Cellular and Developmental Biology

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Cellular and Developmental Biology

Anderson, United States
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News Article | April 25, 2017
Site: www.prnewswire.com

"I am excited for this opportunity and look forward to working with the i2 team as we seek to optimize the value of the Company's unique and proprietary suite of transformative technologies and assets.  The breadth of i2's cutting edge discovery technologies allows me to utilize my antibody experience as well as the chance to forge new collaborations outside this space as well," Mr. Kubik added. Mark has extensive experience in the biopharmaceutical industry as a business development executive in roles of increasing impact in bioscience and drug discovery and development.  He has led negotiation of transformative and award-winning technology and product partnerships for leading therapeutics companies including global co-development agreements on behalf of Abgenix (now Amgen) with Immunex for Vectibix® (panitumab), on behalf of Seattle Genetics with Takeda for Adcetris® (brentuximab vedotin) and on behalf of MacroGenics with Gilead.  Mark graduated cum laude from the University of Colorado-Boulder (CU) in Molecular, Cellular and Developmental Biology (MCDB) and also holds an MBA in Finance from CU. About i2 Pharmaceuticals i2 Pharmaceuticals is a biopharmaceutical company focused on next generation discovery and development of  therapeutics with a focus on personalized cancer treatment.  i2 is unique in that it generates its pipeline of product candidates from its proprietary suite of transformative technologies including small molecules, antibodies and nucleic acid based therapeutics.  We are innovators coupling the power of cutting edge discovery technologies with ground breaking diagnostics to accelerate the development of more effective, safer therapeutics.  For more information please visit http://www.i2pharma.com. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/i2-pharmaceuticals-appoints-chief-business-officer-300445633.html


Nothing beats nature. The diverse and wonderful varieties of cells and tissues that comprise the human body are evidence of that. Each one of us starts out as a mass of identical, undifferentiated cells, and thanks to a combination of signals and forces, each cell responds by choosing a developmental pathway and multiplying into the tissues that become our hearts, brains, hair, bones or blood. A major promise of studying human embryonic stem cells is to understand these processes and apply the knowledge toward tissue engineering. Researchers in UC Santa Barbara's departments of Chemistry and Biochemistry, and of Molecular, Cellular and Developmental Biology have gotten a step closer to unlocking the secrets of tissue morphology with a method of three-dimensional culturing of embryonic stem cells using light. "The important development with our method is that we have good spatiotemporal control over which cell -- or even part of a cell -- is being excited to differentiate along a particular gene pathway," said lead author Xiao Huang, who conducted this study as a doctoral student at UCSB and is now a postdoctoral scholar in the Desai Lab at UC San Francisco. The research, titled "Light-Patterned RNA Interference of 3D-Cultured Human Embryonic Stem Cells," appears in volume 28, issue 48 of the journal Advanced Materials. Similar to other work in the field of optogenetics -- which largely focuses neurological disorders and activity in living organisms, leading to insights into diseases and conditions such as Parkinson's and drug addiction -- this new method relies on light to control gene expression. The researchers used a combination of hollow gold nanoshells attached to small molecules of synthetic RNA (siRNA) -- a molecule that plays a large role in gene regulation -- and thermoreversible hydrogel as 3D scaffolding for the stem cell culture, as well as invisible, near-infrared (NIR) light. NIR light, Huang explained, is ideal when creating a three-dimensional culture in the lab. "Near-infrared light has better tissue penetration that is useful when the sample becomes thick," he explained. In addition to enhanced penetration -- up to 10 cm deep -- the light can be focused tightly to specific areas. Irradiation with the light released the RNA molecules from the nanoshells in the sample and initiated gene-silencing activity, which knocked down green fluorescent protein genes in the cell cluster. The experiment also showed that the irradiated cells grew at the same rate as the untreated control sample; the treated cells showed unchanged viability after irradiation. Of course, culturing tissues consisting of related but varying cell types is a far more complex process than knocking down a single gene. "It's a concert of orchestrated processes," said co-author and graduate student researcher Demosthenes Morales, describing the process by which human embryonic stem cells become specific tissues and organs. "Things are being turned on and turned off." Perturbing one aspect of the system, he explained, sets off a series of actions along the cells' developmental pathways, much of which is still unknown. "One reason we're very interested in spatiotemporal control is because these cells, when they're growing and developing, don't always communicate the same way," Morales said, explaining that the resulting processes occur at different speeds, and occasionally overlap. "So being able to control that communication on which cell differentiates into which cell type will help us to be able to control tissue formation," he added. The fine control over cell development provided by this method also allows for the three-dimensional culture of tissues and organs from embryonic stem cells for a variety of applications. Engineered tissues can be used for therapeutic purposes, including replacements for organs and tissues that have been destroyed due to injury or disease. They can be used to give insight into the body's response to toxins and therapeutic agents.


