Biotech/Nanotech Synergy

Public release date: 13-Aug-2003
Contact: Barb Abney
bcompton@mail.ucf.edu
407-823-5139
University of Central Florida

UCF brain cell research spawns hope for longer life
University of Central Florida researchers find that nanomaterials developed for industry triple or quadruple life of brain cells

ORLANDO, Aug. 13, 2003 -- A molecular biologist and a nanoscientist at the University of Central Florida have found that nanomaterials developed for industry have an unexpected and potentially revolutionary side effect: They can triple or quadruple the life of brain cells.
The result is people could live longer and with fewer age-related health problems.

Beverly Rzigalinski, assistant professor in the Department of Molecular Biology and Microbiology and at the Biomolecular Sciences Center, and Sudipta Seal, associate engineering professor at the Advanced Materials Processing and Analysis Center and the Department of Mechanical, Materials and Aerospace Engineering, will receive $1.4 million from the National Institutes of Health, National Institute on Aging to study the reasons behind the reaction and possible future applications.

Rzigalinski has spent the bulk of her career on NIH-funded research from the National Institute of Neurological Disorders and Stroke studying how brain cells "talk" to each other, most recently focusing on microglia -- a specialized cell that responds to brain injury and initiates the response to either repair or destroy the damaged neuron. Seal creates nanostructure materials and recently developed a process for engineering particles on a nanoscale -- so they might have more efficient industrial applications.

Because of the current flurry of publicity that anti-oxidants have received for their potential anti-aging properties, Rzigalinski decided to explore introducing the miniaturized particles to the brain cells of rats.

"In culture, rat brain cells usually live about three weeks," Rzigalinski said. "The cells exposed to the engineered nanoparticles lived three to four times longer."

To confirm the results, Rzigalinski, the grant's principal investigator, repeated the process multiple times and found that cells exposed to a single dose of engineered nano-oxide particles routinely outlived the untreated cells by three- to four-fold, with the longest living cell lasting 123 days.

Rzigalinski then explored the quality of the aged neurons and found they were signaling or "talking" to each other in the same manner as their youthful counterparts. "This shows there is a potential not just to extend the life span but to preserve function," she said.

Seal has worked on developing oxide particles for high temperature production since his undergraduate days in the late 1980s. In 2000, as he took over the coordination of UCF's nanotechnology initiative, he and a student developed ultrafine nano-sized powders and solutions. The particles, less than 10 nanometers (about 30 atoms) in size, not only offered a more efficient coating for use in machines but also opened the door for biological studies in collaboration with Rzigalinski.

When a university research administrator aware of the work of each scientist introduced the two, the possibilities immediately began forming. "This type of cross-disciplinary partnership is what we dream about," said Pallavoor Vaidyanathan, assistant vice president for research. It is also critical to forging frontiers in nanoscience.

Research in the medical profession suggests that a major component of aging is free radical damage to cells. Free radical scavengers, often taken in the form of vitamins, can counter the damage to a very limited degree. A regenerative nanoparticle, such as the one developed by Rzigalinski and Seal, offers promise of negating those problems and could be helpful in treatment of certain age-related disorders -- such as Alzheimer's disease -- as well as arthritis and other joint-related problems, Rzigalinski says.

Most recently, the Rzigalinski lab has found that the nanoparticles have potent anti-inflammatory properties. The investigators plan to explore the possibility of creating a coating from the particles that could be used for vascular and orthopedic implants, stents and other devices that are prone to inflammatory reactions.

Initial tests show that the nanoparticle anti-oxidants regenerate once they penetrate the cell -- meaning one dose could conceivably continue its therapeutic effects indefinitely.

Rzigalinski introduced the collaboration to her colleagues at the NATURE biotechnology symposium in Miami earlier this year. She has also submitted an abstract on the project to the National and International Neurotrauma Symposium, and Society for Neuroscience.

Nanotechnology is considered the new frontier of science, and it could revolutionize modern medicine in the future. The potential for creating new materials at a size capable of being absorbed by human cells calls for a new type of scientist -- one who can collaborate across seemingly unrelated disciplines. Combining the fields of biomolecular science with engineering offers a significant step in that direction.

Pappachan Kolattukudy, director of UCF's Biomolecular Science Center and a consultant on the project, said the collaboration is part of a strategy that UCF is going to be using increasingly in building its presence in the biomolecular sciences.

"We are concentrating on building interfaces between areas in which we have strengths," Kolattukudy said.

Vimal Desai, director of AMPAC, said that nanomaterials are currently considered highly strategic for important applications ranging from homeland security to just plain good health.

"It is so good to be able to build bridges for an interdisciplinary effort through competent and dynamic researchers at UCF," Desai said.


