Clock Gene Helps Plants Prepare for Spring Flowering, Study Shows

Insight into plants’ body clocks shows how they adjust to changing seasons, causing flowers to bloom in spring.  Insight into plants’ body clocks shows how they adjust to changing seasons, causing flowers to bloom in spring. (Credit: © Peter Wey / Fotolia) University researchers tested computer models of gene networks in a simple cress plant …

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Turning Off Small RNA: New Tool Designed for Breaking the Epigenetic Code

For the last dozen years, scientists have known that minuscule strings of genetic material called small RNA are critically important to our genetic makeup. But finding out what they do hasn’t been easy. Now a scientist from Michigan Technological University and his team have developed a way to turn off small RNAs and find out …

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Biotechnology sector to have more M&A activity due to fund crunch: Report

Paucity of funding for the Indian biotechnology sector for expanding its operations forces it to look towards mergers and acquisitions, according to Yes Bank. The Indian biotechnology sector is not just finding it difficult to raise funds from the public, but also from the private equity sector as well, Yes Bank said in its report …

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A Mitosis Mystery Solved: How Chromosomes Align Perfectly in a Dividing Cell

To solve a mystery, sometimes a great detective need only study the clues in front of him. Like Agatha Christie’s Hercule Poirot and Arthur Conan Doyle’s Sherlock Holmes, Tomomi Kiyomitsu used his keen powers of observation to solve a puzzle that had mystified researchers for years: in a cell undergoing mitotic cell division, what internal …

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Parasites or Not? Transposable Elements in DNA of Fruit Flies May Be Beneficial

Many living organisms suffer from parasites, which use the hosts’ resources for their own purposes. The problem of parasitism occurs at all levels right down to the DNA scale. Genomes may contain up to 80% “foreign” DNA but details of the mechanisms by which this enters the host genome and how hosts attempt to combat …

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Clock Gene Helps Plants Prepare for Spring Flowering, Study ShowsTurning Off Small RNA: New Tool Designed for Breaking the Epigenetic CodeBiotechnology sector to have more M&A activity due to fund crunch: ReportA Mitosis Mystery Solved: How Chromosomes Align Perfectly in a Dividing CellParasites or Not? Transposable Elements in DNA of Fruit Flies May Be Beneficial

Mar 11

Clock Gene Helps Plants Prepare for Spring Flowering, Study Shows

Categories:

Biotechnology

by Steven

Insight into plants’ body clocks shows how they adjust to changing seasons, causing flowers to bloom in spring.

 Insight into plants’ body clocks shows how they adjust to changing seasons, causing flowers to bloom in spring. (Credit: © Peter Wey / Fotolia)

University researchers tested computer models of gene networks in a simple cress plant to determine the role played by a protein, known as TOC1, in governing these daily cycles.

The model shows how 12 genes work together to run the plant’s complex clockwork, and reset the clock at dawn and dusk each day.

Researchers found that the TOC1 protein, which was previously linked to helping plants wake up, is in fact involved in dampening gene activity in the evening.

This helps plants stay dormant at night.

Contradictory finding

“The 24-hour rhythms of biological clocks affect all living things including plants, animals and people, with wide-ranging effects on sleep, metabolism and immunity,” said Professor Andrew Millar of the School of Biological Sciences.

The findings contradict what scientists had previously understood about the gene and its role in early morning activity.

Scientists in Barcelona independently reached a similar conclusion to the Edinburgh team.

The two studies pave the way for further research to define how the cycles improve plant growth and allow plants to adapt to our changing environment.

Changing seasons

These internal 24-hour cycles — known as circadian clocks — also allow people, animals and plants to make tiny adjustments as daylight changes, and adapt to changing seasons.

Researchers hope their discovery will bring them a step closer to understanding other seasonal rhythms that affect plants and people.

These include the flowering of staple crops such as wheat, barley and rice, and the breeding patterns of animals.

“We are now far better placed to understand how this complex process impacts on the plant’s life and what happens when the rhythms are interrupted, for example by climate change,” said Millar.

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Mar 02

Turning Off Small RNA: New Tool Designed for Breaking the Epigenetic Code

Categories:

Biotechnology

by Steven

For the last dozen years, scientists have known that minuscule strings of genetic material called small RNA are critically important to our genetic makeup. But finding out what they do hasn’t been easy. Now a scientist from Michigan Technological University and his team have developed a way to turn off small RNAs and find out just how important they can be.

