TAG: "Nanotechnology"

Technology optimizes cancer therapy with nanomedicine drug combinations


UCLA bioengineers develop platform that offers personalized approach to treatment.

By Brianna Aldrich, UCLA

In greater than 90 percent of cases in which treatment for metastatic cancer fails, the reason is that the cancer is resistant to the drugs being used. To treat drug-resistant tumors, doctors typically use multiple drugs simultaneously, a practice called combination therapy. And one of their greatest challenges is determining which ratio and combination — from the large number of medications available — is best for each individual patient.

Dr. Dean Ho, a professor of oral biology and medicine at the UCLA School of Dentistry, and Dr. Chih-Ming Ho, a professor of mechanical engineering at the UCLA Henry Samueli School of Engineering and Applied Science, have developed a revolutionary approach that brings together traditional drugs and nanotechnology-enhanced medications to create safer and more effective treatments. Their results are published in the peer-reviewed journal ACS Nano.

Chih-Ming Ho, the paper’s co-corresponding author, and his team have developed a powerful new tool to address drug resistance and dosing challenges in cancer patients. The tool, Feedback System Control.II, or FSC.II, considers drug efficacy tests and analyzes the physical traits of cells and other biological systems to create personalized “maps” that show the most effective and safest drug-dose combinations.

Currently, doctors use people’s genetic information to identify the best possible combination therapies, which can make treatment difficult or impossible when the genes in the cancer cells mutate. The new technique does not rely on genetic information, which makes it possible to quickly modify treatments when mutations arise: the drug that no longer functions can be replaced, and FSC.II can immediately recommend a new combination.

“Drug combinations are conventionally designed using dose escalation,” said Dean Ho, a co-corresponding author of the study and the co-director of the Jane and Jerry Weintraub Center for Reconstructive Biotechnology at the School of Dentistry. “Until now, there hasn’t been a systematic way to even know where the optimal drug combination could be found, and the possible drug-dose combinations are nearly infinite. FSC.II circumvents all of these issues and identifies the best treatment strategy.”

The researchers demonstrated that combinations identified by FSC.II could treat multiple lines of breast cancer that had varying levels of drug resistance. They evaluated the commonly used cancer drugs doxorubicin, mitoxantrone, bleomycin and paclitaxel, all of which can be rendered ineffective when cancer cells eject them before they have had a chance to function.

The researchers also studied the use of nanodiamonds to make combination treatments even more effective. Nanodiamonds — byproducts of conventional mining and refining operations — have versatile characteristics that allow drugs to be tightly bound to their surface, making it much harder for cancer cells to eliminate them and allowing toxic drugs to be administered over a longer period of time.

The use of nanodiamonds to treat cancer was pioneered by Dean Ho, a professor of bioengineering and member of the UCLA Jonsson Comprehensive Cancer Center and the California NanoSystems Institute.

“This study has the capacity to turn drug development, nano or non-nano, upside-down,” he said. “Even though FSC.II now enables us to rapidly identify optimized drug combinations, it’s not just about the speed of discovering new combinations. It’s the systematic way that we can control and optimize different therapeutic outcomes to design the most effective medicines possible.”

The study found that FSC.II-optimized drug combinations that used nanodiamonds were safer and more effective than optimized drug-only combinations. Optimized nanodrug combinations also outperformed randomly designed nanodrug combinations.

“This optimized nanodrug combination approach can be used for virtually every type of disease model and is certainly not limited to cancer,” said Chih-Ming Ho, who also holds UCLA’s Ben Rich Lockheed Martin Advanced Aerospace Tech Endowed Chair. “Additionally, this study shows that we can design optimized combinations for virtually every type of drug and any type of nanotherapy.”

Both Dean Ho and Chih-Ming Ho have collaborated with other researchers and have validated FSC.II’s efficacy in many other types of cancers, infectious diseases and other diseases.

