron that is left behind following ionization of neutral D2 with a laser pulse. With a special camera that was developed at AMOLF, the Dutch-German team of scientists measured the emission direction of deuterium ions (D+) and deuterium atoms (D) after dissociation of D2+ molecules with respect to the laser polarization axis.
















As long as the scientists used conventional laser pulses without phase control, equal numbers of deuterium ions (as well as atoms) were ejected in both directions along the laser polarization axis. Using phase-controlled pulses with a specific value of the phase (j = 0, see upper panel of the figure), deuterium ions and deuterium atoms were preferentially emitted to the right and left, respectively. A simple shift of the phase to j = 180 degree, resulting in the same waveform with the oscillations flipped around the propagation axis (see upper panel of the figure), turns the outcome of this simple laser-induced reaction into the opposite: the D+ ions preferable fly to the left and the D atoms to the right.



On the basis of quantum mechanical calculations the scientists can explain the observed phenomenon. Before exposure to the light wave, the electron is in its lowest-energy state. It is found predominantly between the two deuterium ions (see figure). The strong laser field, directed along the axis of the molecule, enforces the electron to get localized on the right or left side of the chemical bond in an oscillatory fashion. The timing of this electron "hopping" can be controlled with the phase of the laser wave. In quantum mechanical terms, this localization is possible because the laser excites the electron to a so-called coherent superposition state. This softens the bonding between the two positively-charged nuclei, which consequently start moving apart, with the electron hopping between them whilst the molecule disintegrates. When the molecule breaks up into two fragments the electron settles on one them (which remains neutral), while the other fragment is detected in the experiment as a positively charged ion. Since the dissociation of the molecule requires a characteristic time, the scientists can - by choosing the phase - selectively drive the electron to be on the desired ion at the time of fragmentation.



Processes, in which electrons are transported, are extremely important in chemistry and biology. For example, electron transfer plays an important role in both damage and repair of DNA. The here described results of the Dutch-German research team on the dissociation of hydrogen molecules may provide a clue how to control the transfer of electrons in larger systems using the electric field of light. This work may also have an impact on the new field of molecular electronics, where the flow of electrons between molecules may be steered in a controlled way with laser pulses.







Contact: Prof. Dr. Ferenc Krausz

ferenc.krauszmpq.mpg

Max-Planck-Gesellschaft

Antisense Therapeutics Scientist Out To Pull More Big Deals

Aiming for more major licensing deals like the one his company recently secured with top 20 global pharmaceutical company, Teva, is front of mind for rising Australian biotechnology star, Antisense Therapeutics Ltd (ASX code: ANP)Research Director Dr Christopher Wraight when he meets with leading industry figures in the US in May.



One of two Australian life scientists chosen from a highly competitive field of candidates for the prestigious 2008 Advancing BioBusiness Award, Dr Wraight will attend the world's largest biotechnology meeting, the Biotechnology Industry Organisation (BIO) convention, which attracts over 22,000 delegates from around the globe.



A tailored program of meetings will also be scheduled for him with leading American players including venture capital firms, research institutes, biotechnology entrepreneurs and biopharmaceutical companies, to help build valuable international networks, knowledge and collaborations.



The Advancing BioBusiness Award is an innovative scheme by Merck Sharp & Dohme and Advance, a dynamic, diverse global community of Australian professionals overseas committed to advancing Australia and Australians.



Through the Advancing BioBusiness Award, Dr Wraight said he wants to expand important global connections for Australian science and help facilitate more international business by better understanding what US pharmaceutical companies are looking for in new drug therapies at each stage of what is typically a 10-15 year development process.



"Our ultimate customer is the patient. For most Australian pharmaceutical biotechs, however, big pharmaceutical companies are the first customers we need to think about. To provide better drugs for patients we first need to build better research and development programs to attract the best commercialisation partners," Dr Wraight said.



"Before they license drugs from biotechs, pharmaceutical companies scrutinise our drug R&D programs with very demanding and sophisticated due diligence processes around very long-term planning horizons. Biotechs sometimes fall at the last hurdle, failing to execute a deal because decisions taken early in their drug development program did not anticipate the future needs of their prospective partner," he said.



Dr Wraight said that establishing relationships with a range of key US decision-makers will facilitate soundconsultation throughout each stage of development to optimise eventual success at the negotiating table.



Senator Kim Carr, Minister for Innovation, Industry, Science and Research, said:



"The Advancing BioBusiness Award complements the Rudd Government's policy of promoting innovation and commercialisation in the biotechnology and pharmaceutical sector, encouraging closer links between Australian biotech and global pharmaceutical companies, and helping Australian biotechs access global supply chains."



Dr Phil Kearney, Merck Sharp & Dohme's manager for external scientific affairs, said Australia is recognised for its excellence in medical research and its vigorous and creative biopharmaceutical industry. However the number of drug development projects which reach advanced clinical development is only a quarter of what would be predicted on the basis of our output in scientific literature.



"By immersing two of our top biotechnology people in successful commercial research centres in the United States, and providing them with opportunities to share their learning back at home, we aim to build a stronger Australiancapability to win in this highly competitive global knowledge market," he said.



The other recipient of the 2008 Advancing BioBusiness Award is Dr Raisa Monteiro, Research Director of DendriMed.







Source: Jackie Crossman


Research Australia

Major Pathologies Associated With Alzheimer's Disease Reduced In Mice With Novel Gene

A new study reveals that a previously undiscovered mouse gene reduces the two major pathological perturbations commonly associated with Alzheimer's disease (AD). The research, published by Cell Press in the November 12 issue of the journal Neuron, finds that the novel gene interacts with a key cellular enzyme previously linked with AD pathology, thereby uncovering a new strategy for treating this devastating disorder.



AD is an incurable neurodegenerative disease characterized by a pathological accumulation of extracellular sticky amyloid beta (A-) protein plaques and intracellular hyperphosphorylated tau protein aggregations, called neurofibrillary tangles (NFT), in the brain. Previous research has suggested that glycogen synthase kinase-3 (GSK-3), an enzyme that is essential for many critical cellular functions, may play a role in both A- plaque and NFT generation.



"Because GSK-3 regulates two major pathological hallmarks of AD, manipulation of its activity is an attractive potential therapeutic strategy for AD," explains senior study author Dr. Huaxi Xu, professor and acting director of the Neurodegenerative Disease Research Program at the Burnham Institute for Medical Research in La Jolla, California. "Identification of new genes involved in these processes will be instrumental in developing novel AD therapeutics."



Using a sophisticated genetic screening approach that finds genes based on their functions, Dr. Xu and colleagues identified the novel mouse gene Rps23r1. RPS23R1 protein reduced levels of A? and hyperphosphorylated tau by interacting with the well known adenylate cyclase/cAMP/PKA signaling pathway and inhibiting GSK-3 activity. Remarkably, the AD-like pathologies of transgenic AD mice were improved after crossing them with Rps23r1 transgenic mice.



