Lab Product News January 2014

FIGHTING FOR SCIENCE IN CANADA 8 >>>

IMAGING THE WORLD’S BRIGHTEST PROTEIN 16

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PREDICTIVE TOOLS SPUR INNOVATION 20

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JANUARY 2014

labcanada.com Photo credit: Kevin O’Donnell

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RAISING THE BAR ON CHEMICAL SAFETY 14

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Industry News

TORONTO BRAIN RESEARCHER WINS NEW AWARD Sunnybrook neurosurgeon Dr. Leodante da Costa has received $300,000 funding to advance his brain injury research, as one of 16 winners in the first round of GE and the National Football League’s Head Health Challenge.

Launched in 2013, the challenge aims to enhance the understanding of traumatic brain injury and advance technology solutions to better diagnose and treat such conditions.

Dr. da Costa’s research was selected among 400 entries from 27 countries.

His research focuses on ways to detect and measure the ability of the blood vessels in the brain to respond in the event of head injury. The research was highlighted as an area of interest by the challenge’s panel of leading healthcare experts and advocates in brain research and imaging technologies.

“We are most pleased to receive this funding that will help us to extend our work in improving imSee Dr. da Costa DISCUSS THE AWARD aging diagnosis of patients with traumatic brain injury,” he said.

GE and the NFL will also support Dr. da Costa’s research through ongoing mentorship and access to GE’s researchers, facilities and industry expertise.

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Industry News

NEW APPROACH TO TREATING COLORECTAL CANCER

DR. JOHN DICK. IMAGE COURTESY OF UHN Photographics

Researchers at Princess Margaret Cancer Centre have discovered a new approach to treating colorectal cancer by disarming the gene that drives self-renewal in stem cells that are the root cause of disease, resistance to treatment and relapse.

“This is the first step toward clinically applying the principles of cancer stem cell biology to control cancer growth and advance the development of durable cures,” says principal investigator Dr. John Dick about the findings published online recently in Nature Medicine.

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In pre-clinical experiments, the research team replicated human colon cancer in mice to determine if specifically targeting the stem cells was clinically relevant. First, the researchers identified that the gene BMI-1, already implicated in maintaining stem cells in other cancers, is the pivotal regulator of colon cancer stem cells and drives the cycle of self-renewal, proliferation and cell survival. Next, the team used an existing small-molecule inhibitor to successfully block BMI-1, thus demonstrating the clinical relevance of this approach. “Inhibiting a recognized regulator of self-renewal is an effective approach to control tumour growth, providing strong evidence for the clinical relevance of self-renewal as a biological process for therapeutic targeting,� wrote Dr. Antonija Kreso, lead author.

Watch Dr Dick discuss the finding on a VIDEO

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SCAVENGER HUNT FOR RESEARCH The hunt is on in a Virtual Scavenger Hunt launched by Ontario’s universities. It takes the public on a fun online journey through the world of research at the province’s universities.

The month-long contest, which began on February 3, is open to students and the general public. The Council of Ontario Universities, which is organizing the effort, says contestants can solve new clues every day to enter for prizes. Intrepid scavengers who get all 21 clues correct will be able to unlock a secret message which they can submit to be entered for grand prizes.

Students from each of the participating universities will deliver daily video clues via email to registered contestants whose answers can be hunted down online. Clues will also be available on the Research Matters website.

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Product Videos

Controllers enable quick changes to experiments MCD-Series bidirectional mass flow and pressure controllers control mass flow rate, volumetric flow rate and absolute pressure of gases in two flow directions. Flexible dualvalve design allows researchers to replace multiple dedicated instruments and make rapid changes to experimental setups.

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Video introduces CHN microanalysis technique CHN microanalysis is a powerful and relatively straightforward method for determining whether or not a sample is pure by providing a precise and accurate analysis of its percentage carbon, hydrogen and nitrogen content. Video introduces CHN microanalysis using the Model 440 CHN microanalysis system.

Horizontal furnace enables it to deliver precise and accurate results without constant system optimization.

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Pipette increases throughput for high-volume experiments

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Fast, convenient real-time PCR setup A new customer testimonial video demonstrates how the Viaflo Voyager motorized adjustable spacing pipette can be used to rapidly set up a 384-well qRT-PCR plate for analysis in a ViiA 7 Real-Time PCR system (Life Technologies). The researcher shows how it is routinely possible to pipette 64 samples in triplicate for two genes of interest in under 10 minutes.

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System images 3D blocks of structures Researchers can image 3D structures of biological and materials samples at ultrahigh resolution using JEOL’s JSM-7100F field emission scanning electron microscope with an integrated Gatan 3View serial block face imaging system. The automated sectioning and image capture system is designed for FE SEM, and turns an embedded sample into thousands of images overnight or tens of thousands over a few days.

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FIGHTING for SCIENCE Many scientists in Canada fear that changes being made to our nation’s science policy are detrimental to the future of science in this country.

The Canadian Association of University Teachers has launched a campaign to promote awareness about this issue, and its executive director, James L. Turk, recently spoke to Lab Product News about the issues facing Canadian scientists today.

BY REBECCA REID, LAB PRODUCT NEWS

T

he past year-and-a-half has seen unprecedented protests by scientists across Canada.