Other co-authors were Hann Wang, Dong-Keun Lee, Kai-Yu Chen and Kangyi Zhang, all of UCLA’s department of bioengineering, School of Dentistry, California NanoSystems Institute and Jonsson Cancer Center; Jing-Yao Chen of UCLA’s department of chemical and biomolecular engineering; and Aleidy Silva of UCLA’s department of mechanical and aerospace engineering.

The work was supported in part by the National Cancer Institute, the National Science Foundation, the V Foundation for Cancer Research, the Wallace H. Coulter Foundation, the Society for Laboratory Automation and Screening, and Beckman Coulter Life Sciences.

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Stomach acid-powered micromotors get first test in living animal


Tiny motors may someday offer safer, more efficient way to deliver drugs or diagnose tumors.

By Becky Ham, UC San Diego

Researchers at UC San Diego have shown that a micromotor fueled by stomach acid can take a bubble-powered ride inside a mouse. These tiny motors, each about one-fifth the width of a human hair, may someday offer a safer and more efficient way to deliver drugs or diagnose tumors.

The experiment is the first to show that these micromotors can operate safely in a living animal, said professors Joseph Wang and Liangfang Zhang of the NanoEngineering Department at the UC San Diego Jacobs School of Engineering.

Wang, Zhang and others have experimented with different designs and fuel systems for micromotors that can travel in water, blood and other body fluids in the lab. “But this is the first example of loading and releasing a cargo in vivo,” said Wang. “We thought it was the logical extension of the work we have done, to see if these motors might be able to swim in stomach acid.”

Stomach acid reacts with the zinc body of the motors to generate a stream of hydrogen microbubbles that propel the motors forward. In their study published in the journal ACS Nano, the researchers report that the motors lodged themselves firmly in the stomach lining of mice. As the zinc motors are dissolved by the acid, they disappear within a few days leaving no toxic chemical traces.

“This initial work verifies that this motor can function in a real animal and is safe to use,” said Zhang.

In the experiment, the mice ingested tiny drops of solution containing hundreds of the micromotors. The motors become active as soon as they hit the stomach acid and zoom toward the stomach lining at a speed of 60 micrometers per second. They can self-propel like this for up to 10 minutes.

This propulsive burst improved how well the cone-shaped motors were able to penetrate and stick in the mucous layer covering the stomach wall, explained Zhang. “It’s the motor that can punch into this viscous layer and stay there, which is an advantage over more passive delivery systems,” he said.

The researchers found that nearly four times as many zinc micromotors found their way into the stomach lining compared with platinum-based micromotors, which don’t react with and can’t be fueled by stomach acid.

Wang said it may be possible to add navigation capabilities and other functions to the motors, to increase their targeting potential. Now that his team has demonstrated that the motors work in living animals, he noted, similar nanomachines soon may find a variety of applications including drug delivery, diagnostics, nanosurgery and biopsies of hard-to-reach tumors.

Wang and Zhang were joined on the study by UC San Diego nanoengineers Wei Gao, Renfeng Dong, Soracha Thamphiwatana, Jinxing Li and Weiwei Gao.

The publication is “Artificial Micromotors in the Mouse’s Stomach: A Step toward in Vivo Use of Synthetic Motors,” published online Dec. 30 in the journal ACS Nano.

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Temporary tattoo offers needle-free way to monitor glucose


‘Proof-of-concept’ tattoo could pave way for UC San Diego to explore others uses of device.

Nanoengineers at UC San Diego have tested a temporary tattoo that both extracts and measures the level of glucose in the fluid in between skin cells.

By Ioana Patringenaru

Nanoengineers at UC San Diego have tested a temporary tattoo that both extracts and measures the level of glucose in the fluid in between skin cells. This first-ever example of the flexible, easy-to-wear device could be a promising step forward in noninvasive glucose testing for patients with diabetes.