Additionally, the researchers demonstrated that RPS23R1 also exerts its function in human cells, suggesting that RPS23R1 signaling pathways are active in humans. "While it is not yet known whether there are functional analogs of RPS23R1 in humans, further elucidation of RPS23R1 functions and mechanism of action may prove to be important for developing new strategies for combating AD and other diseases, including cancer and diabetes, in which the PKA and GSK-3 signaling pathways are centrally involved," concludes Dr. Xu.



The authors also reported that the mouse Rps23r1 gene, whose human counterpart has not yet been identified, was created during evolution through a process called retroposition, in which a gene is "duplicated" through the reverse transcription of mRNA and the "duplicate" is placed in a different location in the cell's DNA. Although most retroposition events result in non-functional duplicates (called pseudogenes), in rare cases, retroposed genes, like Rps23r1, can become functional.



"From the point of view of treating Alzheimer's disease, if we can express the mouse gene in human brain cells, we may be able to control the buildup of amyloid beta and tau neurofibrillary tangles," said Dr. Xu. "From an evolutionary point of view, we have found an example of a retroposed gene that took on a completely new function."



The researchers include Yun-wu Zhang, Xiamen University, Xiamen, China, Burnham Institute for Medical Research, La Jolla, CA; Shijie Liu, Burnham Institute for Medical Research, La Jolla, CA; Xue Zhang, Burnham Institute for Medical Research, La Jolla, CA;Wu-Bo Li, Functional Genetics, Inc., Gaithersburg, MD; Yaomin Chen, Burnham Institute for Medical Research, La Jolla, CA; Xiumei Huang, Xiamen University, Xiamen, China, Burnham Institute for Medical Research, La Jolla, CA; Liangwu Sun, Burnham Institute for Medical Research, La Jolla, CA; Wenjie Luo, The Rockefeller University, New York, NY; William J. Netzer, The Rockefeller University, New York, NY; Richard Threadgill, Functional Genetics, Inc., Gaithersburg, MD; Gordon Wiegand, Functional Genetics, Inc., Gaithersburg, MD; Ruishan Wang, Xiamen University, Xiamen, China, Burnham Institute for Medical Research, La Jolla, CA; Stanley N. Cohen, Stanford University School of Medicine, Stanford, CA; Paul Greengard, The Rockefeller University, New York, NY; Francesca-Fang Liao, Burnham Institute for Medical Research, La Jolla, CA, University of Tennessee Health Science Center College of Medicine, Memphis, TN; Limin Li, Functional Genetics, Inc., Gaithersburg, MD, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; and Huaxi Xu, Burnham Institute for Medical Research, La Jolla, CA.



Source: Cathleen Genova


Cell Press

Lasers To Align Molecules At Argonne

Protein crystallographers have only scratched the surface of the human proteins important for drug interactions because of difficulties crystallizing the molecules for synchrotron x-ray diffraction.



Scientists at the U.S. Department of Energy's (DOE) Argonne National Laboratory have devised a way to eliminate the need for crystallization by using lasers to align large groups of molecules.



"Strong laser fields can be used to control the behavior of atoms and molecules," Argonne Distinguished Fellow Linda Young said. "Using x-rays, we can investigate their properties in a totally new way."



Crystallization allows scientists to create a periodic structure that will strongly diffract in specific directions when bombarded with x-rays. From the resulting diffraction pattern, a real-space image can be reconstructed.



However, without crystallization, when x-rays collide with multiple, randomly oriented molecules, they diffract in different directions, making it impossible to create a composite diffraction image, Argonne Physicist Robin Santra said.



Some molecules, such as many involved with drug interaction, cannot be crystallized and imaging would require numerous samples to bombard in order to get a full composite picture. Young's laser technique allows for millions of molecules suspended in a gaseous state to be aligned so that when bombarded with x-rays, they all diffract in the same way. The resulting images are at atomic level resolution and do not require crystallization.



"Understanding the structure of the approximately 1 million human proteins that cannot be crystallized is perhaps the most important challenge facing structural biology," Young said.



"A method for structure determination at atomic resolution without the need to crystallize would be revolutionary."



Young and her team have successfully aligned molecules using a laser, probed the aligned ensemble with x-rays and shown theoretically that the technique could be used for x-ray imaging (See E. R. Peterson et al., Applied Physics Letters 92, 094106 (2008)), but they require an proposed upgrade to the Advanced Photon Source facility located at Argonne before x-ray diffraction can be done experimentally.







Funding for this research was provided by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences.



The mission of the Basic Energy Sciences (BES) program - a multipurpose, scientific research effort - is to foster and support fundamental research to expand the scientific foundations for new and improved energy technologies and for understanding and mitigating the environmental impacts of energy use. The portfolio supports work in the natural sciences, emphasizing fundamental research in materials sciences, chemistry, geosciences, and aspects of biosciences.



Argonne National Laboratory brings the world's brightest scientists and engineers together to find exciting and creative new solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.



Source: Brock Cooper


DOE/Argonne National Laboratory

German-Russian Collaboration In International Research

An important part of the mission of the FAIR Russia Research Centre (FRRC), to be jointly financed by ROSATOM and the Helmholtz Association, will be to provide opportunities for young, high-calibre Russian scientists to be involved in the construction of FAIR. Doctoral and postdoctoral candidates from Russia will enjoy highly favourable working conditions at the FRRC in addition to involvement in international research. Promising young foreign scientists visiting the FRRC will benefit from the knowledge of outstanding Russian physicists while gaining exposure to Russia's dynamic research infrastructure. "This represents another milestone in German-Russian collaboration, which is something we value highly and have been expanding for many years," said Professor JГјrgen Mlynek, President of the Helmholtz Association.



The involvement of the Helmholtz Association with Russian scientific research goes even further however. Together with the Russian Foundation for Basic Research, the first eight Helmholtz Russia Joint Research Groups were selected from a field of 25 applications. Each of these research groups, composed primarily of up-and-coming German and Russian research scientists, will be provided an annual budget of €150,000 for a period of three years. The funds will be used for joint experiments and expeditions as well as to create more attractive working conditions for next-generation Russian scientists in their home country in parallel to their inclusion in major international research projects conducted by the Helmholtz Association.