Concerns have been growing about the way the federal government is refusing to let its government scientists speak freely about their research, how it is channeling funding away from basic research and toward applied research, and turning our research institutes into arms of industry, among other issues.

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Protesters send a message to the federal government at the Ottawa rally. Photo credit: Kevin O’Donnell.

Starting with the ‘Death of Evidence’ rally in Ottawa in July 2012, scientists and other citizens have taken to the streets to express their concerns about the state of science in the country. Protests have also been held to oppose the planned closures of the Experimental Lakes Area in Northern Ontario and the Kluane Lake Research Station in the Yukon.

And last September, scientists again obliged — this time in the thousands in cities across the country — when the advocacy group

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Evidence for Democracy asked them to organize local demonstrations to voice their concerns about the state of science in Canada. Across the country, the effort was one of the largest nationwide pro-science rallies in Canadian history.

Along with their colleagues in government and the private sector, the Canadian Association of University Teachers (CAUT)’s members believe the government’s policy changes are doing great harm to science in Canada.

And despite increasing and persistent criticism, Stephen Harper’s Conservative government has so far resisted rectifying its policies that have unarguably changed who gets to conduct scientific research in Canada and how that research is done.

CAUT — a federation of faculty associations of 124 colleges and universities across the country, which represents about 68,000 university and college teachers — is raising awareness of these issues through an

Town hall meeting recently held in Vancouver.

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ongoing, nationwide series of town hall meetings dubbed “Get Science Right”.

“The challenge of putting together the campaign is there are a number of problems with how the federal government is approaching science and research,” says James L. Turk, CAUT’s executive director.“The campaign is an attempt to highlight those different ones — some of which have received reasonable public attention, some haven’t — [and] to build public support for some funda- Evidence for Democracy rally in Ottawa in September 2013. Photo credit: Kevin mental changes in how the federal O’Donnell. government deals with science and research.”

The muzzling of federal scientists is the issue that has received the most attention thus far, he notes.

The issue came into alarming focus in 2011, he says, when Kristi MillerSaunders, a scientist at the Department of Fisheries and Oceans, and head of the federal Pacific Biological Station on Vancouver Island, reported to the media that she was prevented by the Privy Council Office from speaking about the results of her investigation into the dwindling salmon stocks in B.C.

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Her research revealed a virus may be the culprit responsible for the deaths of Pacific Salmon before they reach their spawning grounds.

Articles appeared in numerous publications including a July 27, 2011 piece published by Postmedia entitled “Ottawa silences The future of science and research in Canada scientists over west coast is in jeopardy. Join the campaign for a science policy that puts the public interest first and salmon study”. builds upon the proven strengths of academic The writer, Margaret Munro, and government research. revealed in her article that GetScienceRight.ca documents obtained through the Access to Information Act show the Privy Council Of#getscienceright fice quashed a media release about Miller’s findings and wouldn’t allow her to do interviews, despite numerous requests from media, and that the results of her study had already been published in the well-respected Science magazine.

And, the government has devised new guidelines that require a lengthy approval process before a scientist can speak with the media.

GET SCIENCE R!GHT PI-LENS/SHUTTERSTOCK.COM

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The Environmental Law Clinic at the University of Victoria released a lengthy report, Muzzling Civil Servants: A Threat to Democracy, in early 2013, that included policy statements and emails acquired through the Access to Information Act demonstrating how the government is preventing the media from speaking with government scientists.

The report revealed the government is purposely preventing its scientists from speaking directly and freely to the media, and purposely attempts to discourage media interest by taking weeks to approve requests for interviews. By the time the request for an interview has been granted, the news outlet has often moved onto another topic.

The effect has been less media coverage of hot-button issues like climate change, as well as fewer requests for interviews.

When an interview is granted and a scientist is able to speak to the media, the report revealed they’re often not allowed to speak freely. Instead, they have to respond along approved media lines written by communications officials.

Politically inconvenient results In many cases, scientists are forbidden to speak when their results are not supportive — or could undermine — a policy decision made by the government. Turk describes these types of results as “politically inconvenient.”

The union to which most federal scientists belong, the Professional Institute of the Public Service of Canada, has taken an interest in the matter and commissioned Environics Research to survey 15,398 federal scientists across 40 government departments and agencies — 4,069 responded.

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The findings were published in a report dubbed The Big Chill: Silencing Public Interest Science, A Survey, which was released on October 21. Some of the key findings included: •9 0% said they did not feel they could speak freely to the media about their work; •8 6% said they feared retaliation or censure if they spoke to the media or public about a decision made by their department or agency that could harm public health, safety or the environment; •5 0% reported being aware of cases where political interference compromised health and safety of Canadians or the environmental sustainability; •3 7% were prevented from responding to questions by the public and media by public relations staff or management over the past five years; and •2 4% had been directly asked to exclude information from reports for nonscientific reasons.

But government scientists aren’t the only ones being censored.

Extending the veil of silence “Earlier this year it became clear they were extending it beyond government scientists to muzzle academic scientists who are working with government scientists,” says Turk.

This came to light when University of Delaware physical oceanographer, Andreas Muenchow, went public about a research agreement he received from the Canadian government that asked him to sign away his rights to publish his findings without express written consent of the federal government.