The sensor was developed and tested by graduate student Amay Bandodkar and colleagues in professor Joseph Wang’s laboratory at the NanoEngineering Department and the Center for Wearable Sensors at the Jacobs School of Engineering at UC San Diego. Bandodkar said this “proof-of-concept” tattoo could pave the way for the center to explore other uses of the device, such as detecting other important metabolites in the body or delivering medicines through the skin.

At the moment, the tattoo doesn’t provide the kind of numerical readout that a patient would need to monitor his or her own glucose. But this type of readout is being developed by electrical and computer engineering researchers in the Center for Wearable Sensors. “The readout instrument will also eventually have Bluetooth capabilities to send this information directly to the patient’s doctor in real-time or store data in the cloud,” said Bandodkar.

The research team is also working on ways to make the tattoo last longer while keeping its overall cost down, he noted. “Presently the tattoo sensor can easily survive for a day. These are extremely inexpensive — a few cents — and hence can be replaced without much financial burden on the patient.”

The center “envisions using these glucose tattoo sensors to continuously monitor glucose levels of large populations as a function of their dietary habits,” Bandodkar said. Data from this wider population could help researchers learn more about the causes and potential prevention of diabetes, which affects hundreds of millions of people and is one of the leading causes of death and disability worldwide.

People with diabetes often must test their glucose levels multiple times per day, using devices that use a tiny needle to extract a small blood sample from a fingertip. Patients who avoid this testing because they find it unpleasant or difficult to perform are at a higher risk for poor health, so researchers have been searching for less invasive ways to monitor glucose.

In their report in the journal Analytical Chemistry, Wang and his co-workers describe their flexible device, which consists of carefully patterned electrodes printed on temporary tattoo paper. A very mild electrical current applied to the skin for 10 minutes forces sodium ions in the fluid between skin cells to migrate toward the tattoo’s electrodes. These ions carry glucose molecules that are also found in the fluid. A sensor built into the tattoo then measures the strength of the electrical charge produced by the glucose to determine a person’s overall glucose levels.

“The concentration of glucose extracted by the non-invasive tattoo device is almost hundred times lower than the corresponding level in the human blood,” Bandodkar explained. “Thus we had to develop a highly sensitive glucose sensor that could detect such low levels of glucose with high selectivity.”

A similar device called GlucoWatch from Cygnus Inc. was marketed in 2002, but the device was discontinued because it caused skin irritation, the UC San Diego researchers note. Their proof-of-concept tattoo sensor avoids this irritation by using a lower electrical current to extract the glucose.

Wang and colleagues applied the tattoo to seven men and women between the ages of 20 and 40 with no history of diabetes. None of the volunteers reported feeling discomfort during the tattoo test, and only a few people reported feeling a mild tingling in the first 10 seconds of the test.

To test how well the tattoo picked up the spike in glucose levels after a meal, the volunteers ate a carb-rich meal of a sandwich and soda in the lab. The device performed just as well at detecting this glucose spike as a traditional finger-stick monitor.

The researchers say the device could be used to measure other important chemicals such as lactate, a metabolite analyzed in athletes to monitor their fitness. The tattoo might also someday be used to test how well a medication is working by monitoring certain protein products in the intercellular fluid, or to detect alcohol or illegal drug consumption.

Bandodkar was joined on the study by UC San Diego nanoengineers Wenzhao Jia, Ceren Yardımcı, Xuan Wang, Julian Ramirez and Wang, director of the Center for Wearable Sensors and SAIC Endowed Chair and distinguished professor in the NanoEngineering Department.

The publication is “Tattoo-Based Noninvasive Glucose Monitoring: A Proof-of-Concept Study,” published Dec. 12 in the journal Analytical Chemistry.

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‘NanoVelcro,’ temperature control used to extract tumor cells from blood


System could allow doctors to detect, analyze cancer to tailor treatment for individuals.

