Academia Should Fulfill Social Contract by Supporting Bioscience Startups, Case Study Says

Universities not only provide the ideal petri dish for cultivating bioscience with commercial potential, but have a moral obligation to do so, given the opportunity to translate public funding into health and jobs, according to a new case study by UCSF researchers.

In an analysis published Wednesday in Science Translational Medicine, researchers at the California Institute for Quantitative Biosciences (QB3) assessed the impact of the institute’s efforts over the past eight years in supporting entrepreneurs on the three UC campuses in which it operates: UCSF, UC Berkeley and UC Santa Cruz.

The study found that, by lowering the hurdle even very slightly for scientists to become entrepreneurs, the scientists were able to gain extraordinary traction in translating academic research into public benefit, generating 60 new companies in the first six years and attracting 75 new bioscience entrepreneurs in the last year alone.
“This fundamentally changes the way we think of academic science,” said Douglas Crawford, PhD, assistant director of QB3 and senior author on the paper. “There is a distressing paucity of new drugs in the pipeline and a clear need for new economic engines in this country. This is a call to action to address that.”
The paper cites the following essential support that universities can provide:

• Bioscience-focused incubators
• An open network approach that enables any entrepreneur to participate
• Competitive seed funding options
• Real-world mentoring that gives scientist a clear sense of market needs.

At UCSF, this support is happening on multiple fronts, starting with the efforts underway at QB3, which focus on supporting entrepreneurs directly. UCSF also is home to the National Institute of Health's first Clinical and Translational Sciences Institute (CTSI), which has become a model nationwide in creating a vast network of scientists in both clinical and basic research, in an effort to improve collaboration between them and expedite translational research to improve health. CTSI also is developing broad coalitions and partnerships at the local and national levels to enable a transformation of the research environment. In addition, UCSFs' office of Innovation, Technology and Alliances is a leader nationwide in supporting entrepreneurship on campus, while forging direct collaborations with industry.

Growing Incubators of Bioscience Companies

In the first six years since QB3 started supporting entrepreneurs at the UCSF Mission Bay campus, its growing network of incubators helped launch 60 new bioscience companies at UCSF and across the San Francisco Bay at UC Berkeley — at a cost of $1 million per year. Of those, 56 are still in business, and 13 have moved beyond the incubator network or have been purchased by larger companies.
Together, those companies have created more than 280 jobs and attracted more than $230 million in either small business grants or venture capital funding for those companies, which are primarily focused on developing therapeutics, medical devices and research tools. That’s a 38-fold return on investment, despite current negative trends in seed-stage investing, in addition to the public benefit of any products those companies generate.


The federal government invests $50 billion per year in academic research, including $23 billion for life sciences from the National Institutes of Health (NIH) alone, according to the paper. Both Baltimore, which is home to universities, and the San Francisco Bay Area receive about $2 billion annually in government research and development funding, yet productivity as measured by high-tech startups was 20-fold higher in the San Francisco area than Baltimore, the analysis found.

(A) Regional differences in R&D spending. R&D spending by universities (left axis)
and number of companies listed in the Deloitte Technology Fast 500 (right axis) in
selected urban centers. Analysis by the Center for an Urban Future, prepared with
data from the National Science Foundation/Division of Science Resources
Statistics. (B) Growth of the QB3 Garage Network. Millions of dollars invested in
QB3 Garage Network companies each year (left axis), and number of new
start-ups that joined the QB3 Garage Network per year (right axis). (C) Number
and types of jobs created in the QB3 Garage Network.
CREDIT: C. BICKEL/SCIENCE TRANSLATIONAL MEDICINE

“This is clearly not an issue of how much funding is coming to the region. It’s an issue of how we think about our social contract,” said Regis B. Kelly, PhD, UCSF professor of biochemistry and biophysics, executive director of QB3 and a co-author on the paper. “Most people would say the public good a university offers is in providing research and education, but if we truly want to support the public with the benefits of science, we need to stop seeing economic growth and new medications as an inadvertent byproduct of academic research.”
Many U.S. universities, including UCSF, are exploring ways to work with the private sector, with the multiple goals of invigorating research on campus, expediting drug development and ultimately improving the therapies that make it to the market.
That’s a relatively new way of thinking, though, and one that often has been met with both skepticism and charges of conflicts of interest by those who believe science should be completely devoid of commercial influences.


“We have a fundamental charge as scientists to make an economic impact and to translate science into public benefit,” Crawford said. “That’s not a traditional way of thinking of universities, but at a certain point, we need to reassess that traditional thinking and take pride in the fact that a university’s public contributions extends beyond its classrooms.”
The paper points to the mission statement of the NIH, the nation’s largest bioscience funding agency, which specifically includes a goal “to enhance the Nation’s economic well-being and ensure a continued high return on the public investment in research.”
“So as academic scientists, we are actually paid to protect and improve health, to prevent disease, and to enhance economic well-being,” Crawford said. “This is not a sell-out to industry. It’s an obligation to society.”