This illustration shows the traditional view of RNA making proteins, left; how small RNA interferes with protein production, center; and how Tang’s team interfered with the process by introducing a man-made gene to the mix. (Credit: Guiliang Tang illustration)

When it comes to inheritance, DNA is just the half of it. What we are is also driven by the epigenetic world of RNA: the countless, twisting molecules that DNA churns out. RNA in turn transforms the amino acid soup in our cells into the proteins that are us — and every other plant and animal on the planet, for that matter.

There’s more than one kind of RNA, however. In addition to the long strings that make proteins, there are short, meddling snippets called small RNAs. Sometimes, they can attach to long RNA molecules and break them in two. That obviously has consequences for the organism, but exactly what role the thousands of different small RNAs play has been a puzzle.

Now, Guiliang Tang, an associate professor of biological sciences, has developed a way to put a single small RNA out of commission and observe what happens when it can’t do its job.

To do this, Tang and his team threw a wrench into a well-understood process that controls leaf symmetry and the tendency of plants to grow upright.

First they synthesized a sequence of DNA that would make a custom-designed type of small RNA, called a small tandem target mimic, or STTM. Then they introduced their synthetic DNA in Arabidopsis, a plant often used in genetics research. Once in the Arabidopsis, the synthetic DNA began manufacturing many copies of the STTM.

Then all the little STTMs began locking onto strands of a specific type of RNA, right where the plant’s small RNA would normally have cut them in two. That blocked its action, so the long RNA strands remained intact.

Furthermore, the procedure prompted the cell to destroy all of its own small RNAs that would normally have cut the RNA. Together, those two mechanisms allowed the long RNA to make its protein unabated.

The results were dramatic. The control Arabidopsis plants grew upward on a central stem with regularly shaped leaves and stems. The mutant plants were smaller, tangled, and amorphous.

Their method isn’t limited to one small RNA involved in leaf symmetry in Arabidopsis.

“You can use this to study the function of any small RNA in the cell,” says Tang.

In an online commentary, Plant Cell senior features editor Nancy Eckardt called their method “a highly effective and versatile tool” for studying the functions of small RNA.

Now, Tang hopes to find out how and why this procedure causes cells to destroy small RNA. And his wife and fellow researcher Xiaoqing Tang, an assisant professor of biological sciences, plans to use this technology to better understand type 2 diabetes.

Their work is funded by the National Science Foundation and described in the article “Effective Small RNA Destruction by the Expression of a Short Tandem Target Mimic in Arabidopsis,” published Feb. 16 online in the journal Plant Cell. The lead authors of the paper are students who worked with Tang: Jun Yan, now a postdoctoral researcher at Purdue University, and Yiyou Gu, now an undergraduate at Nanjing Agricultural University, in China. Other coauthors are Xiaoyun Jia, Wenjun Kang and Shangjin Pan of the University of Kentucky and Xuemei Chen of the University of California at Riverside.

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Feb 15

Biotechnology sector to have more M&A activity due to fund crunch: Report

Categories:

Biotechnology

by Steven

Paucity of funding for the Indian biotechnology sector for expanding its operations forces it to look towards mergers and acquisitions, according to Yes Bank.

The Indian biotechnology sector is not just finding it difficult to raise funds from the public, but also from the private equity sector as well, Yes Bank said in its report on biotech industry, titled ‘Indian Biotechnology Ecosystem- an Investment Perspective’.

“Further, the investments, which are made, will be in several tranches tied to milestone payments and not in lump-sum, as was wont to be the case earlier. However, Yes Bank expects the M & A activity in the sector to see a significant rise, as small niche companies exhaust their cash surpluses and start exploring new models for restructuring their business, the report said.

Most investors are unwilling to invest in Life Science companies’ R & D activities, as they prefer funding companies, whose product and market are clearly identified, forcing Life Science entrepreneurs to be unable to raise sufficient funds for basic R & D through equity investments, it says.

“The current conservative investor mindset is resulting in Indian investors looking to fund matured companies. Most of the deals done over the last few years have been for manufacturers of generic drugs or contract manufacturers, as these are perceived as fairly low-risk businesses,” it further said.

The Bank opined that a majority of the IPOs will be from the pharmaceutical sector, as most companies in the biotech and medical devices sectors in India are still at a nascent stage as the recent years have not been successful for Life sciences IPOs owing to the current weak market conditions and global economic cues.