The device, developed at UCLA, enables scientists to control the blood’s temperature — the way coffeehouses would with an espresso machine — to capture and release the cancer cells in optimal conditions. (Credit: Tseng Lab, UCLA)

By Shaun Mason, UCLA

An international group led by scientists at UCLA’s California NanoSystems Institute has developed a new method for effectively extracting and analyzing cancer cells circulating in patients’ blood.

Circulating tumor cells are cancer cells that break away from tumors and travel in the blood, looking for places in the body to start growing new tumors called metastases. Capturing these rare cells would allow doctors to detect and analyze the cancer so they could tailor treatment for individual patients.

In his laboratory at the UCLA California NanoSystems Institute, Hsian-Rong Tseng, a professor of molecular and medical pharmacology, used a device he invented to capture circulating tumor cells from blood samples.

The device, called the NanoVelcro Chip, is a postage-stamp–sized chip with nanowires that are 1,000 times thinner than a human hair and are coated with antibodies that recognize circulating tumor cells. When 2 milliliters of blood are run through the chip, the tumor cells stick to the nanowires like Velcro.

Capturing the tumor cells was just part of the battle, though. To analyze them, Tseng’s team needed to be able to separate the cells from the chip without damaging them.

In earlier experiments with NanoVelcro, the scientists used a technique called laser capture microdissection that was effective in removing individual cells from the chip without damaging them, but the method was time-consuming and labor intensive, and it required highly specialized equipment.

Now Tseng and his colleagues have developed a thermoresponsive NanoVelcro purification system, which enables them to raise and lower the temperature of the blood sample to capture (at 37 degrees Celsius) and release (at 4 degrees Celsius) circulating tumor cells at their optimal purity. Polymer brushes on the NanoVelcro’s nanowires respond to the temperature changes by altering their physical properties, allowing them to capture or release the cells.

Because it could make extracting the cancer cells much more efficient and cost-effective at a time in a patient’s life when information is needed as quickly as possible, Tseng said it is conceivable that the new system will replace laser capture microdissection as the standard protocol.

“With our new system, we can control the blood’s temperature — the way coffeehouses would with an espresso machine — to capture and then release the cancer cells in great purity, ” said Tseng, who is also a member of UCLA’s Jonsson Comprehensive Cancer Center. “We combined the thermoresponsive system with downstream mutational analysis to successfully monitor the disease evolution of a lung cancer patient. This shows the translational value of our device in managing non–small-cell lung cancer with underlying mutations.”

The study, which was published online by the journal ACS Nano, brought together an interdisciplinary team from the U.S., China, Taiwan and Japan. The research was supported by the National Institutes of Health, RIKEN (Japan), Academia Sinica (Taiwan), Sun Yat-sen University (China) and the National Natural Science Foundation of China.

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New therapy holds promise for restoring vision


It has several advantages over other sight restoration therapies now under investigation.

Benjamin Gaub and John Flannery observing a mouse in a water maze, in which the mouse swims to a platform designated by bright flashing lights. (Photo by Mervi Kuronen)

By Robert Sanders, UC Berkeley

A new genetic therapy not only helped blind mice regain enough light sensitivity to distinguish flashing from non-flashing lights, but also restored light response to the retinas of dogs, setting the stage for future clinical trials of the therapy in humans.

The therapy employs a virus to insert a gene for a common ion channel into normally blind cells of the retina that survive after the light-responsive rod and cone photoreceptor cells die as a result of diseases such as retinitis pigmentosa. Photoswitches – chemicals that change shape when hit with light – are then attached to the ion channels to make them open in response to light, activating the retinal cells and restoring light sensitivity.

Afflicting people of all ages, retinitis pigmentosa causes a gradual loss of vision, akin to losing pixels in a digital camera. Sight is lost from the periphery to the center, usually leaving people with the inability to navigate their surroundings. Some 100,000 Americans suffer from this group of inherited retinal diseases.