Crawford emphasized that the goal of the analysis is not to assess blame, but to find solutions, and there are many. The authors also hope to generate discussion about which solutions work.




source : http://www.ucsf.edu/news/2012/10/13005/academia-should-fulfill-social-contract-supporting-bioscience-startups-case-study

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Whitehead scientists identify major flaw in standard approach to global gene expression analysis

The assumption in traditional genetic expression analysis that mRNA content is similar between cells (represented by orange and black dots) does not affect the final results when the cells in fact do have equivalent mRNA content, as in Figure A.  In Figure B, the cell represented by the orange dots has a significantly higher mRNA content, but when the data is normalized with the assumption that their contents are equal, the perceived response is skewed and inaccurately indicates that some of the genes are repressed (green bars).  Using a standardized control, as in Figure C, eliminates the assumptions about mRNA content and presents accurate results.

Whitehead Institute researchers report that common assumptions employed in the generation and interpretation of data from global gene expression analyses can lead to seriously flawed conclusions about gene activity and cell behavior in a wide range of current biological research.
“Expression analysis is one of the most commonly used methods in modern biology,” says Whitehead Member Richard Young. “So we are concerned that flawed assumptions may affect the interpretation of many biological studies.”
Much of today’s interpretation of gene expression data relies on the assumption that all cells being analyzed have similar total amounts of messenger RNA (mRNA), the roughly 10% of a cell’s RNA that acts as a blueprint for protein synthesis. However, some cells, including aggressive cancer cells, produce several times more mRNA than other cells. Traditional global gene expression analyses have typically ignored such differences.
“We’ve highlighted this common assumption in gene expression analysis that potentially affects many researchers,” says Tony Lee, a scientist in Young’s lab and a corresponding author of the article published in this week’s issue of Cell. “We provided a concrete example of the problem and a solution that can be implemented by investigators.”
Members of the Young lab recently uncovered the flaw while investigating genes expressed in cancer cells expressing high levels of c-Myc, a gene regulator known to be highly expressed in aggressive cancer cells.  When comparing cells with high and low c-Myc levels, they were surprised to find very different results using different approaches to gene expression analysis.  Further investigation revealed that there were striking differences in the total amounts of RNA from the high and low c-Myc -containing cells, yet these differences were masked by commonly used experimental and analytical methods.
“The different results we saw from different methods of gene expression analysis were shocking, and led us to reinvestigate the whole process on several platforms,” says Jakob Lovén, postdoctoral reseacher in Young’s lab and co-author of the Cell paper. “We then realized that the common assumption that cells contain similar levels of mRNA is badly flawed and can lead to serious misinterpretations, particularly with cancer cells that can have very different amounts of RNA.”
In addition to delineating this problem, the Whitehead scientists also describe a remedy. By using synthetically produced mRNAs, called RNA spike-ins, as standardized controls, researchers can compare experimental data and eliminate assumptions about total cell RNA amounts.  The remedy applies to all three gene expression analysis platforms they studied.
Although the researchers believe the use of RNA spike-ins should become the new standard for global gene expression analyses, questions are likely to persist about the interpretations of much prior research.
“There are over 750,000 expression datasets in public databases, and because they generally lack information about the cell numbers used in the analysis, it is unclear whether they can be re-examined in order to validate the original interpretation” says David Orlando, a scientist in the Young lab. “It may be necessary to reinvestigate some important concepts.”

source: http://wi.mit.edu/news/archive/2012/whitehead-scientists-identify-major-flaw-standard-approach-global-gene-expression

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A new glow for electron microscopy

In this electron microscope image of a mitochondrion, the matrix has
been stained with APEX, making it appear dark. The lighter
projections into the matrix represent the intermembrane space.
Image: Tom Deerinck and Jeff Martell

The glowing green molecule known as green fluorescent protein (GFP) has revolutionized molecular biology. When GFP is attached to a particular protein inside a cell, scientists can easily identify and locate it using fluorescence microscopy. However, GFP can’t be used with electron microscopy, which offers much higher resolution than fluorescence microscopy.

Chemists from MIT have now designed a GFP equivalent for electron microscopy — a tag that allows scientists to label and visualize proteins with unprecedented clarity.

“With things that may appear only a few pixels across by fluorescence microscopy — for example, a mitochondrion — you can’t make out any of the internal features. But with electron microscopy it’s very easy to discern the intricate internal structures,” says Jeff Martell, a graduate student in chemistry at MIT and lead author of a paper describing the new tag in the Oct. 21 online edition of Nature Biotechnology.