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Here is another article that I am putting here in Biotech but also could be posted undernanotech. The procedure used is one tha twill offer much information in the future but these results from this first application deserve close scrutiny to those interested in how the brain and neurons function.

http://story.news.ya...90534&e=4&ncid=
Nanotech breakthrough shows how brain cells chatter
Thu Oct 16, 3:05 PM ET Science - AFP

PARIS (AFP) - French scientists using an innovative microscopic scanning technique say they have discovered that nerve cells almost buzz with molecular agitation when they communicate with each other.

The work sheds light on how cells operate at the synapse -- the minute gap between neurons, as nerve cells are called.

Neurons communicate by sending chemical signals across the synapse, which then latch on to specific targets, known as receptors, on the membrane of the adjoining cell.

The chemicals activate an electrical signal in that cell, which then sends on a chemical signal to its neighbour, and so on down the line, eventually triggering the desired response or movement in the finger, hand, limb or other organ.

Until now, little was known about receptor movement, and it was thought that these vital "locks" that open to the heart of the cell were largely static.

But nanotechnology, harnessed to a video camera by French researchers, shows the receptors to be extraordinarily active and that they even move around dynamically on the membrane surface.

The discovery is important, because it highlights the complex, highly mobile mechanism by which a receiving cell is able to detect just a single molecule.

The team, led by Antoine Triller, head of an Inserm unit that specialises in synapse research, and Maxime Dahan, of the Kastler Brossel Laboratory at Paris's Ecole Normale Superieure, publishes its work in Friday's issue of Science, the US scientific weekly.

Their observations were made on spinal cord tissue from rats, and used a probe called quantum dots -- fluorescent semiconductors, with a cadmium-selenium core and a zinc sulphide shell -- to tag receptors for glycine, a key synapse signalling chemical.

The "dots" measure just five to 10 billionths of a metre across, and are just a quarter of the smallest nanoparticle tracers used so far. Those particles, made of gold or latex, range from 40 to 500 billionths of a metre, which means they are too big to reveal the single-molecule properties of living cells.

The movement given by the fluorescing quantum dots was filmed in real time, and for long durations, using a videomicroscope.

Link: http://www.eurekaler...r-iaf102303.php
Date: 10-23-03
Author: Susan Edmonds sedmonds@fhcrc.org 206-667-2896 Fred Hutchinson Cancer Research Center
Source: Fred Hutchinson Research Center
Title: Intel and Fred Hutchinson to explore the use of nanotechnology tools for early disease detection

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Intel and Fred Hutchinson to explore the use of nanotechnology tools for early disease detection
The Intel Raman Bioanalyzer System™ to help researchers understand the molecular differences between healthy cells and diseased cells for better diagnostic methods
STANFORD, Calif., Oct. 23, 2003 - Intel Corporation and the Fred Hutchinson Cancer Research Center today announced a collaborative research effort to apply Intel's expertise in nanotechnology to develop improved methods of studying, diagnosing and preventing cancer. The announcement was made at the BioSilico Seminar, held at Stanford University.

"To launch the effort, Intel is building an Intel Raman Bioanalyzer System at the Fred Hutchinson Cancer Research Center in Seattle," said Andrew Berlin, lead researcher, Intel's Precision Biology program. "The instrument beams lasers onto tiny medical samples, such as blood serum, to create images that reveal the chemical structure of molecules. The goal is to determine if this technology, previously used to detect microscopic imperfections on silicon chips, can also detect subtle traces of disease."

"This collaboration is a unique and exciting interaction," said Dr. Lee Hartwell, Nobel Laureate and center president and director. "Biologists have never before had such a method for studying the molecular structure of biology. This is true discovery-based research; we don't know what we will see or learn. It may lead to a new era of molecular diagnostics and improved methods of early disease detection."

"Intel enthusiastically endorses Dr. Hartwell's vision of Early Disease Detection and I am thrilled to have this opportunity to help accelerate progress towards it realization. This is collaborative research at its best. Together we can learn how best to adapt advances in nanotechnology to solve some of the most pressing problems in medicine and biology," said David Tennenhouse, vice president, Intel's Corporate Technology Group and director of research.

The Intel Raman Bioanalyzer System is based on a technique known as Raman spectroscopy Intel uses this technique to analyze subtle chemical compositions during the chip fabrication process. By shining a laser beam at an object, molecules within the substance are stimulated to give off a spectrum that can be detected by sensors in a Raman spectrometer. Because every substance has a unique chemical composition, every substance produces a unique Raman spectrum - the equivalent of a chemical barcode tag.

At the Fred Hutchinson Cancer Research Center, medical researchers hope the specially designed instrument - the most sensitive of its kind in the world - will help them identify proteins in human blood serum that foretell the susceptibility, presence or prognosis of diseases such as cancer. At the same time, Intel will learn from them about potential applications and benefits of the technology.