The situation has led to a huge gap between the companies’ expected valuations and those arrived at by the investor community.

Within the Life Sciences Industry, Biotechnology has been identified as a key area of growth with the Global biotechnology market predicted to surpass $ 320 billion by 2015.

The global Biotech industry is lead by US, followed by advanced European countries. Developing countries such as India and China are soon emerging as major Biotechnology markets, according to the report.

Indian Biotech market has tripled over the last five years, and is projected to grow at a CAGR of over 20 per cent to achieve a market size of $ 8 billion by 2015.

The global biotech market for 2010 is around $ 85 billion and is expected to reach $ 320 billion by 2015. There has been a large gap between the funding available for this sector and the funding required by the players to achieve their full potential, it said

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Feb 12

A Mitosis Mystery Solved: How Chromosomes Align Perfectly in a Dividing Cell

Categories:

Biopharmaceuticals, Biotechnology, Pharmaceutical

by Steven

To solve a mystery, sometimes a great detective need only study the clues in front of him. Like Agatha Christie’s Hercule Poirot and Arthur Conan Doyle’s Sherlock Holmes, Tomomi Kiyomitsu used his keen powers of observation to solve a puzzle that had mystified researchers for years: in a cell undergoing mitotic cell division, what internal signals cause its chromosomes to align on a center axis?

 ”People have been looking at these proteins and players in mitosis for decades, and no one ever saw what Tomomi observed,” says Whitehead Institute Member Iain Cheeseman. “And it’s very clear that these things are happening. These are very strong regulatory paradigms that are setting down these cell division axes. And careful cell biology allowed him to see that this was occurring. People have been looking at this for a long time, but never with the careful eyes he brought to it.”

Kiyomitsu, a postdoctoral researcher in Cheeseman’s lab, published his work in a recent issue of the journal Nature Cell Biology.

The process of mitotic cell division has been studied intensely for more than 50 years. Using fluorescence microscopy, today’s scientists can see the tug-of-war cells undergo as they move through mitosis. Thread-like proteins, called microtubules, extend from one of two spindle poles on either side of the cell and attempt to latch onto the duplicated chromosomes. This entire “spindle” structure acts to physically distribute the chromosomes, but it is not free floating in the cell. In addition to microtubules from both spindle poles that attach to all of the chromosomes, astral microtubules that are connected to the cell cortex — a protein layer lining the cell membrane — act to pull the spindle poles back and forth within the cell until the spindle and chromosomes align down the center axis of the cell. Then the microtubules tear the duplicated chromosomes in half, so that ultimately one copy of each chromosome ends up in each of the new daughter cells.

The process of mitosis is extremely precise; when it comes to manipulating DNA, cells verge on being obsessive and with good reason. Gaining or losing a chromosome during cell division can lead to cell death, developmental disorders, or cancer.

As Kiyomitsu watched mitosis unfold in symmetrically dividing human cells, he noticed that when the spindle oscillates toward the cell’s center, a partial halo of the protein dynein lines the cell cortex on the side farther away from the spindle. As the spindle swings to the left, dynein appears on the right, but when the spindle swing to the right, dynein vanishes and reappears on the left side.

For Kiyomitsu, the key to the alignment mystery was dynein, which is known as a motor protein that “walks” molecular cargoes along microtubules. Kiyomitsu determined that in this case, dynein is anchored to the cell cortex by a complex that includes the protein LGN, short for leucine-glycine-asparagine-enriched protein. Instead of moving along an astral microtubule, the stationary dynein acts as a winch to pull on the spindle pole, and the microtubules and chromosomes attached to it, toward the cell cortex.

Kiyomitsu found that when a spindle pole comes within close proximity to the cell cortex, a signal from a protein called Polo-like kinase 1 (Plk1) emanates from the spindle pole, knocking dynein off of LGN and the cell cortex, stopping the spindle pole’s forward motion, and freeing dynein to move to the opposite side of the cell. These oscillations continue with decreasing amplitude until the spindle settles along the cell’s center axis.

As he was deciphering dynein’s role in spindle alignment, Kiyomitsu noticed that a layer of LGN extends all around the cell cortex, except in the areas that are closest to the chromosomes. As the chromosomes swing back and forth, the area cleared of LGN changes in response. Because dynein needs to anchor to LGN, this cleared area ensures that dynein can only attach and pull to the right and left of the aligning chromosomes, rather than from above and below.