The new tag could help scientists pinpoint the locations of many cell proteins, providing new insight into those proteins’ functions, according to the researchers.

Improving on nature

Dubbed APEX, the new tag is similar to naturally occurring proteins that have been tried as imaging labels for electron microscopy. Horseradish peroxidase (HRP) is one commonly used tag, but it works only in a few compartments of a cell. Other recently developed tags work throughout a cell but are technically challenging to use because they require light to be shined on the sample and oxygen to be bubbled through it.

To improve on these methods, the researchers started with a protein similar to HRP, called ascorbate peroxidase (APX). APX is more versatile than HRP because it can function within a cell’s cytosol, in the main cavity of a cell.

Both HRP and APX belong to a class of enzymes called peroxidases, which remove an electron and a proton from other molecules in a process known as oxidation. Every peroxidase has different targets, and one of HRP’s main targets is a molecule called DAB, which when oxidized can be visualized with electron microscopy. The researchers genetically engineered APX so that it would also target DAB.

To use this new APEX tag (for “engineered APX”), the researchers deliver, into a living cell, a small ring of DNA containing the APEX gene joined to the gene for the protein they plan to image. The cell then produces the target protein, bound to the APEX protein.

Next, the researchers need to deliver DAB, which is not normally found in cells. This delivery takes place during the process of “fixing,” or stabilizing cells, which must be done before they can be imaged with electron microscopy.

When the APEX protein oxidizes DAB, it generates radicals that rapidly clump together into a tarlike polymer. That polymer can be detected through electron microscopy, allowing the researchers to pinpoint the location of the target protein.

A biological question resolved

To demonstrate the usefulness of their new tag, the researchers set out to resolve an open question regarding the location of a calcium channel protein discovered last year. Two research groups identified the protein and reported that it is located within mitochondria, but they had conflicting theories as to its precise location and orientation. Using the new imaging technique, the MIT-led team labeled the protein and determined that it is embedded in the inner mitochondrial membrane and faces into the innermost part of mitochondria, the mitochondrial matrix.

The team also showed that the new tag can label proteins throughout the cell — not only within mitochondria but also in the nucleus, the endoplasmic reticulum and the cytosol.

In current studies, the researchers are working on filling entire cells, such as neurons, with their imaging agent. This allows certain neurons in an electron microscope image to stand out, making it easier to trace the connections they make with other neurons.

“We want to find the exact connections that these cells are making, and APEX is a good way to label cells for electron microscopy. We can label specific types of cells and figure out how they fit into the neural circuitry,” Sanes says.


source : http://web.mit.edu/newsoffice/2012/a-new-glow-for-electron-microscopy-1021.html

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National Agri - Food Biotechnology Institute

Opportunity for research trainees are available at NABI, Mohali for 6 months starting from January to June 2013. The area of research training would be related to plant molecular biology, plant biotechnology, bioinformatics, nutrition biotechnology, and food biotechnology. Apart from lab works, each trainee has to involve in research field works and plant growth chambers for growing and testing research materials.

i) Eligibility : Pursuing M.Sc./M.Tech.

ii) Duration of training : 6 months (January to June 2013)

iii) Subject category for training :
                                                     A. Plant molecular biology
                                                     B. Plant biotechnology
                                                     C. Bioinformatics
                                                     D. Nutrition biotechnology
                                                     E. Food biotechnology


v) Application process :
In prescribed application format available on NABI website (http://www.nabi.res.in/Training.aspx) by post. The application should reach NABI on or before November 05, 2012 by 6:00 PM. The synopsis (available at http://www.nabi.res.in/Training.aspx) should be submitted by e-mail (trainee@nabi.res.in).

vi) The last date for application to reach NABI: November 05, 2012 by 6:00 PM

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Inernship in National Institute of Plant Genome Research

Applications are invited from suitable candidates for six months "Training Fellowship" in Bioinformatics under the BTISNET program of DBT in the Distributed Information Sub Center (DISC) facility at NIPGR, New Delhi, under the supervision of Dr. Gitanjali Yadav, Scientist, NIPGR.

Essential Qualification: Students currently pursuing the final year of Masters Degree (or equivalent) in Bioinformatics/Biotechnology with strong interest in Computational Biology and First class/division throughout academic career may apply.

Desirable Qualification: Proficiency in Coding Algorithms and Bioinformatics Applications, evidenced by short trainings or computing courses.