News Article | May 15, 2017
Site: www.eurekalert.org

UCSB researchers develop a more precise and cUCSB researchers develop a more precise and controlled method of engineering tissues from stem cellsontrolled method of engineering tissues from stem cells Nothing beats nature. The diverse and wonderful varieties of cells and tissues that comprise the human body are evidence of that. Each one of us starts out as a mass of identical, undifferentiated cells, and thanks to a combination of signals and forces, each cell responds by choosing a developmental pathway and multiplying into the tissues that become our hearts, brains, hair, bones or blood. A major promise of studying human embryonic stem cells is to understand these processes and apply the knowledge toward tissue engineering. Researchers in UC Santa Barbara's departments of Chemistry and Biochemistry, and of Molecular, Cellular and Developmental Biology have gotten a step closer to unlocking the secrets of tissue morphology with a method of three-dimensional culturing of embryonic stem cells using light. "The important development with our method is that we have good spatiotemporal control over which cell -- or even part of a cell -- is being excited to differentiate along a particular gene pathway," said lead author Xiao Huang, who conducted this study as a doctoral student at UCSB and is now a postdoctoral scholar in the Desai Lab at UC San Francisco. The research, titled "Light-Patterned RNA Interference of 3D-Cultured Human Embryonic Stem Cells," appears in volume 28, issue 48 of the journal Advanced Materials. Similar to other work in the field of optogenetics -- which largely focuses neurological disorders and activity in living organisms, leading to insights into diseases and conditions such as Parkinson's and drug addiction -- this new method relies on light to control gene expression. The researchers used a combination of hollow gold nanoshells attached to small molecules of synthetic RNA (siRNA) -- a molecule that plays a large role in gene regulation -- and thermoreversible hydrogel as 3D scaffolding for the stem cell culture, as well as invisible, near-infrared (NIR) light. NIR light, Huang explained, is ideal when creating a three-dimensional culture in the lab. "Near-infrared light has better tissue penetration that is useful when the sample becomes thick," he explained. In addition to enhanced penetration -- up to 10 cm deep -- the light can be focused tightly to specific areas. Irradiation with the light released the RNA molecules from the nanoshells in the sample and initiated gene-silencing activity, which knocked down green fluorescent protein genes in the cell cluster. The experiment also showed that the irradiated cells grew at the same rate as the untreated control sample; the treated cells showed unchanged viability after irradiation. Of course, culturing tissues consisting of related but varying cell types is a far more complex process than knocking down a single gene. "It's a concert of orchestrated processes," said co-author and graduate student researcher Demosthenes Morales, describing the process by which human embryonic stem cells become specific tissues and organs. "Things are being turned on and turned off." Perturbing one aspect of the system, he explained, sets off a series of actions along the cells' developmental pathways, much of which is still unknown. "One reason we're very interested in spatiotemporal control is because these cells, when they're growing and developing, don't always communicate the same way," Morales said, explaining that the resulting processes occur at different speeds, and occasionally overlap. "So being able to control that communication on which cell differentiates into which cell type will help us to be able to control tissue formation," he added. The fine control over cell development provided by this method also allows for the three-dimensional culture of tissues and organs from embryonic stem cells for a variety of applications. Engineered tissues can be used for therapeutic purposes, including replacements for organs and tissues that have been destroyed due to injury or disease. They can be used to give insight into the body's response to toxins and therapeutic agents. Research on this study was also conducted also by Qirui Hu, a postdoctoral fellow in Dennis Clegg's lab at UCSB's Center for Stem Cell Biology and Engineering in the Department of Molecular, Cellular and Developmental Biology, and Yifan Lai in the lab of Norbert Reich in the Department of Chemistry and Biochemistry.