The following Helmholtz Russia Joint Research Groups were selected:



Title: Physics Analysis and Calorimetry at the Terascale

German Partner: Deutsches Elektronen-Synchtrotron

Russian Partner: Institute for Theoretical and Experimental Physics (ITEP)

German Co-leader: Dr. Kerstin Borras

Russian Co-leader: Dr. Roman Mizuk



Title: High Dose Irradiation Damage of RAFM Steels

German Partner: Forschungszentrum Karlsruhe

Russian Partner: Ulyanovsk State University

German Co-leader: Dr. Ermile Gaganidze

Russian Co-leader: Dr. Viacheslav V. Svetukhin



Title: Hydrogen Isotopes Retention in First-Wall Materials for ITER and Fusion Power Reactors

German Partner: Max-Planck-Institut fГјr Plasmaphysik

Russian Partner: Moscow Engineering and Physics Institute (MEPhI)

German Co-leader: Dr. Matej Mayer

Russian Co-leader: Dr. Anna V. Golubeva



Title: Molecular pathogenesis of bilateral breast cancer

German Partner: German Cancer Research Centre

Russian Partner: N.N. Petrov Institute of Oncology

German Co-leader: Prof. Dr. Manfred Schwab

Russian Co-leader: Evgeny N. Suspitsin, MD., PhD



Title: Structural aspects of biocompatible ferrofluids by scattering methods: Stabilization, properties control and applications

German Partner: GKSS-Forschungszentrum Geesthacht

Russian Partner: Joint Institute for Nuclear Research (JINR)

German Co-leader: PD Dr. Regine Willumeit

Russian Co-leader: PD Dr. Mikhail Avdeev



Title: ECOLINK - Understanding effects of environmental toxicants at population and community levels: A link between ecotoxicological experiments and field observations within Eurasian climate scenarios UFZ

German Partner: Helmholtz Centre for Environmental Research - UFZ

Russian Partner: Institute of Systematics and Ecology of Animals, SB RAS

German Co-leader: PD Dr. Matthias Liess

Russian Co-leader: Dr. (C.Sc.)Yury Yurchenko



Title: Actinide nano-particles: formation, stability, and properties relevant to the safety of nuclear waste disposal

German Partner: Forschungszentrum Karlsruhe

Russian Partner: Chemistry Department of Lomonosov Moscow State University (MSU)

German Co-leader: Dr. Melissa A. Denecke

Russian Co-leader: Dr. Stepan N. Kalmykov
















Title: Derivation of germ line competent rat ES cells for gene targeting

German Partner: Max DelbrГјck Centre for Molecular Medicine Berlin-Buch

Russian Partner: Institute of Cytology, Russian Academy of Sciences

German Co-leader: Dr. Natalia Alenina

Russian Co-leader: Alexey Tomilin, PhD







The Helmholtz Association has been commissioned with performing research which contributes substantially to answering the grand challenges of science, society and industry through scientifically excellent efforts in six research fields: Energy, Earth and Environment, Health, Key Technologies, Structure of Matter plus Transport and Space. The Helmholtz Association is Germany's largest scientific research association. A total of 25,700 staff work in its 15 research centres. The association's annual budget runs to more than € 2 billion. Its research stands in the tradition of the universal scholar Hermann von Helmholtz (1821-1894). helmholtz/



Source: Thomas Gazlig


Helmholtz Association of German Research Centres

Potential Anti-Obesity And Anti-Cancer Drugs: Groundbreaking Study On Complex Movements Of Enzymes

A groundbreaking study has revealed in great detail how enzymes in the cell cooperate to make fat. These enzymes are integrated into a single molecular complex known as fatty acid synthase. This complex is regarded as a potential target for developing new anti-obesity and anti-cancer drugs.



Dr. Stuart Smith, at Children's Hospital Oakland Research Institute, collaborated with Drs. Edward Brignole and Francisco Asturias from The Scripps Research Institute in La Jolla, Calif. in a study published in the February 2009 edition of Nature Structural and Molecular Biology and featured on the cover of the journal.



"Fatty Acid Synthase is a remarkably complex structure. It contains all of the components needed to convert carbohydrates into fat," Dr. Smith explained. "We have suspected for some time that the enzyme complex is extremely flexible, which makes it difficult to analyze using X-ray crystallography. Last year the X-ray structure of the complex was solved by a group in Switzerland, but this structure provided only a snapshot of the complex in one of its many poses. We were able to use state-of-the-art electron microscopy to obtain images of the complex in many of its different conformations and assemble these images into a movie that displays the full range of motion of the components of the complex." The results reveal how enzymes that appear distantly located in the X-ray structure are able to make the contacts with each other needed for catalysis. The extraordinary swinging, swiveling and rolling motions of fatty acid synthase are represented on the cover of the journal in the form of a flamenco dancer.



Some pharmaceutical companies are focusing on inhibitors of fatty acid synthase because they are known to block the conversion of carbohydrates into fat and suppress appetite as well as slow the growth of cancer cells. Structural information garnered from X-ray and electron microscope images may aid in the design of more effective inhibitors that could be used therapeutically.







About Children's Hospital & Research Center Oakland



Children's Hospital & Research Center Oakland is Northern California's only freestanding and independent children's hospital. Children's is the leader in many pediatric specialties including neonatology, cardiology, neurosurgery and intensive care. The hospital is a designated Level 1 pediatric trauma center and has the largest pediatric critical care facility in the region. Children's Hospital has 190 licensed beds, 201 hospital-based physicians in 30 specialties, more than 2,611 employees and an operating budget of $312 million. Children's research arm, Children's Hospital Oakland Research Institute, has about 300 staff members and an annual budget of more than $49 million. Primary research funding comes from the National Institutes of Health. The institute is a leader in translational blood diseases, developing new vaccines for infectious diseases and discovering new treatment protocols for previously fatal or debilitating conditions such as cancers, sickle cell disease and thalassemia, diabetes, asthma, HIV/AIDS, pediatric obesity, nutritional deficiencies, birth defects, hemophilia and cystic fibrosis.



Source: Diana Yee


Children's Hospital & Research Center at Oakland

Princeton Scientists Find Way To Catalog All That Goes Wrong In A Cancer Cell

A team of Princeton University scientists has produced a systematic listing of the ways a particular cancerous cell has "gone wrong," giving researchers a powerful tool that eventually could make possible new, more targeted therapies for patients.



"For a very long time, cancer therapies have been developed by trial and error to essentially kill a broad variety of rapidly dividing cells, good and bad -- that's why they have massive side effects," said Saeed Tavazoie, a professor in the Department of Molecular Biology and the Lewis-Sigler Institute for Integrative Genomics, who led the research. "The goal of cancer biology is to come up with therapies that are much more rational in terms of attacking the pathways that have been co-opted by cancer cells. The big challenge is to discover these pathways so that we can restore them to their normal state."



Writing in Molecular Cell, Tavazoie, along with his colleagues Hani Goodarzi, a graduate student in molecular biology, and Olivier Elemento, a former postdoctoral researcher in the department, found they were able to systematically categorize and pinpoint the alterations in cancer pathways and to reveal the underlying regulatory code in DNA. Elemento is now on the faculty of Weill Cornell Medical College in New York.



"We are discovering that there are many components inside the cell that can get mutated and give rise to cancer," Tavazoie said. "Future cancer therapies have to take into account these specific pathways that have been mutated in individual cancers and treat patients specifically for that."



The researchers developed an algorithm, a problem-solving computer program that sorts through the behavior of each of 20,000 genes operating in a tumor cell. When genes are turned "on," they activate or "express" proteins that serve as signals, creating different pathways of action. Cancer cells often act in aberrant ways, and the algorithm can detect these subtle changes and track all of them.



"At the present moment, we lump a lot of cancers together and use the same therapy," Tavazoie said. "In the future, we are aiming to be much more precise about treating the exact processes that were perturbed by the mutations."