Application Deadline:October 27, 2012

Eligible candidates may apply by sending hard copy/E-mail of complete application together with the attested copies of qualifying certificates, in the given format along with a letter of recommendation from Head of the Department clearly mentioning the dates of training program. The applications should reach at the address given below within 15 days from the date of advertisement. The envelope must be superscribed by "Application for the Post of Trainee Fellow in the DBT project Distributed Information Sub center (DISC) under the supervision of Dr. Gitanjali Yadav, Scientist, NIPGR".

visit for further information http://www.nipgr.res.in/careers/vacancies_latest.php

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Scientists Pinpoint Key Player in Parkinson's Disease Neuron Loss

By reprogramming skin cells from Parkinson's disease patients with a known genetic mutation,
researchers at the Salk Institute for Biological Studies have identified damage to neural stem cells as a powerful player in the disease. The findings, reported online October 17th in Nature, may lead to new ways to diagnose and treat the disease.

The scientists found that a common mutation to a gene that produce the enzyme LRRK2, which is responsible for both familial and sporadic cases of Parkinson's disease, deforms the membrane surrounding the nucleus of a neural stem cell. Damaging the nuclear architecture leads to destruction of these powerful cells, as well as their decreased ability to spawn functional neurons, such as the ones that respond to dopamine.

The researchers checked their laboratory findings with brain samples from Parkinson's disease patients and found the same nuclear envelope impairment.

The Salk researchers found that a common genetic mutation
involved in Parkinson's disease deforms the membranes
(green) surrounding the nuclei (blue) of neural stem cells.
The discovery may lead to new ways to diagnose and treat the disease.

"This discovery helps explain how Parkinson's disease, which has been traditionally associated with loss of neurons that produce dopamine and subsequent motor impairment, could lead to locomotor dysfunction and other common non-motor manifestations, such as depression and anxiety," says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory, who led the research team. "Similarly, current clinical trials explore the possibility of neural stem cell transplantation to compensate for dopamine deficits. Our work provides the platform for similar trials by using patient-specific corrected cells. It identifies degeneration of the nucleus as a previously unknown player in Parkinson's."

Although the researchers say that they don't yet know whether these nuclear aberrations cause Parkinson's disease or are a consequence of it, they say the discovery could offer clues about potential new therapeutic approaches.

For example, they were able to use targeted gene-editing technologies to correct the mutation in patient's nuclear stem cells. This genetic correction repaired the disorganization of the nuclear envelope, and improved overall survival and functioning of the neural stem cells.

They were also able to chemically inhibit damage to the nucleus, producing the same results seen with genetic correction. "This opens the door for drug treatment of Parkinson's disease patients who have this genetic mutation," says Belmonte.

The new finding may also help clinicians better diagnose this form of Parkinson's disease, he adds. "Due to the striking appearance in patient samples, nuclear deformation parameters could add to the pool of diagnostic features for Parkinson's disease," he says.

The research team, which included scientists from China, Spain, and the University of California, San Diego, and Scripps Research Institute, made their discoveries using human induced pluripotent stem cells (iPSCs). These cells are similar to natural stem cells, such as embryonic stem cells, except that they are derived from adult cells. While generation of these cells has raised expectations within the biomedical community due to their transplant potential - the idea that they could morph into tissue that needs to be replaced - they also provide exceptional research opportunities, says Belmonte.

"We can model disease using these cells in ways that are not possible using traditional research methods, such as established cell lines, primary cultures and animal models," he says.

In this study, the researchers used skin fibroblast cells taken from Parkinson's disease patients who have the LRRK2 mutation, and they reprogrammed them to iPSC stem cells and developed them into neural stem cells.

Then, by using an approach to model what happens when these neural stem cells aged, they found that older Parkinson disease neural stem cells increasingly displayed deformed nuclear envelopes and nuclear architecture. "This means that, over time, the LRRK2 mutation affects the nucleus of neural stem cells, hampering both their survival and their ability to produce neurons," Belmonte says.

"It is the first time to our knowledge that human neural stem cells have been shown to be affected during Parkinson's pathology due to aberrant LRRK2," he says. "Before development of these reprogramming technologies, studies on human neural stem cells were elusive because they needed to be isolated directly from the brain."

Belmonte speculates that the dysfunctional neural stem cell pools that result from the LRRK2 mutation might contribute to other health issues associated with this form of Parkinson's disease, such as depression, anxiety and the inability to detect smells.