After testing a couple of signaling molecules associated with chromosomes, Kiyomitsu determined that a signal from the chromosomes, involving the ras-related nuclear protein (Ran), blocks LGN, and therefore dynein, from attaching to the cell cortex closest to the chromosomes. Ran bound to guanosine-5′-triphosphate (Ran-GTP), which controls nuclear import in the interphase stage of mitosis, had previously been suggested to control spindle assembly during mitosis in germ cells, but roles for the Ran gradient in mitotic non-germ cells were unclear. Kiyomitsu’s work suggests a key role for Ran in directing spindle orientation.

Kiyomitsu says the axis that the spindle poles travel along is crucial to cells.

“The spindle orientation is critical for maintaining the balance between stem cells and mature cells during development,” he notes. “And if this orientation becomes dysregulated or misregulated, it is reported that this may contribute to causing cancer even if chromosomes are properly segregated.”

This work was supported by the Massachusetts Life Sciences Center, the Searle Scholars Program, and the Human Frontiers Science Foundation, the National Institutes of Health (NIH)/National Institute of General Medical Sciences, and the American Cancer Society.

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Feb 05

Parasites or Not? Transposable Elements in DNA of Fruit Flies May Be Beneficial

Categories:

Biotechnology

by Steven

Many living organisms suffer from parasites, which use the hosts’ resources for their own purposes. The problem of parasitism occurs at all levels right down to the DNA scale. Genomes may contain up to 80% “foreign” DNA but details of the mechanisms by which this enters the host genome and how hosts attempt to combat its spread are still the subject of conjecture. Important new information comes from the group of Christian Schlötterer at the University of Veterinary Medicine, Vienna.

The findings are published in the journal PLoS Genetics.

Nearly all organisms contain pieces of DNA that do not really belong to them. These “transposable elements,” so called because they are capable of moving around within and between genomes, generally represent a drain on the host’s resources and in certain cases may lead directly to disease, e.g. when they insert themselves within an essential host gene. The factors that govern the spread of transposable elements within a population are broadly understood but many of the finer points remain unclear. New work at the University of Veterinary Medicine, Vienna (Vetmeduni Vienna) may pave the way to a more profound knowledge of the intracellular battle that is constantly being played out between the host and invading DNA.

Robert Kofler and Andrea Betancourt in Schlötterer’s group at the Vetmeduni Vienna’s Institute of Population Genetics used new sequencing technologies to examine the variation in transposable elements within a population of fruit flies. Similar investigations had been undertaken previously but the scientists incorporated a number of refinements to ensure that their analysis considered both known and previously unknown sites of insertion. For the first time, the researchers were able to catalogue all the transposable elements in a population of flies. And importantly they were also able to determine how frequently transposable elements occur at each particular site of insertion.

The findings were dramatic. The flies contain transposable elements at a large number of sites in the genome, although many insertion sites are affected in relatively few individuals. These are presumably sites of recent insertion and only the future will tell whether the elements are maintained there. Some older insertion sites are widespread but the majority seem not to be “fixed” in the population. In other words, most transposable elements are somehow purged before they become established. Schlötterer sums up the results by stating that “the genome is like a record of past wars between hosts and the parasitic DNA. There have been waves of attacks and the majority of them have been repelled, with only few transposable elements managing to survive and spread throughout the population.”

Even more surprisingly, the scientists found about a dozen sites of insertion that were more frequent in the population than would be expected from their age (assessed via a different method). It seems, then, that there is positive selection for transposable elements at these sites, suggesting that insertion has a beneficial effect on the host. Such an effect had previously been shown for two insertions that give increased resistance against insecticides and these cases were refound by Schlötterer’s analysis. The functions of the genes closest to the remaining insertions are highly diverse, so how the transposable elements may benefit the flies is unclear. As Schlötterer puts it, “perhaps we shouldn’t really think of transposable elements as parasites at all. They represent a way for organisms to increase their genetic repertoire, which may be advantageous in helping them meet future challenges.” 

Source:  http://www.sciencedaily.com

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Aug 25

Seminar tackles biotech crop facts

Categories:

Biotechnology

by Steven

MANILA, Philippines — There is nothing to fear about Bacillus thuringiensis (Bt) eggplant, delayed ripening papaya and Golden Rice.

This claim will be backed up with scientific facts by advocates of biotech crops in a seminar Friday, at the Southeast Asian Regional Center for Graduate Study and Research in Agriculture (SEARCA) at the UP Los Baños campus in Laguna.