Pathologists presently examining the tumors of sick patients analyze a small set of tumor characteristics in order to determine the diagnostic and prognostic class to which the cells belong. This new method could give practitioners an encyclopedic accounting of the alterations in problem cells, spelling out the nature of the disease in much greater detail.



The algorithm devised by the group scans the DNA sequence of a given cell -- its genome -- and deciphers which sequences are controlling what pathways and whether any are acting differently from the norm. By deciphering the patterns, the scientists can conjure up the genetic regulatory code that is underlying a particular cancer.



The scientists developed the technique by employing modern methods of systems biology, where researchers seek to understand how components of living systems like cells work together to orchestrate processes, using powerful computers to sort vast arrays of data.



"Part of the promise of genomics and systems biology is the discovery of specific pathways of disease and finding ways to target them precisely," Tavazoie said. "We have focused on revealing what these pathways are."



The challenge for others, he said, will be to design specific therapies for such diseases, a process that could take many years. "This is an important first step," Tavazoie added.



The method ultimately could work for any type of cancer and paves the way for rational approaches to treating a host of other diseases from diabetes to neurological disorders, the scientists said.



The research was funded by the National Human Genome Research Institute of the National Institutes of Health.



Source: Kitta MacPherson


Princeton University

Monoclonal Antibody Therapeutics to Fill Vacuum Left by Ineffective Conventional Therapies

London, UK - 25th January, 2005 - Currently, the limited efficacy of conventional therapies, especially in the case of
several oncology and autoimmune and inflammatory disorders (AIID), is creating the need for safe and effective treatment
alternatives. While this situation has promoted demand for monoclonal antibodies (mAbs), market success will depend on
clearly establishing their clinical and cost benefits.


Unlike several conventional (small molecule) therapies that offer only short-term symptomatic relief and can potentially
cause serious side effects, biopharmaceuticals, such as mAbs, provide effective treatments with greater efficacy and
tolerability.


Amongst the most important attributes of mAbs is their high specificity. The ability to target specific antigens (within
cells, tissues and organs) involved in the pathology of disease, while minimising side effects has underlined the popularity
of mAbs in clinical applications.


Earlier, the attribute of high specificity had restricted the target population that could be treated with mAbs. Now,
numerous mAbs therapeutic products in clinical development are being investigated for the treatment of more than one disease
or for different forms of the same disease.


For instance, Remicade, which initially gained marketing authorisation for the treatment of severe and active Crohn's
disease, was later approved for reducing the signs and symptoms associated with rheumatoid arthritis. Thus, while most
products are expected to be approved initially for specific forms of a disease, label expansion is likely to follow, thereby
expanding the patient population that can be treated and boosting revenue potential.


The improved side effect profile of mAbs offers the patient a well-tolerated therapy, while also lowering overall
disease-management costs. mAbs have also provided significant benefits in terms of extending the survival rate of terminally
ill patients. In contrast, small molecule drugs have been liable to producing undesired side effects that extract heavy costs
in terms of both patient health and financial outlays.


However, even as pharmaceutical and biotechnology companies move towards 'biotech drugs' model from the 'small molecule
blockbuster' model, lower priced small molecule drugs remain the first line treatment choice in comparison to highly priced
mAbs alternatives.


Due to the sizeable development costs involved, most companies have adopted premium pricing for mAb products. High costs
assume increased relevance when mAbs are used in combination with conventional drugs, or in cases where continuous treatment
is required resulting in only very specific patient populations receiving mAbs, and uptake being slow.















"While costs are expected to go down as competition increases and development procedures are refined, the benefits of the
drugs need to be clearly demonstrated in terms of overall cost savings and effectiveness," remarks Frost & Sullivan (healthcare.frost) Industry Manager Dr. Raju Adhikari.



"Biopharmaceutical and pharmaceutical companies should assess themselves and provide detailed and clear pharmacoeconomic
analysis of these products so that mAbs may become less restricted, reimbursement may be granted to additional patient
groups, the rate of uptake enhanced and the potential revenue generated increased," he adds.


Estimated at USD 1.47 billion in 2004, Frost & Sullivan expects the total European monoclonal antibody therapeutics market to
grow at a compound annual growth rate (CAGR) of 34.1 per cent to amass USD 11.4 billion in 2011. There are currently ten
products commercially available in Europe including Remicade, Zevalin, Campath, Herceptin, Rituxan, Simulect, Zenapax
Synagis, ReoPro and the fully human mAb Humira. While chimeric mAbs currently control the market, humanised and human mAbs
are expected to dominate in future.


Over the next four to five years, oncology and AIID are projected to be the primary areas of commercial focus. Oncology is
likely to remain the leading revenue generator with sales of approximately USD 6.5 billion forecast in 2011. AIID indications
are set to follow with estimated sales of USD 4.5 billion in 2011. Other indication areas such as cardiovascular disorder,
organ transplantation and infectious diseases are likely to show less encouraging growth.


As competition intensifies, strategic alliances between mAb developers and big pharmaceuticals companies are accelerating
market growth. To capitalise on rising demand, the pharmaceutical and biotechnology industry will need to continue to evolve
towards technology integration and market expansions, even as they work towards offering competitive pricing, developing
holistic solutions - from diagnosis to treatment to after care and providing technical and efficient customer care.


"Success will depend on a medley of key factors including innovative molecular engineering, shorter development times, higher
success rates, robust and efficient intellectual property (IP) protection and development of cost-effective manufacturing,"
concludes Dr. Adhikari.


If you are interested in an analysis overview providing an introduction into the European Monoclonal Antibodies Therapeutics
Market - then send an email to Katja Feick -Corporate Communications at katja.feickfrost with the following
information: Full name, Company Name, Title, Contact Tel Number, Email. Upon receipt of the above information, an overview
will be emailed to you.


The European Monoclonal Antibodies Therapeutics Market

Code: B421-52


Background

Frost & Sullivan, an international growth consultancy, has been supporting clients' expansion for more than four decades. Our
market expertise covers a broad spectrum of industries, while our portfolio of advisory competencies includes custom
strategic consulting, market intelligence, and management training. Our mission is to forge partnerships with our clients'
management teams to deliver market insights and to create value and drive growth through innovative approaches. Frost &
Sullivan's network of consultants, industry experts, corporate trainers, and support staff spans the globe with offices in
every major country.