Finally, the study shows that these reprogramming technologies are very useful for modeling disease as well as dysfunction caused by aging, Belmonte says.


source: http://www.newswise.com/articles/salk-scientists-pinpoint-key-player-in-parkinson-s-disease-neuron-loss

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No Antibodies, No Problem

Researchers at the Johns Hopkins Bloomberg School of Public Health have determined a new mechanism by which the mosquitoes’ immune system can respond with specificity to infections with various pathogens, including the parasite that causes malaria in humans, using one single gene. Unlike humans and other animals, insects do not make antibodies to target specific infections. According to the Johns Hopkins researchers, mosquitoes use a mechanism known as alternative splicing to arrange different combinations of binding domains, encoded by the same AgDscam gene, into protein repertoires that are specific for different invading pathogens. The researchers’ findings were published October 18 in the journal Cell Host & Microbe and could lead to new ways to prevent the spread of a variety of mosquito born illnesses.

Mosquitoes and other insects use their primitive innate immune systems to successfully fight infections with a broad spectrum of viruses, bacteria, fungi and parasites, despite the lack of antibodies that are part of the more sophisticated human immune system. The effectiveness of the human immune system is to a large degree based on the ability to produce an enormous variety of antibodies containing different immunoglobulin domains that can specifically tag and label a pathogen for destruction. This great variety of pathogen-binding antibodies is achieved by combining different immunoglobulin gene segments and further mutate them through mechanisms called somatic recombination and hypermutation. While mosquitoes also have genes encoding immunoglobulin domains, they lack these specific mechanisms to achieve pathogen recognition diversity.

The Johns Hopkins researchers discovered a different way by which mosquitoes can combine immunoglobulin domains of a single gene called AgDscam (Anopheles gambiae Down Syndrome Cell Adhesion Molecule) to produce a variety of pathogen-binding proteins. The AgDscam gene is subjected to a mechanism called alternative splicing that combines different immunoglobulin domains into mature AgDscam proteins, depending on which pathogen has infected the mosquito. The researchers showed that this alternative splicing is guided by the immune signal transducing pathways (analogous to electrical circuits) that they previously demonstrated to activate defenses against different malaria parasites and other pathogens. While alternative splicing of the AgDscam gene does not nearly achieve the degree of pathogen recognition diversity of human antibodies, it does nevertheless vastly increase the variety of pathogen binding molecules.

“Using antibodies to fight infection is like fishing with a harpoon—it’s very targeted. The mosquito’s innate immune system is more like fishing with a net—it catches a bit of everything,” explained George Dimopoulos, PhD, senior investigator of the study and professor with the Johns Hopkins Malaria Research Institute. “However, we discovered that immune pathway-guided alternative splicing of the AgDscam gene renders the mosquito’s immune net, so to speak, more specific than previously suspected. The mosquito’s immune system can come up with approximately 32,000 AgDscam protein combinations to target infections with greater specificity.”

Dimopoulos and his group are developing a malaria control strategy based on mosquitoes that have been genetically modified to possess an enhanced immune defense against the malaria parasite Plasmodium. One obstacle to this approach is the great variety of Plasmodium strains that may interact somewhat differently with the mosquito’s immune system.

“Some of these strains may not be detected by the engineered immune system proteins that mediate their killing. Our new discovery may provide the means to create genetically modified mosquitoes that can target a broader variety of parasite strains, like casting a net rather than shooting with a harpoon,” said Dimopoulos.

 Malaria kills more than 800,000 people worldwide each year. Many are children.

“Anopheles NF-kB –Regulated Splicing Factors Direct Pathogen-Specific Repertoires of the Hypervariable Pattern Recognition Receptor AgDscam” was written by Yuemei Dong, Chris M. Cirimotich, Andrew Pike, Ramesh Chandra and George Dimopoulos.

source: http://www.jhsph.edu/news/news-releases/2012/dimopoulos_antibiodies.html

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Caltech Modeling Feat Sheds Light on Protein Channel's Function

Chemists at the California Institute of Technology (Caltech) have managed, for the first time, to simulate the biological function of a channel called the Sec translocon, which allows specific proteins to pass through membranes. The feat required bridging timescales from the realm of nanoseconds all the way up to full minutes, exceeding the scope of earlier simulation efforts by more than six orders of magnitude. The result is a detailed molecular understanding of how the translocon works.

The ribosome (red-blue) in complex with the translocon channel (green)
which is embedded in the cell membrane (yellow, white).
Proteins that are inserted via the ribosome into the channel can either be
laterally integrated into the cell membrane or secreted across the cell membrane (inset).