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Articles appeared in media outlets such as the CBC website: Canadian federal research deal potentially muzzles U.S. scientists.

Turk says agreements Scientists came out in the thousands like these could deter at rallies across Canada in September.

Photo credit: Kevin O’Donnell. scientists from around the world from collaborating with Canadian scientists in the employ of the federal government because they aren’t able to publish their findings freely.

Funding cuts Muzzling is just the tip of the iceberg, although it has received the most attention, says Turk.

Sweeping modifications to granting procedures, favouring applied, industryfocused research over basic research, cancelling important research programs as well as the long-form census, have all combined to make Canada a difficult place to conduct basic research.

These changes have a huge impact on research in Canada because the principal source of funding for scholarly research is through the federal granting councils — the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation (CFI) and the Social Sciences and Hu>>> manities Research Council (SSHRC).

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“Those are the bodies that fund the overwhelming proportion of academic research,” says Turk.“And that’s important in Canada because there’s no country in the world that relies more on academic research and government science than Canada. The reason for that is because there’s so little genuine research done in the private Figure 1 sector in Canada.”

The Conference Board of Canada says Canada has been receiving ‘D’ grades for business enterprise R&D (BERD) spending since the 1980s, and ranks 15th out of 16 peer countries.

In the U.S., BERD spending as a percentage of GDP is Figure 2 double the amount spent in Canada, and in Finland – with a population of just 5.4 million – it is three times higher.

The CAUT reports that grant money provided by the granting councils has also been reduced. Figure 1 shows that between 2007 and 2012, overall base Visit us online www.labcanada.com INDEX

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funding decreased by 7.5%. This is at the same time the number of number of university-based researchers in Canada grew by 9.5% — from 38,313 in 2007-08 to 41,934 in 2010-11, according to an October 2013 report in CAUT’s Educational Review.

Now, not only is the amount of academic research funding being cut, but it’s being shifted away from basic research towards applied research.

Figure 2 provides an example of how applied research (that is,‘fettered’ to academic-industry partnerships) is getting a bigger share of the pie — in this case, fettered research now receives more NSERC funding than does basic research.

CAUT says all new funding approved for 2013 is being allocated towards research conducted in partnership with industry.

While application-focused research is important, cutting basic research will impact innovation in the future. As Turk explains,“You can’t apply science that hasn’t been developed.”

Many scientists don’t know how their basic research will be applied to develop new products and Turk adds that he has heard some say they feel as though they must invent potential applications just to get their funding renewed.

He said the change in funding reflects policy changes that are “being driven by political priorities not scientific policies,” and that it seems the federal government currently believes scientists “should be functionaries that do what they’re told” and that they should be “the arm of industry.”

A further example is the change that has been made to the country’s storied research organization, the National Research Council (NRC). In the past couple of years, its work has been gradually shifted away from basic >>> research and toward making it a ‘toolbox for industry’. Then, last May, January 2014 CHEMICALS

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the federal government made the announcement that the NRC had been “transformed into an industry-focused research and technology organization.” And,“the refocused NRC will work with Canadian industries to bridge technology gaps, helping build a more innovative Canadian economy.”

NRC now has a special Web portal, promoting its new role as a “Concierge Service” for industry.

Fighting back and moving forward To prevent politics from interfering with science, CAUT would like the research councils to become arms-length organizations that function with little government interference.

Turk said his organization is also calling for the re-creation of a parliamentary science officer — a position axed by the Harper government — who can provide impartial advice on scientific matters.

On Parliament Hill, the NDP also wants to make this happen. Science and Technology Critic, Kennedy Stewart, announced in late November that he was tabling a new bill to create an independent Parliamentary Science Officer.

The bill received first reading in the House of Commons in early December.

“After years of muzzling, mismanagement and misuse of science by the Conservative government, this new office will promote real transparency and ensure decisions made in Ottawa are based on the best available scientific evidence,” he said in a statement.

The Get Science Right campaign has already made several stops across the country, most recently in Vancouver, and the Town Halls will continue for another year.

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page 13

“This is a long-term initiative,” Turk explains.“Scientific work is so important to the future of Canada, and our misguided science policy is so harmful, and we’ve done everything we can to have discussions with the government about [how] we see it moving in an incredibly wrong direction and we’ve had very little success.”

Even though some scientists are concerned that speaking out could cost them their research grants, Turk says they haven’t had any difficulty finding people for their panel discussions.

During the events, panelists discuss challenges facing scientists in Canada today and invite public participation.

“It’s our sense that we have to make this a discussion with the public. It’s not sufficient simply to have researchers, and scientists — whether they’re in universities, the private sector or government — talking among themselves and wringing their hands. If there’s going to be a change, we have to have a discussion about what it means for them and what it means for Canada,” he says.

Other organizations are also working to change the policies implemented by the Harper government.

Following its successful rallies across the country, for example, Evidence for Democracy is now running an online letter-writing campaign called Science Uncensored to ask the leaders of all five federal parties to claw back the policies that are preventing scientists from openly speaking to the public.

So far it has gained over 7,000 signatures.