Media Contacts:


Europe:

Katja Feick

Corporate Communications

P: +44 (0) 20 7915 7856

F: +44 (0) 20 7730 3343

E: katja.feickfrost


Americas:

Danielle White

Corporate Communications

North America Team Leader

P: 210.247.2403

F: 210.348.1003

E: dwhitefrost


APAC:

Radhika Menon Theodore

Corporate Communications

P: +91 44 24314263 Ext:312

E: rmtheodorefrost


India:

Surbhi Dedhia

Corporate Communications

P: +91 22 2832 4705 Ext: 131

E: sdedhiafrost


List of key industry participants: Abbott Laboratories, Alexion Pharmaceuticals Inc., Amgen Inc., Antisoma Plc, Biogen Idec,
Bristol-Myers Squibb, Cambridge Antibody Technology, Celltech Group plc, Centocor Inc., Chugai Pharmaceutical Co. Ltd, Corixa
Corporation, Elan Corporation plc, Eli Lilly and Company, Genentech Inc., Genmab A/S, Genzyme Corporation, GlaxoSmithKline,
IDEC (Biogen), Immuno-Designed Molecules (IDM), ILEX Oncology, ImClone Systems Incorporated, Immunex (Amgen), Immunomedics
Inc., Johnson & Johnson, Medarex Inc., MedImmune Inc., Merck KGaA, Millenium Pharmaceuticals Inc., Novartis AG, Pfizer Inc.,
Pharmacia (Pfizer Inc.), Protein Design Labs Inc., Roche, Schering-Plough Corporation, Serono S.A., Wyeth, XOMA


View drug information on Campath; Herceptin; Humira.

News From The Journals Of The American Society For Microbiology

New Vaccine That Protects Monkeys Against Avian Flu Ready for Human Trials



Researchers from the National Institutes of Health and University of Maryland report that a new vaccine that protects monkeys against the avian influenza virus is now a candidate for clinical trial in humans. They report their findings in the November 2007 issue of the Journal of Virology.



The rate of transmission of the highly pathogenic avian influenza virus (HPAIV) from birds to humans is rapidly increasing. The H5N1 strain is responsible for 278 known human infections resulting in 168 deaths. The possibility of a pandemic outbreak emphasizes the need for an effective vaccine, however development has been impeded by factors such as poor immunogenicity, biosafety concerns, and risk of genetic exchange with circulating influenza virus strains.



In the study researchers developed a live vaccine incorporating the avian Newcastle disease virus (NDV), which expresses a common gene found in the H5N1 avian influenza virus, and tested it in African monkeys. The vaccine was administered both intranasally and through the respiratory tract in two doses with a 28-day interval in between. Response after one dose showed low amounts of virus shedding indicating protection. Following two doses, high levels of neutralizing antibodies were present in all immunized monkeys. A substantial response to either dosage was noted in the respiratory tract indicating a likely reduction in transmission in the event of an outbreak.



"In this study, we have developed a vaccine candidate, NDV-HA, for immunization against H5N1 HPAIV and have tested it in a nonhuman primate model," say the researchers. "The vaccine was well tolerated and induced substantial local and systemic immune responses, demonstrating that NDV has potential as a live virus candidate vaccine against HPAIV."



(J.M. DiNapoli, L. Yang, A. Suguitan Jr., S. Elankumaran, D.W. Dorward, B.R. Murphy, S.K. Samal, P.L. Collins, A. Bukreyev. 2007.

Immunization of primates with a Newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus.
Journal of Virology, 81. 21: 11560-11568.)



Researchers Identify a Promising New Class of Inhibitors Against West Nile Virus



Researchers from the Washington University School of Medicine have identified a new class of compounds that may inhibit West Nile virus in humans. They report their findings in the November 2007 issue of the Journal of Virology.



West Nile virus (WNV), a member of the flavivirus family which also includes dengue virus and yellow fever virus, can cause disease in humans, horses, and other vertebrate species when transmitted by infected mosquitoes. WNV has been confirmed in all 48 continental United States as well as Canada, Mexico, the Caribbean and South America and the fatality-to-case ratio calculated from recent outbreaks is 4 to 14%. There were 24,000 human cases diagnosed between 1999 and 2006 and currently there is no vaccine or therapeutic treatment approved for use in humans.
















In the study researchers screened 80,000 small molecule compounds from a commercial library for their ability to inhibit WNV replication. They identified 10 compounds with strong inhibitory responses toward diverse WNV isolates. Many of these compounds had not been previously marked as inhibitory prospects against WNV or other related or unrelated viruses. In addition several of the compounds also showed inhibition capabilities against dengue and yellow fever viruses.



"Overall, these compounds comprise a novel class of promising inhibitors for therapy against WNV and other flavivirus infections in humans" say the researchers.



(A.O. Noueiry, P.D. Olivo, U. Slomczynska, Y. Zhou, B. Buscher, B. Geiss, M. Engle, R.M. Roth, K.M. Chung, M. Samuel, M.S. Diamond. 2007.

Identification of novel small-molecule inhibitors of West Nile virus infection.
Journal of Virology, 81. 21: 11992-12004.)



New Study Suggests Many Unknown Microbes in Soil



Metagenomic analysis of microbial biodiversity in soil samples suggest that non-bacterial species greatly outnumber bacterial species. This means the majority of microorganisms on the Earth remain undiscovered, according to researchers from the University of Colorado, University of South Florida, San Diego State University and Duke University. They report their findings this month in the journal Applied and Environmental Microbiology.



Soil microorganisms represent a significant portion of living matter on Earth and play a key role in ecosystem functions. Bacteria, fungi, archaea and viruses are the four microbial groups currently known to man. Bacterial presence in soil has been the most extensively studied, however with the environment at the forefront of worldwide focus, expanded research on fungal, archaeal, and viral communities is much needed.



In the study researchers used an RNA-based analysis technique to examine the richness of bacteria, fungi, archaea, and viruses in samples collected from prairie, desert, and rainforest soils. These sites were specifically targeted because they represent globally dominated ecosystem types and are broad in aridity and productivity. Results showed that unique archaeal or fungal units appeared to rival or exceed unique bacterial units in each of the soil samples.



"In this first study, to comprehensively survey rival communities using a metagenomic approach, we found that soil viruses are taxonomically diverse and distinct from the communities of viruses found in other environments that have been surveyed using a similar approach," say the researchers. "Within each of the four microbial groups, we observed minimal taxonomic overlap between sites, suggesting that soil archaea, bacteria, fungi, and viruses are globally as well as locally diverse."



(N. Fierer, M. Breitbart, J. Nulton, P. Salamon, C. Lozupone, R. Jones, M. Robeson, R.A. Edwards, B. Felts, S. Rayhawk, R. Knight, F. Rohwer, R.B. Jackson. 2007.
Metagenomic and small-subunit rRNA analyses reveal the genetic diversity of bacteria, archaea, fungi, and viruses in soil.
Applied and Environmental Microbiology, 73. 21: 7059-7066.)







Source: Carrie Patterson


American Society for Microbiology

Sackler Prize In Biophysics To Be Presented To Protein Folding Researcher David Baker And His Team

Dr. David Baker, University of Washington (UW) professor of biochemistry and an investigator at the Howard Hughes Medical Research Institute, has been selected to receive the 2008 Raymond & Beverly Sackler International Prize in Biophysics, along with Dr. Martin Gruebele of the University of Illinois, Urbana-Champaign, and Dr. Jonathan Weissman of the University of California, San Francisco.



The field for this year's prize was the physics of structure formation and self-assembly of proteins and nucleic acids. The award will be presented to the three scientists Dec. 15 at Israel's Tel Aviv University.