Modeling behavior across very different timescales is a major challenge in modern simulation research. "Computer simulations often provide almost uselessly detailed information on a timescale that is way too short, from which you get a cartoon, or something that might raise as many questions as it answers," says Thomas Miller, an assistant professor of chemistry at Caltech. "We've managed to go significantly beyond that, to create a tool that can actually be compared against experiments and even push experiments—to predict things that they haven't been able to s
ee."
The new computational model and the findings based on its results are described by Miller and graduate student Bin Zhang in the current issue of the journal Cell Reports.
The Sec translocon is a channel in cellular membranes involved in the targeting and delivery of newly made proteins. Such channels are needed because the proteins that are synthesized at ribosomes must travel to other regions of the cell or outside the cell in order to perform their functions; however, the cellular membranes prevent even the smallest of molecules, including water, from passing through them willy-nilly. In many ways, channels such as the Sec translocon serve as gatekeepers—once the Sec translocon determines that a given protein should be allowed to pass through, it opens up and allows the protein to do one of two things: to be integrated into the membrane, or to be secreted completely out of the cell.
Scientists have disagreed about how the fate of a given protein entering the translocon is determined. Based on experimental evidence, some have argued that a protein's amino-acid sequence is what matters—that is, how many of its amino acids interact favorably with water and how many clash. This argument treats the process as one in equilibrium, where the extremely slow rate at which a ribosome adds proteins to the channel can be considered infinitely slow.  Other researchers have shown that slowing down the rate of protein insertion into the channel actually changes the outcome, suggesting that kinetic effects can also play a role.
"There was this equilibrium picture, suggesting that only the protein sequence is really important. And then there was an alternative picture, suggesting that kinetic effects are critical to understanding the translocon," Miller says. "So we wondered, could both pictures, in some sense, be right? And that turns out to be the case."
In 2010 and earlier this year, Miller and Zhang published papers in the Proceedings of the National Academy of Sciences and the Journal of the American Chemical Society describing atomistic simulations of the Sec translocon. These computer simulations attempt to account for every motion of every single atom in a system—and typically require so much computing time that they can only model millionths of seconds of activity, at most. Meanwhile, actual biological processes involving proteins in the translocon last many seconds or minutes.
Miller and Zhang were able to use their atomistic simulations to determine which parts of the translocon are most important and to calculate how much energy it costs those parts to move in ways that allow proteins to pass through. In this way, they were able to build a simpler version of the simulation that modeled important groupings of atoms, rather than each individual atom. Using the simplified simulation, they could simulate the translocon's activity over the course of more than a minute.
The researchers ran that simplified model tens of thousands of times and observed the different ways in which proteins move through the channel. In the simulation, any number of variables could be changed—including the protein's amino-acid sequence, its electronic charge, the rate at which it is inserted into the translocon, the length of its tail, and more. The effect of these alterations on the protein's fate was then studied, revealing that proteins move so slowly within the tightly confined environment of the translocon that the pace at which they are added to the channel during translation—a process that might seem infinitely slow—can become important. At the same time, Miller and Zhang saw that other relatively fast processes give rise to the results associated with the equilibrium behavior.
"In fact, both equilibrium and kinetically controlled processes are happening—but in a way that was not obvious until we could actually see everything working together," Miller says.
Beyond elucidating how the translocon works and reconciling seemingly disparate experimental results, the new simulation also lets the researchers perform experiments computationally that have yet to be tried in the lab. For example, they have run simulations with longer proteins and observed that at such lengths—unlike what has been seen with shorter proteins—the equilibrium picture begins to be affected by kinetic effects.  "This could bring the two experimental camps together, and to have led that would be kind of exciting," Miller says.

source: http://www.caltech.edu/content/caltech-modeling-feat-sheds-light-protein-channels-function

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Eco-friendly Optics: Spider Silk’s Hidden Talents Brought to Light for Applications in Biosensors, Lasers, Microchips

Spiders use their silk to catch lunch. Now physicists are using it to catch light. New research shows that natural silk could be an eco-friendly alternative to more traditional ways of manipulating light, such as through glass or plastic fiber optic cables. Two teams independently exploring possible applications for the material’s photonic talents will present their latest breakthroughs at the Optical Society's (OSA) Annual Meeting, Frontiers in Optics (FiO) 2012, to be held next week in Rochester, N.Y.

A close-up view of a silk fiber taken
with scanning electron microscope.
Image courtesy of Nolwenn Huby.

Biomedical engineer Fiorenzo Omenetto of Tufts University in Boston will discuss his group’s work fabricating concoctions of proteins that make use of silk’s optical properties for implantable sensors and other biology-technology interfaces.
Physicist Nolwenn Huby at the CNRS Institut de Physiques de Rennes in France will talk about her team's use of pristine, natural spider silk to guide light through photonic chips—technology that could give birth to silk-based biosensors and medical imaging devices for use inside the body.
Both groups hope their work will lead to medical advancements that take advantage of the optical properties of silk. One of the strongest fibers in nature (the dragline used by spiders to form the structure of their webs is stronger, pound for pound, than steel), silk is biocompatible, biodegradable, and extremely hardy. Produced naturally by spiders and silkworms, it is a renewable resource. Added to these benefits is the more recent discovery that silk is a gifted manipulator of light, which can travel through silk almost as easily as it flows through glass fibers.
Though it may not be the best material in every one of these categories, the combination of talents is what makes silk such an attractive material to study, Omenetto explains. "There are materials that can do one of each, or a few of each," he says, "but seldom all of each."