In a paper appearing online this week in the early edition of the journal Proceedings of the National Academy of Sciences, University of California, Berkeley, scientists who invented the photoswitch therapy and vision researchers at the School of Veterinary Medicine of the University of Pennsylvania (PennVet) report that blind mice regained the ability to navigate a water maze as well as normal mice.

The treatment worked equally well to restore light responses to the degenerated retinas of mice and dogs, indicating that it may be feasible to restore some light sensitivity in blind humans.

“The dog has a retina very similar to ours, much more so than mice, so when you want to bring a visual therapy to the clinic, you want to first show that it works in a large animal model of the disease,” said lead researcher Ehud Isacoff, professor of molecular and cell biology at UC Berkeley. “We’ve now showed that we can deliver the photoswitch and restore light response to the blind retina in the dog as well as in the mouse, and that the treatment has the same sensitivity and speed of response. We can reanimate the dog retina.”

The therapy has several advantages over other sight restoration therapies now under investigation, says vision scientist John Flannery, UC Berkeley professor of vision science and of molecular and cell biology. It uses a virus already approved by the Food and Drug Administration for other genetic therapies in the eye; it delivers an ion channel gene similar to one normally found in humans, unlike others that employ genes from other species; and it can easily be reversed or adjusted by supplying new chemical photoswitches. Dogs with the retinal degeneration provide a key test of the new therapy.

“Our ability to test vision is very, very limited in mice because, even in the healthy state, they are not very visual animals, their behaviors are largely driven by their other senses,” he says. “Dogs have a very sophisticated visual system, and are being used already for testing ophthalmic gene therapy.”

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Vegetable oil ingredient is key to destroying gastric disease bacteria


Therapeutic nanoparticle that contains linolenic acid shows promise.

Liangfang Zhang, UC San Diego

By Heather Buschman, UC San Diego

The bacterium Helicobacter pylori is strongly associated with gastric ulcers and cancer. To combat the infection, researchers at the UC San Diego School of Medicine and Jacobs School of Engineering developed LipoLLA, a therapeutic nanoparticle that contains linolenic acid, a component in vegetable oils. In mice, LipoLLA was safe and more effective against H. pylori infection than standard antibiotic treatments.

The results are published online Nov. 24 in the Proceedings of the National Academy of Sciences.

“Current H. pylori treatments are facing a major challenge — antibiotic resistance,” said Liangfang Zhang, Ph.D., professor in the UC San Diego Moores Cancer Center and Department of Nanoengineering. “Our goal was to develop a nanotherapeutic that can tolerate the harsh gastric environment, kill H. pylori and avoid resistance.” Zhang and Marygorret Obonyo, Ph.D., assistant professor in the Moores Cancer Center and Department of Medicine, are co-senior authors of the study.

LipoLLA is a lipid (fat) particle that contains linolenic acid. When LipoLLA encounters H. pylori, it fuses with the bacterial membrane. Then the particle’s linolenic acid payload spills out, disrupting the membrane and killing the bacteria.

Zhang, Obonyo and their team labeled LipoLLA particles with fluorescent markers, fed them to mice and watched as the particles distributed themselves in the stomach lining — and stayed there. After treatment, they measured bacterial load in the stomach and markers of inflammation. Compared to standard antibiotic therapies, LipoLLA was more effective at getting rid of H. pylori. What’s more, LipoLLA was not toxic to the mice and the bacteria did not develop resistance to the therapy.

“This is the first step to verify that we can make this therapeutic nanoparticle and demonstrate that it works to reduce H. pylori colonization. We’re now working to further enhance the particle, making it more stable and more effective,” Zhang said.

Co-authors include Soracha Thamphiwatana and Weiwei Gao, UC San Diego.

This research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK095168), part of the National Institutes of Health.

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Biochemists build largest synthetic molecular ‘cage’ ever


New nanoscale protein container could lead to synthetic vaccines.