All in all, Canadian scientists are facing a tough battle, and thankfully there are still many willing to put up a fight. LPN January 2014 CHEMICALS

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Chemicals

RAISING THE BAR ON CHEMICAL SAFETY

Helsinki Chemicals Forum 2013.

Photo credit: Kimmo Brandt

Chemical safety is a multi-faceted, hot-button issue, and each year the organizers of the Helsinki Chemicals Forum take aim at some of the most challenging problems facing the global chemical industry. Their ultimate goal is to improve the level of discussion and ultimately help to raise the bar on chemical safety standards.

BY LESLIE BURT, LAB PRODUCT NEWS

C

lose to a decade ago, the European Union took the lead internationally when it passed regulations requiring the registration of all chemicals produced and in use within its borders. In addition, the regulations also require the classification and ultimate substitution of hazardous chemicals.The Visit us online www.labcanada.com INDEX

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page 14

regulations, called REACH, have been in force since 2007. Phased in gradually over a number of years, the regulations are already considered to be a success.Thousands of substances have been registered, and medium volume chemicals are now being evaluated by authorities, and substitutions of some hazardous substances have already begun.

But the chemical industry is global, and beyond the EU, a key objective is to help promote the enactment of similar legislation in other countries, along with ensuring harmonization of standards internationally.

The Helsinki Chemical Forum (HCF) was founded in 2009 to support this goal, along with the examination of issues regarding chemicals management and the promotion of global chemical safety. Each year, its organizers bring together international authorities, industry leaders, NGOs, academics and other interested parties to share in an open dialogue about these topics.

Last June, HCF 2013 probed important issues such as the regulation of nanomaterials, the shortcomings of current chemical data safety sheets in covering the complex mixture of chemicals used in manufacturing, and goals for sound international management of chemicals.

In the debate devoted to nanomaterials, panelists discussed definitions of nanomaterials and whether they are currently already covered by REACH. In addition they highlighted the need for developing standards for appropriate testing methods that can be applied internationally.

A panel that probed the sound international management of chemicals and goals set for 2020 was led by Environment Canada’s Jake Sandersson.The 2020 goal was established in 2002 by the Johannesburg Plan of Imple- >>> January 2014 CHEMICALS

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Chemicals

mentation of the World Summit on Sustainable Development, and aims to achieve “the sound management of chemicals throughout their life cycle and of hazardous wastes for sustainable development as well as for the protection of human health and the environment.�

Following this declaration, in 2006 the Strategic Approach to International Chemicals Management (SAICM) was established with the objective of ensuring that by the 2020 target date, chemicals are produced and used in ways that minimize significant adverse impacts on human health and the environment.

Panel members debated how these goals might be achieved. While OECD is active in trying to share tools and information among members, these tools actually need to be used. At the same time, panelists agreed that more binding agreements are needed, and harmonization between regulations.

This year, HCF will continue the dialogue on these topics of vital interest, with this year’s programme recently finalized. Delegates will hear about the ongoing free trade negotiations between Europe and the US and problems originating from differences in chemicals regulations. Panelists will take a look at fracking and debate whether the political controversy is scientifically justified.The many contradicting scientific studies of endocrine disruptors will be examined, along with views about the need for special controls on these chemicals. Panelists will also take a look at recent developments in chemicals management around the world to see just how close or far away the goal of international harmonization of chemical regulations really is. At the same time, they will look at what is needed to assist rapidly growing and developing economies, and what paths they can choose to promote sound chemical management programmes.

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“We have a very impressive representation of leading authorities, NGOs and key industries in most panels,” says Hannu Vornamo, secretary general of HCF. “This gives us the chance to achieve something new. If we take a more global approach, the big problem in chemicals safety is the poor baseline in too many countries, rather than poor control in industrialized countries. Global harmonization on regulation will not proceed unless we can encourage new developments in growing economies and developing countries on this field.”

For the first time this year, each day will include workshop sessions aimed at allowing participants to engage more and transform the forum into a thinktank. Joining the workshop participants and drawing input from the panel discussions and message walls, professional facilitators will produce remarks and conclusions about each topic.

“Our target is really to promote chemicals safety globally and to improve the level of discussions around chemicals, which so often suffer from lack of facts and poor communication,” says Vornamo.“[In] other words, our intention is to achieve for HCF a stronger role as one of the leading discussion forums on global chemicals safety and management issues.” LPN

See highlights of HCF 2013 in short VIDEO

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Microscopy

IMAGING THE WORLD’S BRIGHTEST PROTEIN

O

ptogenetics is revolutionizing the field of behavioral neuroscience by enabling researchers to control the activity of individual neurons and measure the effects of those manipulations. Introduced in 2006, it was selected as Nature Methods’“Method of the Year” only four years later.Today, hundreds of labs are using the technique to explore the neurobiology of phenomena such as decision-making and neurodegenerative diseases, often with remarkable results. For example, researchers have demonstrated how light can steady the gait of a stumbling rat with Parkinson’s disease.

Fluorescent imaging is a widely used technique to gain insight into biological functions. But problems can arise when external illumination is required, as in optogenetics:The same light that stimulates what’s under optogenetic control can interfere with the fluorescent sensor. For instance, the same blue light that excites the FRET-based indicator for calcium activates a commonly used photo-sensitive receptor used in optogenetics.