Each one of us starts out as a mass of identical, undifferentiated cells, and thanks to a combination of signals and forces, each cell responds by choosing a developmental pathway and multiplying into the tissues that become our hearts, brains, hair, bones or blood. A major promise of studying human embryonic stem cells is to understand these processes and apply the knowledge toward tissue engineering. Researchers in UC Santa Barbara's departments of Chemistry and Biochemistry, and of Molecular, Cellular and Developmental Biology have gotten a step closer to unlocking the secrets of tissue morphology with a method of three-dimensional culturing of embryonic stem cells using light. "The important development with our method is that we have good spatiotemporal control over which cell—or even part of a cell—is being excited to differentiate along a particular gene pathway," said lead author Xiao Huang, who conducted this study as a doctoral student at UCSB and is now a postdoctoral scholar in the Desai Lab at UC San Francisco. The research, titled "Light-Patterned RNA Interference of 3D-Cultured Human Embryonic Stem Cells," appears in volume 28, issue 48 of the journal Advanced Materials. Similar to other work in the field of optogenetics—which largely focuses neurological disorders and activity in living organisms, leading to insights into diseases and conditions such as Parkinson's and drug addiction—this new method relies on light to control gene expression. The researchers used a combination of hollow gold nanoshells attached to small molecules of synthetic RNA (siRNA)—a molecule that plays a large role in gene regulation—and thermoreversible hydrogel as 3D scaffolding for the stem cell culture, as well as invisible, near-infrared (NIR) light. NIR light, Huang explained, is ideal when creating a three-dimensional culture in the lab. "Near-infrared light has better tissue penetration that is useful when the sample becomes thick," he explained. In addition to enhanced penetration—up to 10 cm deep—the light can be focused tightly to specific areas. Irradiation with the light released the RNA molecules from the nanoshells in the sample and initiated gene-silencing activity, which knocked down green fluorescent protein genes in the cell cluster. The experiment also showed that the irradiated cells grew at the same rate as the untreated control sample; the treated cells showed unchanged viability after irradiation. Of course, culturing tissues consisting of related but varying cell types is a far more complex process than knocking down a single gene. "It's a concert of orchestrated processes," said co-author and graduate student researcher Demosthenes Morales, describing the process by which human embryonic stem cells become specific tissues and organs. "Things are being turned on and turned off." Perturbing one aspect of the system, he explained, sets off a series of actions along the cells' developmental pathways, much of which is still unknown. "One reason we're very interested in spatiotemporal control is because these cells, when they're growing and developing, don't always communicate the same way," Morales said, explaining that the resulting processes occur at different speeds, and occasionally overlap. "So being able to control that communication on which cell differentiates into which cell type will help us to be able to control tissue formation," he added. The fine control over cell development provided by this method also allows for the three-dimensional culture of tissues and organs from embryonic stem cells for a variety of applications. Engineered tissues can be used for therapeutic purposes, including replacements for organs and tissues that have been destroyed due to injury or disease. They can be used to give insight into the body's response to toxins and therapeutic agents. Explore further: Scientists expand ability of stem cells to regrow any tissue type