Todd Yeates and Yen-Ting Lai, UCLA

UCLA biochemists have created the largest-ever protein that self-assembles into a molecular “cage.” The research could lead to synthetic vaccines that protect people from the flu, HIV and other diseases.

At a size hundreds of times smaller than a human cell, it also could lead to new methods of delivering pharmaceuticals inside of cells, or to the creation of new nanoscale materials.

The protein assembly, which is shaped like a cube, was constructed from 24 copies of a protein designed in the laboratory of Todd Yeates, a UCLA professor of chemistry and biochemistry. It is porous — more so than any other protein assembly ever created — with large openings that would enable other large protein molecules to enter and exit.

The research was recently published online in the journal Nature Chemistry and will appear in a future print edition.

Yeates, the study’s senior author, has sought to build complex protein structures that self-assemble since he first published research on self-assembling proteins in 2001. In 2012, he and colleagues produced a self-assembling molecular cage made from 12 protein pieces combined perfectly like pieces of a puzzle. Now they have done so with 24 pieces, and they are currently attempting to design a molecular cage with 60 pieces. Building each larger protein presented new scientific challenges, but the bigger sizes could potentially carry more “cargo.”

In principle, these molecular structures should be able to carry cargo that could then be released inside of cells, said Yeates, who is a member of the UCLA–Department of Energy Institute of Genomics and Proteomics and the California NanoSystems Institute at UCLA.

Yeates’ research was funded by the National Science Foundation and the UCLA–DOE Institute of Genomics and Proteomics. The lead author was Yen-Ting Lai, who conducted the research as a UCLA graduate student in Yeates’ laboratory and is now a postdoctoral scholar at Arizona State University.

The molecular cube is probably too porous to serve as a container — for medicine, for example — inside a human body. “But the design principles for making a cage that is more closed would be the same,” Yeates said, adding that there are ways to make the cage less stable when it gets into a cell, so that it would release its cargo, such as a toxin that could kill a cancer cell.

Yeates said that his lab’s method also could lead to the production of synthetic vaccines that would mimic what a cell sees when it’s infected by a virus. The vaccines would provoke a strong response from the body’s immune system and perhaps provide better protection from diseases than traditional vaccines.

Yeates has started a research collaboration with Peter Kwong, chief of the structural biology section at the National Institutes of Health and a national leader in the structural biology of disease viruses. They will conduct research on attaching viral antigens to molecular cages.

Other co-authors of the Nature Chemistry research were Carol Robinson, Eamonn Reading and Arthur Laganowsky of the University of Oxford; Francisco Asturias and Kuang-Lei Tsai of the Scripps Research Institute; and John Tainer and Greg Hura of the Lawrence Berkeley National Laboratory.

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Bio-inspired bleeding control


Researchers synthesize platelet-like nanoparticles that can do more than clot blood.

The researchers (from left): Aaron Anselmo, Samir Mitragotri, Stefano Menegatti and Sunny Kumar. Not pictured: Douglas Vogus and Todd Squires. (Photo by Sonia Fernandez)

By Sonia Fernandez, UC Santa Barbara

Stanching the free flow of blood from an injury remains a holy grail of clinical medicine. Controlling blood flow is a primary concern and first line of defense for patients and medical staff in many situations, from traumatic injury to illness to surgery. If control is not established within the first few minutes of a hemorrhage, further treatment and healing are impossible.

At UC Santa Barbara, researchers in the Department of Chemical Engineering and at Center for Bioengineering (CBE) have turned to the human body’s own mechanisms for inspiration in dealing with the necessary and complicated process of coagulation. By creating nanoparticles that mimic the shape, flexibility and surface biology of the body’s own platelets, they are able to accelerate natural healing processes while opening the door to therapies and treatments that can be customized to specific patient needs.