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Intel's Precision Biology Program
Precision Biology is a research team of chemists, engineers, biologists and physicists. They combine expertise in microbiology and molecular analysis with Intel's core expertise in microelectronics, MEMS and nanotechnology. The team is conducting long-range research to create fundamental advances in sensor technology, and to work together with the medical community to make it possible to one day use chips to diagnose disease and improve peoples' health.

Fred Hutchinson Cancer Research Center
The Fred Hutchinson Cancer Research Center, home of two Nobel Prize laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical research to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, the University of Washington and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 39 nationwide. For more information, visit the center's Web site at http://www.fhcrc.org.

Intel, the world's largest chip maker, is also a leading manufacturer of computer, networking and communications products. Additional information about Intel is available at http://www.intel.com/pressroom.

Intel is a trademark or registered trademark of Intel Corporation or its subsidiaries in the United States and other countries.
* Other names and brands may be claimed as the property of others.





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More on artificial viruses and the creationof designed lifeforms. This goes directly to the issue of nano-bio interfacing as they are now assembling DNA into artificial designer virus that soon will be programable to perform the tasks defined by the genes utilized.

Here it is folks fresh off the presses.

http://news.bbc.co.u...ure/3268259.stm


Thursday, 13 November, 2003, 19:04 GMT
Scientists use DNA to make virus


The naturally occurring virus does not infect people

US scientists have produced a wholly artificial virus using a method they claim could lead to new lifeforms. These synthetic organisms - on the scale of bacteria - could be engineered to produce clean energy or mop up pollution, the researchers say.

It is only the second time a virus has been constructed from scratch in the lab, but the new effort is said to produce substantially quicker results. The work is reported in the Proceedings of the National Academy of Sciences.


First steps

It was conducted at the Institute of Biological Energy Alternatives in Rockville, Maryland, by Dr Craig Venter and colleagues. Dr Venter was the man who led the private effort to decode the human genome.

He told a news conference on Thursday that being able to make a synthetic virus was just the start of an exercise that would lead to completely artificial or engineered bacteria.

"It's an interim step. Now we have the enabling technology to take us to these next exciting frontiers," Dr Venter said.

For now, "this is basic science at the most basic level with lots of unknowns".

But he added: "The ability to construct synthetic genomes may lead to extraordinary advances in our ability to engineer micro-organisms for many vital energy and environmental purposes".

To make the synthetic virus, Dr Venter's team assembled and spliced together segments of DNA.


Code errors

The newly constructed microbe is a replica of the phiX virus, which occurs naturally and infects bacteria - not humans.

PhiX was the first organism to have its genetic code read, in 1978. Its genome consists of 5,386 units - or base pairs - of DNA arranged in a small circle.

We have the enabling technology to take us to these next exciting frontiers
Dr Craig Venter

Other researchers had previously synthesised the poliovirus, which is slightly bigger, employing enzymes usually found in cells. But this effort took years to achieve and produced viruses with defects in their code.

In an effort to improve the speed and accuracy of virus building, Dr Venter and colleagues adapted a frequently used technique in genomic science called the polymerase chain reaction (PCR) which is used to copy DNA segments.

The researchers assembled the phiX genome from oligonucleotides - small pieces of single-stranded DNA - and then combined these into the double stands of the complete genome using their new polymerase cycle assembly (PCA) method. The whole process of building the synthetic phiX took just 14 days.


Works the same

The artificial bacteriophage behaves just like the "natural" one. It has the ability to infect and kill bacterial cells and is indistinguishable from its counterpart.

The scientists say the ability to quickly and accurately synthesise long segments of DNA could help them understand the function of particular genes, and may be a stepping stone to manipulating more complex organisms.

Dr Venter is investigating bacterial organisms to see if they have the potential to meet some of society's energy needs. These microbes might pump out hydrogen to drive electric fuel cells or absorb carbon dioxide to mitigate the effects of global warming.

Scientists envision modifying existing bacteria to improve their performance or constructing artificial bugs to carry out wholly novel tasks.

At the news conference, US Energy Secretary Spencer Abraham called the accomplishment "an extraordinary and exciting development" that will speed up our ability to develop biology-based solutions for some of our most pressing energy and environmental challenges".

"With this advance it is easier to imagine, in the not-too-distant future, a colony of specially designed microbes living within the emission-control system of a coal-fired plant, consuming its pollution and its carbon dioxide, or employing microbes to radically reduce water pollution or to reduce the toxic effects of radioactive waste".