The prize was established by arts and sciences philanthropists Dr. Raymond R. Sackler and his wife, Beverly Sackler. Raymond Sackler is a psychiatrist and co-founder of a multinational pharmaceutical company.



Baker is being honored for his seminal contributions to computer-based studies of the manner and the speed in which chains of amino acids fold into protein molecules. Anyone who has tried to put together a cardboard box knows the importance of proper folding to get a useful product. The same is true when the body manufactures proteins.



Creating computer models of protein-folding is essential for figuring out how genetic information directs protein formation, how proteins work, and how misfolded, misshapen, and malfunctioning proteins might underlie serious degenerative diseases.



Baker has developed computer programs to predict protein structures from amino acid sequences in DNA. His program, Rosetta, is among the most accurate. He has combined data from nuclear magnetic resonance imaging and X-ray defraction imaging with his computer modeling to more quickly delineate protein molecule structures. He also researches the ways that molecular configurations of proteins determine their functions in biochemical reactions.



In addition, Baker and his team have developed new protein folds and have designed and built functional enzymes, and engineered protein interactions, that previously did not exist in nature. His group has also contributed new ways of studying proteins in membranes -- the thin fatty covering that separates the inside of the cell from the external environment. These transmembrane proteins include molecular channels that permit the flow of calcium into and out of the cell, and that are responsible for the passage of neural impulses and communication between cells. The Baker group was able to apply the Rosetta program to these unusual proteins by treating the membranes as a series of layers with different protein folding requirements.



Baker has involved people of all ages and backgrounds from around the world in helping with protein folding research. People donate their idle computer time to a project called Rosettahome ( boinc.bakerlab/rosetta/). The combined computing power of thousands of home computers around the globe (called "distributed computing") allows for lengthy, complicated analysis of the data needed to study how proteins are assembled. Watch a YouTube video on Rosettahome: ie.youtube/watch?v=GzATbET3g54







Baker and his team have also created Fold-It, a Web-based protein folding and design game ( fold.it/portal/ )for scientists and non-scientists alike to play to study protein formation. Players compete to be the best in the world at folding and designing proteins. More than 20,000 players have downloaded the game. In another aspect of his work, Baker collaborates with scientists at more than 10 universities to continually update and extend the Rosetta program, thereby creating a scientific commons to freely share research data on protein folding.



Baker and his community's discoveries have led to many practical applications in efforts to design new medications and molecular therapies and in other fields that rely on the structural mechanics of proteins.



Source: Leila Gray

University of Washington

First Clinical Trial Of Apatone For Cancer Treatment Completed By Researchers

In a significant advancement in the ongoing battle against cancer, a group of researchers from Summa Health System, IC-MedTech and other institutions have completed the first ever FDA-approved human clinical trial of Apatone®. Demonstrating promising results, Apatone exploits a new strategy to selectively lower the level of compounds within tumor cells that assist in energy production and protect against chemotherapy. This non-toxic approach weakens and kills cancers in a novel way.



Apatone was discovered by Dr. Henryk Taper from the Catholic University of Leuven in Brussels, Belgium and was developed by Dr. James Jamison and Dr. Jack Summers, both of Summa Health System, and Dr. Jacques Gilloteaux, now with the American University of the Caribbean in St. Maarten. Their groundbreaking discovery found that moderate doses of Apatone eliminate many types of cancer cells, including prostate, bladder, renal and ovarian.



"This strategy targets cancer cells by their inflammatory response," explains Dr. Jamison. "It's a different approach than most other anti-tumor drugs, which target dividing cells or the development of blood vessels within the tumor. Since normal cells use sugars or fats for energy and cancer cells rely on glucose, the real key here is that Apatone resembles glucose. As Apatone preferentially accumulates in cancer cells, it also supplies quinone that weakens and can destroy the cancer cell from within.



"The bottom line is: Apatone selectively targets and kills tumor cells using non-toxic biochemistry that protects surrounding healthy tissue."



Licensed in 2004 to IC-MedTech, Inc., a California-based biotechnology company, the first clinical trial began in 2005 to evaluate the drug in prostate cancer patients. The clinical studies, which were conducted at Summa Health System in Akron, Ohio and with Dr. Ananias Diokno at William Beaumont Hospital in Royal Oak, Mich., examined the safety and effectiveness in 17 end-stage prostate cancer patients for 12 weeks. These patients took Apatone orally each day. The trials were supported by the Beaumont Foundation, Summa Health System and IC-MedTech.



Throughout the trial, investigators monitored prostate-specific antigen (PSA) levels, PSA velocity and PSA doubling times. Although PSA is a protein normally produced by the prostate gland, individuals with prostate cancer have increased levels. PSA velocity is the change of PSA levels over time and PSA doubling time is the time it takes for a patient's PSA level to double.



"The results of the trial are very promising," said Dr. Jamison. "Sixteen of the 17 patients responded positively to the Apatone and 13 showed a decrease in PSA velocity and an increase in PSA doubling time. At the end of the treatment period, 15 patients opted to continue treatment."
















Showing delays in the biochemical progression in end-stage prostate cancer patients, the trial successfully demonstrated the safety and efficacy of orally administered Apatone. Research is continuing and insights into how this drug works have lead to collaborations and discoveries in the field of liquid crystal compounds. Apatone is a Liquid Crystal PharmaceuticalTM and has resulted in research sponsored at Summa and with Dr. Chun-che Tsai at Kent State University. This work shows great promise for cancer and other diseases.



"Ultimately, Apatone is intended to be administered intravenously prior to chemotherapy so it can break down the substances in a tumor that protect it from the chemotherapy and allow a greater cell kill," continued Dr. Jamison. "Between cycles and following completion of chemotherapy, Apatone will be taken orally to help prevent or slow tumor regrowth."



Although the researchers are still working to receive FDA approval for chemotherapy in conjunction with Apatone, the FDA granted orphan drug status to IC-MedTech this year for the use of Apatone as treatment for metastatic, or locally advanced, stage III and IV bladder cancer. An orphan drug designation grants special status to a product to treat a rare disease or condition.



Additional clinical trials are planned for intravenous administration of Apatone in patients who have failed chemotherapy.






About Summa Health System



Summa Health System is one of the largest organized delivery systems in Ohio. Encompassing a network of hospitals, community health centers, a health plan, a physician-hospital organization, research and a foundation, Summa is nationally renowned for excellence in patient care and for exceptional approaches to health care delivery. Summa's clinical services are consistently recognized by U.S. News and World Report and Solucient. For more information, visit summahealth/.



Source: Julie Uehara


Summa Health System

Mutations, Low Growth And Fertility Among Crustaceans In Sydney Harbor Tributary Linked To Heavy Metal

Heavy metal pollutants are linked to genetic mutations, stunted growth and declining fertility among small crustaceans in the Parramatta River, the main tributary of Sydney Harbour, new research shows.



The finding adds to mounting evidence that toxic sediments and seaweeds in Sydney Harbour are a deadly diet for many sea creatures.