“This is a significant milestone in the development of synthetic platelets, as well as in targeted drug delivery,” said Samir Mitragotri, CBE director, who specializes in targeted therapy technologies. Results of the researchers’ findings appear in the current issue of the journal ACS Nano.
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Research on cell biology mystery may reveal root causes of Alzheimer’s


A well-known cellular structure orchestrates how vault nanoparticles naturally form in cells.

In the 1980s, professor Leonard Rome and his then-postdoctoral fellow Nancy Kedersha made a breakthrough in cell biology when they discovered vaults, naturally occurring nanoparticles — of a size measured in nanometers (1 nanometer = 1 billionth of a meter) — that are composed mostly of proteins and number in the thousands inside every cell of the body.

In the decades since, Rome’s team has discovered how to form vaults in the laboratory using the proteins they consist of. While naturally occurring vaults contain other elements, Rome’s team built empty ones, which eventually enabled them to pursue the idea of inserting drug molecules into vaults. Those could then be put in serum, injected into patients, and directed to specific cells where they release the drugs. Thus, vaults are being developed as a highly accurate drug-delivery system that is being commercialized.

But one question that Rome and his team couldn’t answer was how the natural vaults originally formed inside cells. Now Rome and his collaborators at UCLA’s California NanoSystems Institute appear to have solved that mystery.

In a study published online today (Oct. 30) in the journal ACS Nano, Rome’s team, led by first author and postdoctoral scholar Jan Mrazek, report data that suggests that polyribosomes — small molecular machines that read genetic information and form proteins inside cells — work like 3-D printers to both create and link together proteins and correctly form them into vaults. (Watch a brief animated explanation of how it works.)

“This idea needs some further research and confirmation, but it is a very elegant model and we are convinced that it explains how vaults are formed,” said Rome, who is associate director of the California NanoSystems Institute. “If the model is correct, it reveals something new about cell biology — that this polyribosome that has been known for 50 years has a heretofore unknown function. Namely, it orchestrates the assembly of macromolecular complexes such as vaults, and other structures in a cell that are made of multiple proteins.”

Mrazek said that this possible function of polyribosomes may also provide new understanding of protein aggregation, which is a clumping of deformed proteins that happens in such diseases as Alzheimer’s, Parkinson’s and Lou Gehrig’s.

“If a protein is not made correctly, it’s possible that these deformities can alter the guided assembly of macromolecules by the polyribosomes,” Mrazek said. “Once you understand that there is a machine in the cell that directs the formation of these macromolecular complexes, you can see where things might go wrong with that machine. By studying nanotechnology we have revealed something unknown about basic cell biology that might have wider implications.”

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Biosensor technology could allow rapid detection of Ebola virus


Rapid detection of viruses among potential applications of research at UC Santa Cruz.

Ali Yanik, UC Santa Cruz

In 2010, Ahmet Ali Yanik published his first paper on the rapid detection of Ebola virus using new biosensor technology he and colleagues at Boston University had invented. But he found there was little interest at the time in developing the technology further.

“People told me that there wasn’t any profit in it because this disease only affects people in the developing world,” Yanik said.

Now, however, Ebola hemorrhagic fever has captured the attention of first world countries in a big way. The current outbreak in West Africa began spreading out of control just as Yanik was setting up his lab as a new faculty member at UC Santa Cruz, where he is an assistant professor of electrical engineering. Yanik plans to resume his work on virus detection in addition to ongoing projects involving biosensors for other biomedical applications. The current Ebola crisis may subside before his technology can be perfected, since there are still many challenges to overcome, but the need will remain for simple and inexpensive virus detection techniques, he said.

“The truth is that Lassa virus, which is related to Ebola and also causes hemorrhagic fever, infects nearly half a million people every year in Africa and kills more people than Ebola, but it doesn’t make the news. So there has been an ongoing crisis with hemorrhagic fever viruses, and now it’s finally getting some serious attention,” Yanik said.