Light can be generated instead by chemiluminescence – where the emission is produced by a chemical reaction – but existing chemiluminescent probes are too weak for use in optogenetics studies. A means to create brighter chemiluminescence would help to advance these and other applications.

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page 16

The challenge Takeharu Nagai, PhD, Department of Biomolecular Energetics, Institute of Scientific and Industrial Research at Osaka University, and inventor of a number of ingenious fluorescent and chemiluminescent probes, decided to take up the challenge of developing a probe compatible with optogenetics studies – in large part, he said, because he had questions of his own he wanted to answer.

“To investigate the input-output relation in living cells, compatible use of optogenetics and fluorescent indicators such as calcium ion (Ca2+) are very useful combinations,” said Dr. Nagai.“However, because fluorescent indicators require excitation light source, such excitation light gives perturbations to the cell function as photo-stimulation light.”

The solution To overcome this problem, Dr. Nagai’s lab engineered a probe that fuses a luminescent protein from the sea pansy Renilla reniformis with a fluorescent protein they previously designed.The new molecular entity – dubbed Nanolantern – is the world’s brightest luminescent protein, with temporal and spatial resolution equivalent to those of fluorescence.

According to Dr. Nagai, dispensing with the need for light illumination, which is essential for fluorescence imaging,“allows us to analyze dynamics in environments where the use of fluorescent indicators is not feasible.”

The results Having designed the new, considerably improved protein – it is ten times

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Microscopy

brighter than the original template (RLuc) – Dr. Nagai’s team decided to put it through its paces. First, they used it to image intracellular structures in living cells, demonstrating spatial resolution and brightness on par with those of fluorescence. Collaborating with Dr. Yuriko Higuchi at Kyoto University, they visualized cancer tissue inside a freely moving mouse. Here, the Nano-lantern offered a number of advantages over conventional probes, including increased sensitivity and shorter exposure times. It even enFigure 1 abled video-rate imaging of tumours 17 Luminescence (left) and fluorescence (right) imaging of HeLa days after implantation. cells expressing Nano-lantern Next, Dr. Nagai’s group modified the targeted to cytoplasm, mitochondria and histone H2B. The exposure Nano-lantern into a calcium sensor and times for the luminescence images co-expressed it with a light-sensitive phowere 3 s, 3 s and 1 s, respectively.

The exposure time for all fluorestoreceptor in rat neurons. Fluorescent cence images was 1 s. The reference fluorescence signal was Ca2+ indicators by themselves would be captured by exciting Venus with light at 490 nm. Scale bars, 50 mm. triggered by light, making it impossible to perform optogenetics.This co-expression system allowed the researchers to follow excitation of the photoreceptors by measuring the Ca2+ increase as reported by the Nano-lantern Ca2+ indicator.

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They were also able to visualize ATP production in plant chloroplasts.

They converted the Nano-lantern into an ATP sensor, and expressed it in a live leaf.The red autofluorescence signal of the chloroplasts did not interfere with the Figure 2-3 Nano-lantern, allowing Representative luminescence images of the indicatobservation of the ined numbers of injected cells at 600 s (2) and 1 s exposures (3). crease in ATP levels after light irradiation – as well as the first visualization of the qE quenching-mediated down regulation of ATP synthesis in live plant cells.

To visualize Nano-lantern signals, Dr. Nagai and his colleagues used a Photometrics’ Evolve 512 EMCCD camera.

“We knew that the Photometrics’ cameras worked very well because we used Photometrics Cascade II EMCCD before the Evolve,” said Dr. Nagai who has been using Photometrics cameras for more than a decade.

The Evolve’s high quantum efficiency allowed Dr. Nagai’s lab to easily detect the low chemiluminescent signals of RLuc for both still images and video-rate imaging without the risk of phototoxicity.The camera’s cooling >>> (-85ºC) increased the signal-to-noise ratio for the mouse tumour imagJanuary 2014 CHEMICALS

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Microscopy

Figure 4 Consecutive frames of video-rate images of Nano-lantern- expressing tumour cells in an unshaved mouse. The luminescent signal every 60 ms is shown in green in the still images and as a series of pseudo colours (blue, cyan, green, yellow, red and magenta) in the merged image. Scale bars, 1 cm.

ing, while its wide dynamic range enabled acquisition of both chemiluminescent and bright-field images using the same camera setting.

The Evolve 512 EMCCD also offers a feature that allowed Dr. Nagai’s team to perform “cleaner” optogenetic experiments. Because the light used to stimulate optogenetic processes is so strong, it can increase the background noise level.To overcome this issue, Dr. Nagai and his colleagues used the dead-time of the Evolve 512 camera to conduct optogenetic light stimulation.This feature is not available with other cameras.

“One of the unique advantages of Evolve 512 is that it can erase charges on the CCD during the dead-time,” said Dr. Nagai.“This function contributed to reduced background noise for compatible use of optogenetic and chemiluminescent imaging.”

“Now, all biological phenomena that are regulated by light, including photosynthesis and photoreception in retina, can be viewed using Nano-lantern, giving us more dynamic and quantitative analysis of living cells,” he explained.

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Looking forward Dr. Nagai is already hard at work creating new colours for the Nano-lantern and boosting its brightness, which could lead to single-molecule-level imaging.