The new findings, published in the journal, Science of the Total Environment, reveal genetic mutations among crustaceans (Melita plumulosa) in the Parramatta River but none among those in the cleaner Hawkesbury River.



Earlier this year, UNSW scientists revealed that copper-contaminated seaweeds in Sydney Harbour were killing 75 percent of the offspring of small crustaceans that feed on a common brown seaweed.



That study showed that the harbour's seaweeds have the world's highest levels of copper and lead contamination as a consequence of stormwater run-off, industrial wastewaters and motorised watercraft.



The new study found the mutations and lower growth and fertility persisted through several generations of M. plumulosa in controlled laboratory conditions, suggesting that genetic changes are causing permanent negative impacts.



"The lower fertility and growth rates among the creatures exposed to contaminants is probably a stress response," says the study's lead author, UNSW science honours student, Pann Pann Chung.



The crustaceans were randomly sampled from two sites within each river: Homebush Bay South and Duck River in the Parramatta River, and Mooney Mooney and Half Moon Bend in the Hawkesbury.



M. plumulosa is a shrimp-like creature found among rocks and mudflats on shorelines and tide zones, although little is known about its genetic history. A native to the south-eastern coast of Australia, the amphipod feeds on organic material in sand and sediment.



"These crustaceans are sensitive to heavy metals such as copper, cadmium and zinc and scientists use them as a 'test organisms' for assessing the toxicity of marine sediments, says Ms Chung. "They accumulate heavy metals inside their tissues and scientists use them to monitor environmental pollutants."



Other research has revealed that chronic exposure to metal toxicants is linked to DNA damage in earthworms, periwinkles and some fish species.







Source: Dan Gaffney


University of New South Wales

Men Under Stress Find Their Thinking Disrupted

A new neuroimaging study on stressed-out students suggests that male humans, like male rats, don't do their most agile thinking under stress. The findings, published this month in the Proceedings of the National Academy of Sciences, show that 20 male M.D. candidates in the middle of preparing for their board exams had a harder time shifting their attention from one task to another than other healthy young men who were not under the gun.



Previous experiments had found that stressed rats foraging for food had similar impairments and that those problems resulted from stress-induced changes in their brain anatomy. The new study, using functional magnetic resonance imaging (fMRI) to scan the stressed students' brains, is a robust example of how basic research in an animal model can lead to high-tech investigations of the human brain.



"It's a great translational story," says Bruce S. McEwen, head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at The Rockefeller University, who worked on the project with colleagues at Weill Cornell Medical College. "The research in the rats led to the imaging work on people, and the results matched up remarkably well."



The work holds good news too, for both rats and humans: Their brains recuperate quickly. Less than a month after the stress goes away, they are back to normal. "The message is that healthy brains are remarkably resilient and plastic," McEwen says.



To probe the effects of stress, the researchers scanned the brains of volunteers, some stressed and others relatively relaxed, performing two subtly different kinds of mental tasks, either an attention-shift or a response-reversal. Lying inside the scanner, the subjects looked at two discs: one red and one green, with one moving up and the other down. In a series of trials, they were prompted to choose a disc according to motion or color. By ordering when the subjects did which tasks, they challenged their volunteers' brains to either switch focus from color to motion, or to suddenly reverse their choice of a disc in the same category.



"It's like the old story about the American crossing the road in England," says Conor Liston, an M.D.-Ph.D. student at Rockefeller and Cornell, who led the research. A response-reversal requires the brain to override the habitual impulse to first look left instead of right for oncoming cars. An American in Venice might require an attention-shift, by contrast, to seek out boats instead of evading cars.



In earlier research on rats, neuroscientists found that these two tasks place demands on different circuits in the brain, and the circuits are affected in different ways by stress. In particular, collaborative work by McEwen and John Morrison at Mount Sinai Medical Center have shown that repeated stress on rats shriveled nerve cells of the medial prefrontal cortex, and that a shrunken prefrontal cortex is linked to slower performance on attention-shifting tasks. In those experiments, rats learned to dig through a certain texture, like sawdust, in the presence of an irrelevant odor to find food; then the researchers made odor, rather than texture, the clue for finding the food and measured how long it took the rats to switch their foraging strategies. But while the restricted prefrontal cortex - a larger version of which is thought to play a role in the "executive function" in humans - slowed the rats' performance on attention-shifts, it did not change their performance on response-reversal tasks. In fact, neurons in a different part of the brain thought to be involved in response-reversals, the orbital frontal cortex, actually grew larger from the stress.
















The new research suggests that something very similar may happen to distressed humans. Liston, working with B.J. Casey at the Sackler Institute at Weill Cornell, used fMRI to explore his hunch that the brains of rats and men have some basic processes in common - that stress would also impair performance on attention-shifting tasks and diminish activity in the medial prefrontal cortex.



He found that male med students who said they were stressed out one month before they were to take their boards fared much worse on attention-shifting tasks than similar healthy adults who claimed to be taking it easy. The high stress levels, gauged by an established measure called the perceived stress scale, were also tightly associated with diminished activity in the prefrontal cortex. But their performance on response-reversals was unimpaired. Finally, as was found in the rats, when Liston scanned the students again one month after the test, he discovered that their attention-shifting performance had returned to normal along with their brains.



The uncanny similarities surprised even the researchers. "I certainly don't want to say that rat brains are just like human brains," Liston says. "But it does show that you can use research in animal models to help interpret human neuroimaging results."



Liston plans to next explore how stress impacts the rest of the brain. He also wants to investigate whether or not there are differences in how the brains of men and women respond to stress. "Stress is doing a whole lot of things in your brain that we don't understand yet, but we know that it is intimately involved in a wide range of neuropsychiatric disorders," Liston says. A mechanistic understanding of stress could lead to insights into associated psychiatric problems, he says.








Proceedings of the National Academy of Sciences online: January 12, 2009



Source: Brett Norman


Rockefeller University

"Singing" Mice - The Ongoing Debate Of Nature Versus Nurture

What happened to being "quiet as a mouse"? Researchers have recently shown that, rather than being the silent creatures of popular belief, mice emit ultrasonic calls in a variety of social contexts, and these calls have song-like characteristics.So if mice sing, where do they get their music? Are they born with the songs fully formed in their heads, or do they learn them from their peers? This question is of great interest to scientists as, while many organisms produce genetically regulated vocalizations, only a select few species (such as ourselves) can actually learn these vocalizations. If it turns out that mice can indeed learn new songs, it would provide a very convenient mammalian model of vocal learning.



Whether or not mouse song involves learning either through auditory imitation or behavioral feedback (e.g., from the mother), however, is a subject of hot debate, and the answer is proving elusive. To highlight the difficulties facing researchers, two studies published on March 9, 2011 in the open-access journal PLoS ONE have come to differing conclusions about whether mouse vocalization patterns are innate or learned.



In the first study, researchers from Northeastern Ohio Universities Colleges of Medicine and Pharmacy and the MRC Institute of Hearing Research conducted a study to understand developmental changes in mouse song that would allow parents to distinguish older mice from younger mice. They found that many features of mouse song changed with age. For example, the pattern of syllables within songs became more complex.