At least 80 students and teachers from various schools will be attending the seminar organized by UP Los Baños-Office of the Vice Chancellor for Research and Extension (OVCRE), Crop Protection Cluster, the National Institute of Molecular Biology and Biotechnology (BIOTECH), Biotechnology Coalition of the Philippines (BCP), Biotech Media and Advocacy Resource Center (BMARC), Jose Burgos Media Services, Program for Biosafety Systems Philippines (PBS) and the SEARCA Biotechnology Information Center (BIC.)

The seminar starts at 3 p.m. and ends at 5 p.m.

Dr. Reynaldo V. Ebora, director of UPLB BIOTECH, will welcome the seminar participants while Abraham J. Manalo, BCP executive secretary, and UPLB Chancellor Dr. Luis Rey I. Velasco will deliver messages.

Manalo is a policy and planning specialist whose work includes agricultural policy, biotechnology and biosafety, government reorganization and development planning.

He has wide experience in providing management and technical support in coordinating activities related to policy formulation, institutional strengthening, constituency building, information, education and communication (IEC) and public awareness.

Dr. Evelyn Mae Tecson-Mendoza of the UPLB-Institute of Plant Breeding (IPB) will provide updates on transgenic papaya with delayed ripening trait in her capacity as project leader.

For Bt eggplant, which is being tested at UPLB, Dr. Desiree M. Hautea will be the main discussant.

She is the regional coordinator of the Agricultural Biotechnology Support Project II at UPLB-IPB.

Dr. Antonio A. Alfonso, chief science research specialist at the Philippine Rice Research Institute (PhilRice), will tackle the immense potential of Golden Rice to address the worsening vitamin A deficiency in the Philippines, which afflicts up to 19 million children and 1.9 million lactating mothers.

PhilRice is also working on Golden Rice strains that resist tungro and leaf blight, which are two major problems among rice growers.

BMARC executive director Dr. Edita T. Burgos will deliver the closing remarks.

Jenny A. Panopio of SEARCA BIC and Carlo Custodio Jr. of PBS will be the moderators.

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Aug 10

New Tools Permit Delicate Manipulation of the Stem Cell Genome

Categories:

Biochemistry, Biopharmaceuticals, Biotechnology, Medicine, Pharmaceutical

by Steven

Researchers have compared the effectiveness of two methods for modifying the genomes of human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells.

Investigators at the Whitehead Institute (Cambridge, MA, USA) initially employed zinc finger nucleases (ZFNs) to modify a single base pair in the iPS genome. Zinc-finger nucleases (ZFNs) are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain. Zinc finger domains can be engineered to target desired DNA sequences, and this enables zinc-finger nucleases to target unique sequences within complex genomes. By taking advantage of endogenous DNA repair machinery, these reagents can be used to precisely alter the genomes of higher organisms.

The modification, as described in the July 14, 2011, online edition of the journal Cell, was either the insertion or deletion of the mutation that causes early-onset Parkinson’s disease (PD). This technology allowed the researchers to study the same cell line in both a normal and diseased state.

In a parallel study published in the July 7, 2011, online edition of the journal Nature Biotechnology the investigators used an entirely different technique to modify the genome. Here they used transcription activator like effector nucleases (TALENs) instead of ZFNs. They reported that TALENs – employing the specific architectures described in their study – mediated site-specific genome modification in human pluripotent cells with similar efficiency and precision, as did ZFNs.

Both the ZFNs and the TALENs used in these studies were produced by Sangamo BioSciences (Richmond, CA, USA).

“It is very important that the cells be genetically identical and have the same history, then make or remove only that mutation,” said senior author Dr. Rudolf Jaenisch, professor of biology at the Whitehead Institute. “If you use control cells from one person and a diseased cell from another person, it is like comparing apples and oranges. This is very relevant for diseases like Parkinson’s, which likely will display only subtle phenotypes in the Petri dish. ”

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Jul 29

Bio-Based Economy Central to Europe’s 2020 Vision

Categories:

Biotechnology

by Steven

London, UK, July 28, 2011 - Nathalie Moll, Secretary General of EuropaBio, talks about the role of industrial biotechnology in Europe and EuropaBio’s European Forum for Industrial Biotechnology and The Bio-based Economy.

Industrial biotechnology’s far-reaching potential needs to be matched by appropriate government support in order to ensure its role in meeting society’s grand challenges of limiting the impact of climate change, reducing fossil fuel dependency and creating a smarter, more sustainable economy for Europe.