His goal is to create a low-cost biosensor that can be used to detect specific viruses without the need for skilled operators or expensive equipment. “We need a platform for virus detection that is like the pregnancy tests you can use at home,” Yanik said. “The initial symptoms of hemorrhagic fever are similar to the flu, and you just cannot treat every person with flu symptoms as a potential Ebola-infected patient. It needs to be simple and cheap.”

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Engineers develop prototype of low-cost, disposable lung infection detector


NSF grant supports UC Irvine’s efforts to improve manufacturing process for nanodevices.

Imagine a low-cost, disposable breath analysis device that a person with cystic fibrosis could use at home along with a smartphone to immediately detect a lung infection, much like the device police use to gauge a driver’s blood alcohol level.

Timely knowledge of a lung infection would let people with CF or other inflammatory respiratory conditions seek immediate treatment and thereby prevent life-shortening permanent damage to their already vulnerable airways.

Thanks to a nearly $1.3 million grant from the National Science Foundation, UC Irvine engineers can continue developing this type of nanotechnology device – and potentially many others – using a more wide-scale manufacturing process.

Materials scientist Regina Ragan and electrical engineer Filippo Capolino have created a nano-optical sensor that can detect trace levels of infection in a small sample of breath. They made the sensor in the laboratory but would like to see it become commercially available. In addition to diagnosing medical conditions, the device could be modified to monitor environmental conditions – for instance, identifying harmful airborne agents produced through automotive or chemical industry practices.

Nanotechnologies such as this sensor depend on extremely small, nanometer-scale building blocks. A nanometer is about 100,000 times smaller than the width of a human hair. Fabricating on this tiny scale poses huge challenges, since most of the current methods that achieve a high level of precision are too costly and slow to be viable for manufacturing.

“With support from the NSF and input from industry, our goal is to help nanoscale manufacturing processes leave the laboratory – where they’ve been confined – and become usable in widespread commercial applications,” said Ragan, associate professor of chemical engineering & materials science and principal investigator on the project.

This grant highlights the strength of our faculty in both nanosciences and advanced manufacturing,” said Gregory Washington, dean of The Henry Samueli School of Engineering. “The Samueli School is poised to move forward as a force in this area.”

Co-principal investigators are Capolino, associate professor of electrical engineering & computer science; Ozdal Boyraz, associate professor of electrical engineering & computer science; and Marc Madou, Chancellor’s Professor of mechanical & aerospace engineering.

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Scientists engineer antibiotics to catch up in race against drug resistance


Souped-up antibiotics attack cells responsible for making bacteria resistant to new drugs.

We face an urgent global health problem because scientists are not developing new antibiotics as fast as bacteria are developing antibiotic resistance.

But new research from UCLA has made important progress toward solving this problem. An interdisciplinary team of scientists from UCLA’s California NanoSystems Institute has developed a method to re-engineer antibiotics that sharply enhances their activity against certain key bacterial cells, called persisters, that are responsible for making bacteria resistant to new drugs.

Persister cells slow down their metabolism and shut down their mechanisms for taking in molecules, preventing normal antibiotics from getting into them, which is necessary for the drug to kill the bug. After the persister cells survive the initial antibiotic treatment, they pass on their genes as the bacteria reproduce.

Led by Gerard Wong, professor in the UCLA Department of Chemistry and Biochemistry and the Department of Bioengineering, and Andrea Kasko, associate professor of bioengineering, the team has developed a method analogous to taking an ordinary car and adding high-performance parts to make a fast and furious street racer.

“We’re in an unsustainable race with bacteria. They become resistant to our antimicrobials too fast,” Wong said. “It takes upwards of $100 million to develop one antibiotic drug, and bacteria develop resistance to it within two years. It’s a race that we can’t win. This reality brought us to the idea of taking an existing antibiotic and renovating it, giving it a new, complementary antimicrobial ability while preserving its original ability to make a better drug overall.”

The study was published Aug. 18 online in the journal ACS Nano.

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