Silk-based ‘plastics’ for implantable devices

A pristine silk fiber integrated into a photonic chip.
 The fiber connects three disks that can hold light.
 During the experiment, light is injected into one of
the disks and propagates along the silk to the other two.
 Image courtesy of Nolwenn Huby.

In their efforts to exploit silk’s optical merits, Omenetto’s team is developing silk-based materials that look like plastic, but retain the optical properties of pristine silk. One of the advantages of these materials is that they can degrade and be reabsorbed by the body. A sensor or tag made of silk protein could be implanted—at the site of a fractured bone, for example, to monitor healing—and merely left to dissolve. Once its purpose had been served, the silk tag would harmlessly fade away.
Omenetto is currently investigating a range of questions, from fundamental to commercial, and they go beyond implantable optics. His team recently won an INSPIRE grant from the National Science Foundation to create electronic components that are compostable. He has developed and tested a blue laser made from silk fiber-doped materials that is not only biodegradable but also uses less power to induce lasing than the acrylic materials that are commonly used. He is also exploring the possibilities of using silk to integrate a technological component with living tissue. "We’re thinking of how to scale up [production], how to interface with current technology," Omenetto says. He hopes some of the more "gadget-like" fruits of his labor will be commercially available within the next five to 10 years.

Guiding light with real silk

The golden orb web spider is common and, thanks
to its big size (6-10 cm), its silk can be extracted
easily.Image courtesy of Michel Pézolet.

Silk-doped composites are the subject of Omenetto's talk at FiO, but the optical merits of pristine silk will be the subject of Huby’s. Her team is experimenting with pure spider silk as a relatively inexpensive and ecologically friendly way to manipulate light within photonic chips.
As a light guide, silk works in a way comparable to the more commonly used glass microfibers that carry light within a chip; but silk comes out of the spider ready to use, whereas glass microfibers have to be heated to high levels and carefully sculpted at great expense. Huby's silk is collected by a group of molecular spectroscopy experts led by Michel Pézolet of Université Laval in Quebec, then integrated into circuits at her team's lab at Rennes. To her knowledge, this is the first time the optical properties of pristine silk have been exploited.
By integrating real spider silk into a microchip, the researchers found that silk could not only propagate light but could also direct light, or "couple" it, to selected parts of the chip. Huby hopes this work can be used to create biosensors that could detect the presence of a molecule or the activity of a protein: as light waves passed through a blood sample, for example, the molecules would change the properties of the light wave in an observable way.

Source:http://www.osa.org/en-us/about_osa/newsroom/newsreleases/2012/eco-friendly_optics_spider_silks_hidden/

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University of Washington researchers focus on quorum sensing to better understand bacteria

The relatively new field in microbiology that focuses on quorum sensing has been making strides in understanding how bacteria communicate and cooperate. Quorum sensing describes the bacterial communication between cells that allows them to recognize and react to the size of their surrounding cell population. While a cell's output of extracellular products, or "public goods," is dependent on the size of its surrounding population, scientists have discovered that quorum sensing, a type of bacterial communication, controls when cells release these public goods into their environments.
In a study appearing in the Oct. 12 issue of the journal Science, University of Washington researchers examine the pathogen Pseudomonas aeruginosa, which colonizes in the lungs of cystic fibrosis patients. While most cells "cooperate" with each other by producing and sharing public goods when there are enough of their "friends" around, researchers have found that certain individual cells, known as "cheater cells," share in the use of these extracellular products without releasing any of these products themselves.
In Pseudomonas aeruginosa these cheaters are quorum sensing mutants that don't make public goods in response to increasing population density. When the researchers manipulated the environment so that the cost of cell cooperation was high (so that the bacterial group had to produce a lot of public goods to survive), the cheater cells overtook the cooperating producer cells, the cooperators then became too rare, and the population collapsed. From this sequence of events, the researchers induced destabilization of cooperation. They also manipulated environmental conditions to restrict cheaters and stabilize cooperation. Scientists recognize this fundamental research as taking them steps closer to a different antibiotic-independent way to manage infections.
"Perhaps, one day, we'll be able to manipulate infections so that bacterial cooperation is destabilized and infections are resolved, "said Dr. Peter Greenberg, UW professor of microbiology and one of the three authors of the study.
"Biologists think of social interactions as being the push and pull between cooperation and conflict," he explained. "This is true of man and bacteria. Not so many years ago, people didn't think bacteria socialized at all. Now we are beginning to think we might manipulate bacterial social activity for the benefit of human health."
In the future, Greenberg said, this research may enable scientists to manipulate bacterial conditions in order to cause cell populations of dangerous pathogens to collapse.
"By learning about the fundamentals of quorum sensing control of cell cooperation, we are beginning to have a glimmer of insight into how to control and manipulate infecting populations of P. aeruginosa and other dangerous pathogens with similar systems," Greenberg said. "We've also gained new insights into how cell cooperation can be stably maintained in biology. It is much more straightforward to study sociality in bacteria than in animals. The payoffs may be in understanding what drives cooperation and conflict in general, and in developing strategies for infection control. "