Methuselah enzymes: SEN and the art

Enzymes, the workhorses of chemical reactions in cells, lead short and brutal lives. They cleave and assemble proteins and metabolize compounds for a few hours, and then they are spent. This sad fact of nature has limited the possibilities of harnessing enzymes as catalytic tools outside the cell, in uses that range from biosensing to toxic waste cleanup. To increase the enzyme's longevity and versatility, a team at the Department of Energy's Pacific Northwest National Laboratory in Richland, Wash., has caged single enzymes to create a new class of catalysts called SENs, or single enzyme nanoparticles. The nanostructure protects the catalyst, allowing it to remain active for five months instead of hours.

"The principal concept can be used with many water-soluble enzymes," said Jungbae Kim, PNNL senior scientist who described the feat here today at the national meeting of the American Chemical Society.

"Converting free enzymes into these novel enzyme-containing nanoparticles can result in significantly more stable catalytic activity," added Jay Grate, PNNL laboratory fellow and SENs co-inventor.

Kim and Grate, working in the W.R. Wiley Environmental Molecular Sciences Laboratory at PNNL, modified a common protein-splitting enzyme called alpha-chymotrypsin. They modified the enzyme surface to make it soluble, then added vinyl reagents to induce the growth of molecular threads, or polymers, from the enzyme surface. A second polymerization step cross-linked silicon chains, forming a basketball-netlike structure a few nanometers thick. What result are SENs that appear in electron microscopic images as hollow enzyme-containing nanostructures about 8 nanometers across. Kim and Grate found that by using less reactive forms of vinyl they could vary the thickness of the nano-netting by half. Thick or thin, the porous netting preserves the shape of the enzyme inside yet allows its active site to interact with a substrate. SENs are also amenable to storage; they have been refrigerated for five months, losing little of their activity.

Among the uses Kim noted for SENs is the breakdown toxic waste--a single treatment could last months. Stabilized enzymes are also a prerequisite for many types of biosensors. And they may be of interest for coating surfaces, with application ranging from medicine (protecting implants from protein plaques) to shipping (keeping barnacles off hulls).

While it could be good for some enzymes for others it could just spell out plaques and unwanted activity.

I wasn't sure where to put this, but I hate to start a new topic every time new research is released so here it goes:

Nano-particles could help deliver higher amounts of anti-oxidants through the gut.

This is promising for the delivery of compounds through the gut. Even though this report is discussing the delivery of anti-oxidants, I think it would have better uses with other essential compounds or pharmaceuticals. After I read the title, I was worried that some supplement company would jump on this type of technology in order to "amp up" their multi-vitamin, maybe delivering previously un-heard of and potentially harmful dosages. Then again, if it was used to substantially decrease the amount of antioxidants needed in a multi, there could be a cost savings.

I haven't had the time to read the article yet but I am wondering, what killed them now?
I mean, if you triple or quadruple the life span of an organism part, it is pretty big change.
What is the next step? what caused the death this time?

Can anyone sum it up please? I will try to read it all when I get back.

I hope I'm not committing too dangerous a form of Necromancy with this reply, but I couldn't help it. I am beginning preliminary research regarding C. elegans lifespan using nano-oxide particles. In our neighbor lab, these particles have facilitated 60% increased survival rates in post-ischemic mouse and rat brains. Similar work has been done in C. elegans , including the Rzigalinski work mentioned here as well as Pt-nanoparticle antioxidant properties.

Kim et al. (2008) showed a 20% increase in lifespan and 40% reduction of oxidative stress (from paraquat) in Pt-NP treatments. Much like Mr. Schooler's work and Kim et al., I will also be measuring lipofuscin as a marker for ageing. My work will involve a wildtype strain as well as a super-oxide dismutase (SOD) knockout. SOD is incredibly important in detoxifying super oxide radicals in cells.

My initial results will be in this May and I hope to follow-up here if it garners any interest.

I hope I'm not committing too dangerous a form of Necromancy with this reply, but I couldn't help it. I am beginning preliminary research regarding C. elegans lifespan using nano-oxide particles. In our neighbor lab, these particles have facilitated 60% increased survival rates in post-ischemic mouse and rat brains. Similar work has been done in C. elegans , including the Rzigalinski work mentioned here as well as Pt-nanoparticle antioxidant properties.

Kim et al. (2008) showed a 20% increase in lifespan and 40% reduction of oxidative stress (from paraquat) in Pt-NP treatments. Much like Mr. Schooler's work and Kim et al., I will also be measuring lipofuscin as a marker for ageing. My work will involve a wildtype strain as well as a super-oxide dismutase (SOD) knockout. SOD is incredibly important in detoxifying super oxide radicals in cells.

My initial results will be in this May and I hope to follow-up here if it garners any interest.

Thanks for posting, Joe. This sort of work is interesting to many of us. How much is known about the mechanisms of the lifespan extension seen from nanoparticles of this sort? Please keep up posted as to your results.