According to lead author Jasmine Grimsley, "We concluded that the increased complexity of song suggeststhat mice may be capable of vocal learning, but we also recognized that other factors besides learning, such as genetically controlled neuromuscular development, might explain the increased complexity. We conducted our study in normal hearing, CBA/CaJ mice, and we intend to use the results to understand how the brain codes the meaning of these sounds."



The second study, a collaboration among Azabu University, the RIKEN Brain Science Institute, and the Okanoya Emotional Information Project used a cross-fostering experiment to test whether the vocalization patterns were more strongly influenced by genetics or environment. The researchers used males from two mouse strains, C57BL/6 and BALB/c, which emit different vocalizations. Males from each strain were raised in litters of the opposite strain until weaning. Vocalization patterns were recorded at 10-20 weeks of age, and the researchers compared vocalizations of cross-fostered mice to control mice reared by genetic parents.



According to first author Takefumi Kikusui, "We first showed that two strains of mice, BALB and B6, sing strain-unique song types. We then showed that rearing BALB by B6 parents do not change the BALB characteristics of the song, and vise-versa. The fact that the cross-fostered animals sang songs similar to those of their genetic parents suggests that the structure of this courtship sound is under strong genetic control."
















When asked about the results from the other study, corresponding author Dr. Kazuo Okanoya noted that, "they demonstrate substantial developmental changes in social vocalizations with age. They also characterized complex behavioral phenotypes of mice vocalizations. However, in our opinion, developmental and phonotypical complexities of mice vocalizations are not related with whether or not the vocalizations are learned."



Dr. Grimsley said of the Japanese research, "while we believe that the study by Kikusui et al. indicates that some aspects of mouse songs are genetically driven, the conclusion that vocal learning does not occur in mice is too strong for the experiments that they performed. In our opinion, the jury is still out regarding whether mice do, or do not, exhibit vocal learning."



Which is it then, nature or nurture? It appears that it is still too early to say for sure, and we do not yet know whether the mating songs of mice are genetically determined or learned from their parents. What is certain, however, is that even carefully performed scientific research does not always produce straight-forward answers.



Funding: The work was supported by NIH R01-DC000937-20 and DC000937-18S1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.


Citation:


"Development of Social Vocalizations in Mice"

Grimsley JMS, Monaghan JJM, Wenstrup JJ (2011)

PLoS ONE 6(3): e17460. doi:10.1371/journal.pone.0017460







Funding:
This research was supported by Japan Society for the Promotion of Science (T.K. and R.N.), the Promotion and Mutual Aid Corporation for Private Schools of Japan, Grant-in-Aid for Matching Fund Subsidy for Private Universities (T.K.), RIKEN Brain Science Institute (K.O.), and by ''Exploratory Research for Advanced Technology, Okanoya Emotional Information Project'' (K.O.) from Japan Science and Technology Corporation. Funders paid for experimental supplies and personnel cost for this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.



Competing Interests: The authors have declared that no competing interests exist.


Citation:


"Cross Fostering Experiments Suggest That Mice Songs Are Innate"

Kikusui T, Nakanishi K, Nakagawa R, Nagasawa M, Mogi K, et al. (2011)

PLoS ONE 6(3): e17721. doi:10.1371/journal.pone.0017721

Suppressing Disease-Causing Genes Is Now Within Reach

Mount Sinai researchers have developed a new gene silencing technology that could be used to target genes that can lead to the development of certain diseases. This technology could pave the way for preventing diseases where gene dysfunction plays a role. The groundbreaking research was led by Ming-Ming Zhou, Ph.D., Professor and Chairman of the Department of Structural and Chemical Biology at Mount Sinai School of Medicine. The findings, which will be published in the September issue of Nature Cell Biology, are available on the magazine's web site.



"By being able to silence certain genes, we may be able to suppress genes that can cause diseases such as HIV/AIDS, cancer, inflammation and diseases of the central and peripheral nervous systems. We now know we can focus on these genes and potentially change the ultimate course of many diseases that have a major impact on people's lives," says Dr. Zhou.



In the study, Dr. Zhou, Shiraz Mujtaba, Ph.D., Assistant Professor of Structural and Chemical Biology at Mount Sinai and their colleagues discovered that Paramecium bursaria chlorella virus uses a viral protein to modify host DNA packing chromatin and switch host transcription machinery for viral replication. Based on this finding, researchers were able to develop a new gene targeting technology that effectively suppresses transcriptional expression of targeted genes in human cells, including genes that are linked to the onset of a number of diseases.







About The Mount Sinai Medical Center



The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation's oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 50,000 people were treated at Mount Sinai as inpatients, and there were nearly 450,000 outpatient visits to the Medical Center. Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic-science research, as well as having an innovative approach to medical education. With a faculty of more than 3,400 in 38 clinical and basic science departments and centers, Mount Sinai ranks among the top 20 medical schools in receipt of National Institute of Health (NIH) grants.



Source: Mount Sinai Press Office


The Mount Sinai Hospital / Mount Sinai School of Medicine

Plastic Antibody Works In First Tests In Living Animals

Scientists are reporting the first evidence that a plastic antibody - an artificial version of the proteins produced by the body's immune system to recognize and fight infections and foreign substances - works in the bloodstream of a living animal. The discovery, they suggest in a report in the Journal of the American Chemical Society, is an advance toward medical use of simple plastic particles custom tailored to fight an array of troublesome "antigens." Those antigens include everything from disease-causing viruses and bacteria to the troublesome proteins that cause allergic reactions to plant pollen, house dust, certain foods, poison ivy, bee stings and other substances.



In the report, Kenneth Shea, Yu Hosino, and colleagues refer to previous research in which they developed a method for making plastic nanoparticles, barely 1/50,000th the width of a human hair, that mimic natural antibodies in their ability to latch onto an antigen. That antigen was melittin, the main toxin in bee venom. They make the antibody with molecular imprinting, a process similar to leaving a footprint in wet concrete. The scientists mixed melittin with small molecules called monomers, and then started a chemical reaction that links those building blocks into long chains, and makes them solidify. When the plastic dots hardened, the researchers leached the poison out. That left the nanoparticles with tiny toxin-shaped craters.



Their new research, together with Naoto Oku's group of the University Shizuoka Japan, established that the plastic melittin antibodies worked like natural antibodies. The scientists gave lab mice lethal injections of melittin, which breaks open and kills cells. Animals that then immediately received an injection of the melittin-targeting plastic antibody showed a significantly higher survival rate than those that did not receive the nanoparticles. Such nanoparticles could be fabricated for a variety of targets, Shea says. "This opens the door to serious consideration for these nanoparticles in all applications where antibodies are used," he adds.



Article:

"Recognition, Neutralization, and Clearance of Target Peptides in the Bloodstream of Living Mice by Molecularly Imprinted Polymer Nanoparticles: A Plastic Antibody"



Full text article.



Source:

Michael Bernstein

American Chemical Society