As there are no plans to commercialize the Nano-lantern, he’s making the DNA construct freely available.

Dr. Nagai expects that the increased brightness of Nano-lantern will make possible more advanced applications such as high-throughput drug screening and single-cell tracking in live animals and plants.

“Nano-lantern can help realize the other advantages of low-intensity light imaging, including diminished photobleaching and phototoxicity, which allow for prolonged observation without harming the cellular substrate,” he said.

Dr. Nagai notes that rapid consumption of the luminescent substrate by Nano-lantern hampers prolonged observation of biological events, especially in the case of whole-body imaging.To address this issue, he and his team are working to develop a method that facilitates indefinite observation applicable to the entire organism. LPN Related articles 1. K Saito,Y Arai,T Nagai et al. Luminescent proteins for high-speed single-cell and whole-body imaging. Nature Communications. 2012; 3:1262. (December 11, 2012).

2. YF Chang,Y Arai and T Nagai et al. Optogenetic activation during detector ‘dead time’ enables compatible real-time fluorescence imaging. Neuroscience Research. 2012; 73:341–347.(August, 2012) Related videos: 1. Nano‐lantern‐expressing tumor cells in the unshaved freely moving mouse: www.photometrics. com/resources/videos/nagai.nano 2. Pseudo coloured ratio images of a rat hippocampal neuron expressing Nano‐lantern (Ca2+) recorded at 10Hz : www.photometrics.com/resources/videos/nagai.ratio January 2014 CHEMICALS

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NEW TECHNOLOGY MAKES ASSAYS FASTER New assay technology is faster, easier for epigenetic research

A

cademic groups and biopharmaceutical organizations involved with epigenetic research are reporting positive feedback for the Chromatrap chromatin immunoprecipitation (ChIP) assay technology.

The researchers say they are finding the ChIP assays to be faster and easier to use than conventional bead-based assays. The assay technology was developed by Porvair Sciences in conjunction with the Department of Life Sciences at the UK’s University of Swansea and uses a solid-phase porous polymer functionalized with protein A, which the company says allows the chromatin capture to be more efficient than bead-based methods.

“What I like most about the Chromatrap kit compared to traditional beadbased ChIP assays is the ease of use, speed and reliability,” said Brian J. Engel, a biochemistry & cell biology researcher at Rice University.“There is no worry about accidentally losing beads during washes and reducing output chromatin when using the column-based method.”

“We have found that the Chromatrap kit is quick, reliable and flexible,” said Curt Warren, Engel’s colleague.“Saving reagents and time with this kit makes it easier and more feasible to conduct more thorough and effective IP based experiments. With the enhanced reproducibility using Chro>>> matrap, I would not go back to bead-based ChIP and the assay has January 2014 CHEMICALS

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been fully endorsed and adopted within our research team.”

“Chromatrap streamlines the complicated experimental procedure associated with chromatin-IP making it a much quicker and user-friendly assay compared to conventional bead-based assays,” says Professor Steve Conlan, head of molecular & cell biology at Swansea University.“Using this kit we obtain much more consistent data, and most importantly can use much less input sample. We have made a permanent switch to using Chromatrap for all our cell line and primary cell based assays, and fully endorse the technology.”

“What I like about the Chromatrap assay is the ease of use and quick method allowing me to analyze my data in the same day,” said Dr Helen Whiteland, Professor Conlan’s research assistant.

“An expanding number of proven application solutions and the introduction of the Chromatrap 96 HT solid-state ChIP high throughput platform has enabled us to more than double the number of research groups using ChromaTrap assay technology during the last 12 months,” said Stephen Knight, Porvair’s sales and marketing director.“We are particularly pleased by the very positive feedback from early adopters of the technology.” LPN

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PREDICTIVE TOOLS SPUR INNOVATION

BY ADRIAN STEVENS, PH.D., SENIOR MANAGER OF PREDICTIVE SCIENCES MARKETING AND LIFE SCIENCES, ACCELRYS, INC.

O

n Oct. 9, 2013, the Royal Swedish Academy of Sciences announced the winners of the 2013 Nobel Prize in Chemistry. In an outcome guaranteed to capture the attention of chemistry and biochemistry researchers around the world, the award was given to Professors Martin Karplus of Harvard, Michael Levitt of Stanford and Arieh Warshel of USC “for the development of multiscale models for complex chemical systems.” The award recognized their work in bringing together the classical Newtonian molecular mechanics methods with the methods of quantum mechanics, enabling scientists to model large complex chemical systems and reactions.

This Nobel announcement was, of course, welcome news to Professors Karplus, Levitt and Warshel and an overdue recognition of their contributions to the field of molecular simulations. Arguably, it can also be seen as a broad recognition of the value that predictive sciences can now offer to aid our understanding of how molecules interact in chemistry and biology.