According to Nathalie Moll, Secretary General of EuropaBio, these issues will continue to fuel debate at this year’s European Forum for Industrial Biotechnology and The Bio-based Economy (EFIB), Europe’s leading event in this field, which has become the well-established meeting place for policy and business.

Organised by EuropaBio, in partnership with IntertechPira, this year’s forum will take place in Amsterdam from October 19th to 20th and will bring together policy makers, NGOs, academics and industry stakeholders to evaluate the evolving political and economic context and growing significance of the industrial biotechnology sector. As well as facilitating communication and knowledge transfer between key players in the industrial biotech sector, EFIB 2011 will cover key issues such as end-user perspectives and market forecasts; challenges to financing a global bio-based economy; the bio-based economy in the context of the Common Agricultural Policy reform; the bioplastics industry and the critical role played by supportive innovation and funding policy at an EU level.

Moll says: “Part of the appeal of industrial biotechnology is that, in addition to meeting commercial needs, it also creates smart, sustainable and integrated products with reduced impact on the environment. These range from more sustainable industrial processes to everyday consumer benefits such as washing powders that enable users to clean clothes at lower temperatures, making big energy savings.”

Moll believes that there has been clear recognition in the last few years by the European Commission of the important role industrial biotechnology plays in stimulating expansion of the EU economy in a sustainable manner. EuropaBio is extremely encouraged by the strong response and leadership from Commissioner Geoghegan-Quinn and her peers, she says, commenting: “The attention that the Commission is giving to biotechnology as a whole and in particular to industrial biotech in the context of the upcoming Horizon 2020 programme as well as of the Knowledge-Based Bio-Economy Strategy clearly highlights this technology’s role in supporting the European economy in the smartest, most sustainable and inclusive manner.”

However, with the US, Asia and South America committing to long term research and funding of the biotech sector and its applications, Europe will need to introduce even greater incentives to create a level playing field for bio-based products and enable the market penetration required for Europe’s bio-based economy to succeed in the coming years. “In order to be successful and competitive with the rest of the world, Europe needs to stimulate market demand. To do this we need not only to improve communication throughout the value chain and with end consumers about the role and benefits of industrial biotech applications, we also need supportive and coherent policy, incorporating incentives at EU and national level to stimulate the uptake of bio-industrial processes in our industries and in our day to day lives,” she added.

About EuropaBio EuropaBio’s mission is to promote an innovative and dynamic biotechnology based industry in Europe. EuropaBio, (the European Association for Bioindustries), has 66 corporate and 7 associate members operating worldwide, 4 Bioregions and 22 national biotechnology associations representing some 1800 small and medium sized enterprises. About

IntertechPira IntertechPira provides events, market research, publications, strategic and technical consulting to niche, emerging and high growth industries. Market coverage includes industrial biotechnology, lighting and displays, clean energy, home and personal care, performance materials and chemicals. IntertechPira is a division of Pira.

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Jul 08

Nano Detector for Deadly Anthrax

Categories:

Biotechnology

by Steven

An automatic and portable detector that takes just fifteen minutes to analyze a sample suspected of contamination with anthrax is being developed by US researchers. The technology amplifies any anthrax DNA present in the sample and can reveal the presence of just 40 microscopic cells of the deadly bacteria Bacillus anthracis.

B. anthracis, commonly known as anthrax, is a potentially lethal microbe that might be used intentionally to infect victims through contamination of food and water supplies, aerosolized particles, or even dried powders, such as those used in bioterrorist attacks in the USA. Detection is crucial to preventing widespread fatalities in the event of an anthrax attack. However, the complexity of the microbe’s biology have so far made it difficult to build a portable system that can be employed quickly in the field. That said, there are several systems available that use PCR to amplify a particular component of the genetic material present in anthrax and then to flag this amplified signal. These systems are fast and sensitive but do not integrate sample preparation and so are not as convenient as a single detector unit would be.

Writing in the International Journal of Biomedical Nanoscience and Nanotechnology this month, Nathaniel Cady of the College of Nanoscale Science and Engineering (CNSE) of the University at Albany and colleagues there and at Cornell University, New York, explain how they have constructed nanofabricated fluidic cartridges that can be used to carry out detection of anthrax. The device is a so-called “lab-on-a-chips” device, or more properly a 3D microfluidic network that contains nanofabricated pillar structures.