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DAAD Research Internships in Science and Engineering (RISE)

Researchers engaged in the fields of Science and Engineering can receive assistance in their research projects from German interns having academic training in the fields of biology, chemistry, physics, earth science, engineering, or a closely related field

Target Group
In India: Research groups, professors, postdoctoral and PhD students employed by or affiliated with an accredited academic institution or a non-profit research institution in India.

Duration
6 weeks up to 3 months; between June and October 2013

 Requirements and Conditions
Researchers, research groups, professors, PhD and postdoctoral students to ensure scientific and academic supervision of the as-signed German intern. In addition, to provide support in local administrative matters, finding accommodation and if possible, suggesting recreational activities.

Application Procedure
The application submission process is online. Kindly visit the web-site www.daad.de/rise-programs where Indian participants can submit their project proposal (including a one to three-page project description) in the database which opens on October 08, 2012. The deadline to enter the project offer is November 25, 2012

for further information visit :http://www.daad.de/rise-programs/en/index.html

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DAAD :Working Internships in Science and Engineering (WISE)

Golden opportunity for a 2-3 months internship at institutions of higher education and research institutes in Germany with German doctoral students, scientists or professors as part of on-going research projects

Target group
Students pursuing Bachelor degree/ Dual degree/ Integrated programmes in subjects like engineering, mathematics, natural sciences etc.from selected Indian Universities (list of institutions )

Duration
 Duration of 2 up to 3 months, but not exceeding 90 days Scholarship

Value

• A monthly financial assistance of Euro 650 * contributing to subsidies living expenses.
• A lump sum travel subsidy of Euro 550.
• Compulsory health insurance covered by DAAD. 

Requirements and Conditions

• Indian students:

                    pursuing full time Bachelor degree programme at one of the

                    selected Indian Universities (see list attached) who are enrolled
                    in their 5th and 6th semester at the time of application.

                                                         or
                     pursuing full time Dual Degree/ Integrated programme at

                     one of the selected Indian Universities (see list attached)
                     who are enrolled in their 5th, 6th, 7th and 8th semester at the
                     time of application.

• Aggregate marks of 85% and above or CGPA 8.5/10 and above of completed semesters at the time of application.
• The applicant must be a registered student of his/her institution.
• Acceptance cum invitation letter from a German Professor for the internship. Only one invitation letter will be accepted.
• Private research institutes and private companies cannot be considered under this programme as a German host institution.
• German language skills are not mandatory.
• Candidate must be a resident of India and an Indian national.
• Applicant must have a valid Passport at the time of application.

Application procedure
The application submission process is online. The link is available on the DAAD New Delhi website.
The deadline for submission of applications is 01st of November.
Important:

 

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Khorana Program for Scholars

University of Wisconsin-Madison (UW), the Department of Biotechnology (DBT), Govt. of India and Indo-US Science and Technology Forum (IUSSTF) are partnering to support the prestigious Khorana Program for Scholars named in honor of Dr. Har Gobind Khorana, who won the Noble Prize in 1968 for his work at the interface of Chemistry and Biology while a member of the UW faculty. The Khorana Program will provide opportunities to Indian students to undertake research at University of Wisconsin-Madison (UW) and partner universities in Summer 2013 for a period of 10 weeks.


The Khorana Program is envisaged to

• Provide encouragement to young scholars to undertake R&D
• Enable students to carry out research at a premier University in the United States
• Transform research into societal benefits
• Build a seamless scientific community between India and the United States

B.Tech, M.Tech and M.Sc. students currently enrolled in recognized institutions of higher education in India in the areas of Biotechnology (including agricultural, health and biomedical sciences) are eligible to apply.

Scholarship includes: Stipend, Accommodations, Airfare

Program dates: May – July 2013

Application deadline: 30 November 2012
for further information visit : http://indousstf.org/Khorana/khorana_program.html

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