The predictive multiscale models and methods developed by Karplus, Levitt, Warshel and others have fundamentally changed the way scientists innovate in bringing new drugs to market.1

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Remembering the way things were Over the past 30 or so years, mathematical models of molecular systems have evolved from purely theoretical tools into robust, reliable and broadly accurate Solvent exposed surface on the fAb domain of an antibody, colored to show the predicted binding site ‘hot-spot’ (red) as predictive tools. Procalculated by the spatial aggregation propensity algorithm, Aggmap. Such structure models can be built to high precipelled by the steady sion now with a combination of knowledge-based homolimprovement in compuogy modelling (Modeler) and structure preparation and refinement (CHARMM). tational performance championed by this year’s three Nobel winners and their colleagues around the world, many of these tools are now directly integrated into the standard toolkit used by research scientists today. Indeed, many readers of this article might note that such tools are now even starting to make an appearance on their smart phones! The tools have evolved from the limited preserve of very few specialists to use by a much broader population of scientists.

To demonstrate the democratization of predictive sciences over the years, I cast my mind back to the heady days when computational chemists ran programs like Quanta™ on massive old (and usually very hot) Silicon Graphics computing platforms. These were typically massive and pricy machines, and were often hidden away in broom closets, far removed from the Visit us online www.labcanada.com INDEX

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“real chemists”. In contrast, today, if you walk around any lab, you will now see computational and experimental researchers working together on new generations of the same tools, perhaps calculating the properties of a macromolecule or looking at how their next compound idea is predicted to bind to a protein target. Today, we consume science directly; it is no longer segregated from the discovery process.

New frontiers in rational biologics design One of the fastest growing areas of research today is the development of novel biologic therapeutics based on second- and third-generation antibody technologies. These antibodies utilize various engineering and optimization technologies to derive improved clinical properties including enhanced antigen binding, effector function, clinical safety and more. Bolstered by increasing drug approvals from the FDA in recent years2, combined with improved patent protection rights3, biotherapeutics have become one of modern medicine’s most valuable tools for treating and preventing illness. Some analyst forecasts are now projecting that biotherapeutics will comprise 50 percent of the top 100 drugs by 2018.4 With such promise and competition in biotherapeutics, efficient development is increasingly important. However, biotherapeutics development presents a number of unique challenges. Unlike small molecule drugs, storage and administration of biotherapeutics typically require the use of high-concentration solutions necessitating specific biophysical profiles including solubility, thermal and chemical stability and low aggrega-

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tion propensity. Testing for many of these properties and characteristics is typically time-consuming and expensive. It is also dependent on both experimental methods to test and on cell lines to express the biologic material, creating a major bottleneck for the industry.

To break the logjam and accelerate the development of promising biotherapeutics, the pharmaceutical industry is increasingly applying predictive methods to help identify and optimize the best biologic leads early. When applied in conjunction with experimental procedures, predictive methods can help researchers prioritize the selection of biologics. They can also identify potential undesirable properties long before any material has been expressed.

The multiscale modelling celebrated by this year’s Nobel committee highlights the increasing value of predictive sciences as an important tool supplementing experimental techniques. Much like the work of this year’s Chemistry laureates, these two complementary approaches to drug development have “opened up a fruitful cooperation between theory and experiment that has made many otherwise unsolvable problems solvable.”5 LPN NOTES: 1. For example, many pharmaceutical modeling tools are based on CHARMM (chemistry at Harvard macromolecular mechanics) — a molecular dynamics simulation and analysis program that was first developed by Karplus’ group decades ago. Accelrys Discovery Studio contains the only available commercial version of this widely used program.

2. EvaluatePharma: World Preview 2018 ‘Embracing the Patent Cliff”, EvaluatePharma, 2012.

3. ‘Patient Protection and Affordable Care Act (PPACA)’, Public Law 111 148, 124 STAT. 119, 111th Congress, 2010.

4. Ibid. 1 5. “Scientific Background on the Nobel Prize in Chemistry 2013: DEVELOPMENT OF MULTISCALE MODELS FOR COMPLEX CHEMICAL SYSTEMS,” The Royal Swedish Academy of Sciences, 9 October 2013, pg. 8.

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Instrument & Equipment News

Tailor your own UV viewing systems

The Spectroline CC-80 and CC-81 ultraviolet viewing systems are designed for use in chromatography, electrophoresis, genetic research, photoresist coating inspection and forensic science. Researchers can custom design their own fluorescence analysis systems by choosing from UV lamps available in 254, 312 and 365nm wavelengths.

Built-in white light sources provide visible illumination for easy sample prep.

Spectroline www.spectroline.com

Detector upgrades increase FT-IR/NIR sensitivity Extended detector options for the Spotlight 400 FT-IR/NIR imaging system enables more efficient sample analysis.

The new detector configurations support more sensitive high-performance NIR imaging for food, feeds and more, as well as longer wavelength MIR FT-IR imaging for inorganics, polymer and semiconductor applications. A new software module enables the simple creation of IR workflows for QA/QC, routine analytical labs and field measurement.

PerkinElmer www.perkinelmer.com/Catalog/Product/ID/L1860116 January 2014 CHEMICALS

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Convoluted tubing eliminates splicing

Flexible FEP convoluted tubing can turn corners and run through tight areas without kinking or collapsing and is still self-draining. Spring wire can be added if additional crush resistance is needed. It is also extremely clear and aids in visual inspection of the media flowing through the tube. Available in sizes .153� O.D. to 4� O.D.