The device has fluidic inputs for adding sample and reagents, removing waste, for carrying out DNA purification, and critically an integrated chamber for amplifying only the target DNA in the sample using the polymerase chain reaction (PCR) system. The chip also contains a wave guide for the fluorescence-based identification of the amplified DNA and thus the target microbe. Importantly, the system works without manual intervention other than loading a droplet of sample into the detector.

“The average time required for DNA purification during these experiments was approximately 15 min, and when combined with real-time PCR analysis, this resulted in an average time to detection of 60 min,” the team says. The system can detect as few as 40 B. anthracis cells. “Due to its small size and low power requirements, this system can be further developed as a truly portable, hand-held device,” the researchers conclude.

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Jun 21

FDA Tries to Address Some Concerns Over Nanotech in Biotech

Categories:

Biotechnology

by Steven

More details are needed, but developers now have a better idea of what constitutes nanomaterials.

 

The naked eye cannot see particles that are a billionth of a meter, or a nanometer. Yet the FDA is trying to get its arms around them, so to speak, in hopes of defining for biotechnology companies and others whether FDA-regulated products contain nanomaterials or otherwise involve the application of nanotechnology.

FDA recently issued a draft guidance titled “Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology” and has launched a 60-day comment period on it. “The guidance is intended to help industry identify when they should consider potential implications for regulatory status, safety, effectiveness, or public health impact that may arise with the application of nanotechnology in FDA-regulated products,” Jeff Ventura, an FDA spokesman, told GEN.

In the draft guidance, FDA stated that it will determine whether products contain nanomaterials or involve the application of nanotech by their properties and size. FDA will ask whether engineered materials or their end products have at least one dimension ranging from 1 to 100 nm. The agency will also check whether they exhibit physical or chemical properties or biological effects attributable to its dimensions, even if they fall outside the nanoscale range, going up to one micrometer.

The agency noted that it may issue further guidance to address considerations for specific products or classes of products. “The critical element is that size matters in biological systems,” Frank J. Malinoski, M.D., Ph.D., CMO for Liquidia Technologies, told GEN. “We need to know which sizes are important for which biological or chemical effects.”

The Push to Regulate

In May 2006, the International Center for Technology Assessment and Friends of the Earth presented the FDA with a citizen petition to require labeling of all nanomaterials in consumer products. Then on October 5, 2006, the Woodrow Wilson Center for International Scholars issued a report by former FDA deputy commissioner for policy Michael Taylor, which concluded the agency lacked the legal tools, let alone the resources, needed to regulate nanotech products, especially in cosmetics and dietary supplements. Taylor is now deputy commissioner for foods at the FDA.

Five days after Taylor’s report, FDA convened the first meeting of the the Nanotechnology Task Force, which had been set up earlier that year. It found that the agency needed to improve its scientific knowledge of nanotech and needed to evaluate current tools for describing and evaluating nanoscale materials. The task force, however, offered little in the way of guidance except for the meek conclusion stating that there was a need for “timely development of a transparent, consistent, and predictable regulatory pathway.”

FDA released its first “draft guidance” on June 9 of this year, the day three Obama administration agencies—the offices of Management and Budget, of Science and Technology Policy, and of the U.S. Trade Representative—put out a set of policy principles for regulating and overseeing nanotechnology and nanomaterials.

The heads of all three agencies included in the principles a subtle pitch for President Obama’s plan to boost spending for the National Nanotechnology Initiative (NNI), calling it “one of the Obama Administration’s top science and technology priorities.”

NNI coordinates the individual and cooperative nanotechnology-related activities of 25 federal agencies. Its budget is the sum of the R&D budgets of 15 agencies. It has spent $14 billion on nanotech R&D since the 2001 fiscal year. NNI saw funding dip under the FY 2011 budget agreement crafted in April to $1.76 billion from $1.9 billion in FY 2010.

President Obama has proposed $2.1 billion for NNI in his $3.8 trillion budget for the fiscal year starting Oct. 1. The prospects of that happening are uncertain at best; the budget won’t be decided until Congressional leaders hash out spending cuts to eliminate now-annual trillion-dollar deficits. So far, that process has yielded little more than Obama’s proposed budget, the Republican-approved deficit reduction plan unveiled by Rep. Paul Ryan (R-WI), and much partisan sniping.