Parker Hannifin www.texloc.com

Microscope extends the reach of 3D imaging X-ray microscopy (XRM) increases throughput for 3D imaging at the nanoscale by up to 10 times. The Zeiss Xradia 810 Ultra operates at 5.4 keV, a lower x-ray energy that delivers better contrast and image quality for many materials. Contrast improves significantly as these lower-energy x-rays are absorbed more strongly, enabling high-quality tomographies to be completed at vastly reduced imaging times.

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Automated pipetting systems suit many uses

Manual pipetting can be time consuming. Designed for effective automated liquid-handling applications, Eppendorf’s five new models of EpMotion 5075 systems combine accelerated operational speed, new software and hardware features, and an increased number of worktable positions, which makes them suitable for simple and flexible laboratory use across a wide range of liquid-handling applications.

Eppendorf www.eppendorfna.com

Peltier cooler reduces GC running costs

Designed for use with the Optic GC Inlet when conducting cold injections in gas chromatography, Peltier Cooler helps bring down the high cost of running inlet cooling by replacing the cryogenic system. The new unit uses dry compressed air or nitrogen gas as a cooling media, and it is especially suited to applications when cooling to subambient temperatures is not required.

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Instrument & Equipment News

New option for GC system conserves helium

Scientists using gas chromatography want to improve productivity without compromising performance. Thermo Fisher Scientific’s Trace 1300 Series GC system includes new options designed to conserve helium, permit use of multiple detectors simultaneously, automate sampling gas workflows and perform flame photometric detection. It can also be controlled by the Dionex Chromeleon chromatography data system to streamline the path from samples to results by simplifying workflows.

Thermo Fisher Scientific www.thermoscientific.com/trace1300

Super-res AFM system provides fast scanning A new atomic force microscopy (AFM) system is capable of delivering fast scanning and super-resolution on a single instrument platform, the NanoWizard Ultra Speed AFM. Users can track sample changes in real-time whether the sample is imaged in air or liquid.

Scanning at speeds of greater than 100 Hz line rate with true atomic resolution is enabled by the enhanced low noise of scanner, position sensor and detection system.

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Temperature, humidity data uploads to the cloud

With integrated Wi-Fi function, model TR-72wf temperature and humidity data logger automatically uploads recorded data to manufacturer’s free cloud-based WebStorage service. AP mode allows for direct log on and downloading of data by a smartphone or tablet.

Unit can be set up, configured and operated without using a PC. Temperature measurement range is 0 to 55°C with resolution of 0.1°C. TandD Corporation www.tandd.com

Polymer withstands repeated steam sterilization TPX polymethylpentene is a lightweight, transparent, semi-crystalline material with outstanding resistance to both steam sterilization and a wide range of chemicals. Items made with this polymer can be reused many times, promoting reuse rather than recycling. With a low density, the material also does not absorb water and transmits 92 to 94 percent of visible light, has a low refractive index and non-stick properties.

Goodfellow Cambridge www.goodfellow.com/larger-quantities/ polymers/tpx-products/

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Instrument & Equipment News

Bench-top NMR spectrometer safe for lab use

The Spinsolve Carbon now allows researchers to have the power of a 1D and 2D proton-carbon nuclear magnetic resonance (NMR) in a bench-top instrument that can safely be used in the laboratory. It offers e 1D 1H, 19F and 13C experiments that use standard 5-mm NMR tubes, and 13C experiments that include spectral editing with DEPT, 2D direct HETCOR experiment and 2D indirect experiments such as HMQC and HMBC. Magritek www.magritek.com

Bioreactor system optimizes cell growth Many disposable bioreactors require shakers, rockers, rollers or large environmental chambers. Instead, the CellMaker Plus single-use bioreactor system employs an airlift technology to mix and efficiently aerate the cells, which are grown in single-use, disposable cell culture bags. The bags are efficiently aerated, with controlled air and oxygen flow for optimal cell growth and gentle, effective mixing to maintain cells in suspension.

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System manufactures cellular immunotherapies

The adoption of cell therapy and regenerative medicine requires the development of robust, scalable manufacturing tools and workflows to generate sufficient high-quality cells for infusion into patients. The Xuri Cell Expansion System W25 is suitable for manufacturing cellular immunotherapies in a clinical setting. The functionally closed, automated system is equipped with dedicated software applications to make it suitable for a regulated manufacturing environment.

GE Healthcare www.gelifesciences.com

Hose handles harsh chemical fume extraction

Designed for safe extraction of harsh fumes, the double-ply Flex-Lok TCF Hose is constructed with a black Teflon-coated fabric and a silver heatresistant fiberglass liner mechanically crimped in a continuous process by a metal strip locked around a coated steel wire. It offers good fatigue resistance and is highly flexible. Operates over a -60째F to 600째F range and is a suitable replacement for hard pipe.

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industry news & events News Instrument & Equipment

page 26

Heaters have improved functionality

Techne’s new range of digital Dri-block heaters have a new look and fit a wide selection of instruments. Users can select two-, three- and four-block models for high-throughput applications, as well as a twin control unit for more complex experiments. Integrated timers can be set in one-minute intervals. The outer casing remains cool to the touch even at the maximum operating temperatures of 100˚C and 200˚C. Bibby Scientific www.techne.com

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