Agency’s Definition of Nanotech

The draft stated, “A range of approximately 1 nm to 100 nm should be applied as a first reference point in considering whether an FDA-regulated product contains nanomaterials or otherwise involves application of nanotechnology.”

Nanomaterials could also be larger or combine into agglomerates that exceed 100 nm. FDA addressed that as well in the draft guidance: “The agency considers that an upper bound of up to one micrometer (i.e., 1,000 nm) would serve as a reasonable parameter for screening materials with dimensions beyond the nanoscale range for further examination to determine whether these materials exhibit properties or phenomena attributable to their dimension(s) and relevant to nanotechnology.”

“A lot of the products that the FDA would have jurisdiction under, a lot of those products have agglomerates of nanomaterials in the final product,” Todd Kuiken, Ph.D., research associate for the Project on Emerging Nanotechnologies at the Woodrow Wilson Center for International Scholars, pointed out to GEN.

James R. Baker Jr., M.D., CEO and founder of NanoBio®, offered this perspective to GEN: “Practically, it helps to clarify things by defining a little more broadly what they’re considering. But for a company like us, we have to go through standard toxicity testing, so it really doesn’t change the game.”

Founded in 2000 as a spin-out from the Center for Biologic Nanotechnology at the University of Michigan, NanoBio develops and commercializes dermatological products, anti-infective treatments, and intranasal vaccines, all based on its NanoStat™ platform.

Last month NanoBio reported the start of two Phase III multicenter trials evaluating its NB-001 as a topical treatment for cold sores, a step forward in the company’s OTC licensing agreement with GlaxoSmithKline Consumer Healthcare. The trials of NB-001 will be conducted in 1,700 subjects at 72 clinical sites and will evaluate the effectiveness of NB-001 to reduce cold sore healing time. The trials are expected to conclude next year.

Dr. Baker said the draft guidance’s acknowledgement that nanomaterials may be larger than 100 nm would prove helpful to many businesses. NanoBio’s NanoStat platform, for one, uses high-energy, oil-in-water emulsions manufactured at 150–400 nm and stabilized by surfactants.
More to Be Considered

“There is no one nanotechnology,” Dr. Baker asserted. “Thus nanomaterials, even in the same size range, act very differently. Essentially, they’re just going to have to consider these one-on-one and not make any blanket statements about them.”

Dr. Malinoski of Liquidia added: “One of the critical elements will be, ‘How well can we measure those? How reproducibly? What’s your distribution of particles, and what do different particle sizes do to affect the biological result you’re trying to achieve? How can you distinguish something 10 from something 20, 40, 60, 100 nanometers?”

Also very important, Liquidia chairman Seth Rudnick, M.D., added, is shape. FDA addressed this by saying “manufacturing changes alter the dimensions, properties, or effects of an FDA-regulated product or any of its components.”

Dr. Rudnick remarked, “all of us are trying to define what is a nanostructure that is biologically relevant and important. That probably will be dependent on both size and shape, something we think Liquidia is uniquely positioned to be able to explore but that other companies will be exploring with the agency over the next few years.”

Liquidia is a developer of vaccines based on engineered particles capable of delivering small molecule and biologic therapies to an intended target. Its platform technology is called Particle Replication in Non-Wetting Templates. Those particles can range from tens of nanometers to hundreds of microns.

Liquidia reportedly established a dialogue with agency regulators as it was developing its technologies, starting with lead candidate LIQ001, a seasonal flu vaccine. LIQ001 began Phase I testing last year. “Our first IND was submitted, went through without any regulatory stops, so that we got from concept into the clinic in 18 months,” Dr. Malinoski said. “And part of that was because we saw the need to be proactive and to help educate those reviewers at the agency who were looking at this nanotechnology for the first time.”

FDA hopes other companies follow suit, whether or not they are pursuing required premarket reviews. “Where products applying nanotechnology are not subject to premarket review, the agency urges manufacturers to consult with the agency early in the product development process. In this way, any questions related to the regulatory status, safety, effectiveness, or public health impact of these products can be appropriately and adequately addressed,” the draft guidance advised.

As FDA acknowledges, the draft guidance is just the beginning of its thinking on how to ensure that nanotech-based products are safe and effective. To the extent they address these two qualities, the guidance should provide a valuable roadmap for nanotech-based drug development.

A heavier-than-needed hand by FDA when it comes to regulation, however, creates potential for something else: as Dr. Malinoski put it, “getting so bogged down in guidances that we focus on guidance instead of bringing new products forward.”

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