News Article | May 10, 2017
Site: phys.org

"Rh7 is the first example of a rhodopsin that is important in setting circadian rhythms by being expressed in the central brain, rather than the eye," said Craig Montell, Ph.D., Duggan Professor of Molecular, Cellular and Developmental Biology at the University of California Santa Barbara and senior author of the study. This newly discovered role for Rh7 could have clinical implications down the road. "Identifying new roles for light-sensitive opsins is essential for understanding degenerative retinal disorders and developing potential new treatments," said Lisa Neuhold, Ph.D., program director at the National Eye Institute. Rhodopsins, discovered in the 1870s, are well-known for their important role in light-sensing and image formation. The six previously known fly rhodopsins account for the full function of photoreceptor cells in the fly's eyes, so although the fruit fly genome contained the sequence of a seventh rhodopsin, the role of Rh7 was unclear. To investigate the role of Rh7, Montell and collaborators at the University of California, Irvine, first confirmed that Rh7 sensed light by doing genetic experiments that replaced Rh1, the primary light-sensor in photoreceptor cells of the fly eye, with Rh7. The researchers found that Rh7 could functionally substitute for Rh1 in flies missing Rh1, as measured by electroretinogram, which is an extracellular recording of a neural signal in the fly eye in response to light. Next, the researchers used antibodies recognizing Rh7 to determine its expression pattern. They found that it was expressed in the brain's central pacemaker neurons, which play a role in regulating circadian rhythms. Montell and his team reared fruit flies under a 12-hour light/12-hour dark cycle, then extended one light cycle to 20 hours and measured how quickly the flies adjusted their daily activity to match the new light/dark cycle. By measuring how often the flies crossed an infrared beam positioned in the center of the vial, the researchers could track daily patterns of activity. They showed that the flies missing Rh7 took significantly longer to adjust than the normal, wild type flies. The researchers also examined the effect of light pulses in the middle of the night, which disrupt the normal circadian cycle, and again found that the readjustment took longer in flies missing Rh7. The central pacemaker neurons were already known to have a light sensor called cryptochrome, but the ability of flies who were genetically engineered to lack cryptochrome to regulate light/dark cycles is only partially impaired. So, the researchers suspected that another molecule might be involved—and that turns out to be Rh7, which is more light-sensitive than cryptochrome. "It appears Rh7 provides a more sensitive way of detecting light and setting circadian rhythms," explained Montell. However, more research is still needed. A light sensor in the brain makes sense in the fruit fly, because light can pass through the cuticle covering the head. But what could opsins be doing in the mammalian brain, where light may not effectively penetrate the skull? Montell suggested that the fly's central pacemaker neurons may correspond to a type of cell in the mammalian eye, rather than cells in the mammalian brain. In the eye, retinal ganglion cells (RGCs) relay signals from light-sensing rods and cones and to the brain via the optic nerve. But about 1 percent of RGCs are intrinsically photosensitive (ipRGCs). These ipRGCs, which contain melanopsin (another type of light-sensitive pigment), do not have roles in image formation but are important for the regulation of circadian rhythms. Due to their similar function and similar molecular features, Montell believes that the fly's central pacemaker neurons expressing Rh7 are the equivalent of mammalian ipRGCs. However, a mystery remains as to why opsins are also expressed in the mammalian brain and spinal cord, where they may not receive sufficient light to be light activated. Explore further: Team made new discoveries at the cellular and molecular levels about how the eye processes light More information: Ni JD, Baik LS, Holmes TC, Montell C. 2017. A rhodopsin in the brain functions in circadian photoentrainment in Drosophila. Nature, nature.com/articles/doi:10.1038/nature22325


News Article | May 10, 2017
Site: www.eurekalert.org

Six biological pigments called rhodopsins play well-established roles in light-sensing in the fruit fly eye. Three of them also have light-independent roles in temperature sensation. New research shows that a seventh rhodopsin, Rh7, is expressed in the brain of fruit flies where it regulates the fly's day-night activity cycles. The study appears in Nature and was funded by the National Eye Institute, part of the National Institutes of Health. "Rh7 is the first example of a rhodopsin that is important in setting circadian rhythms by being expressed in the central brain, rather than the eye," said Craig Montell, Ph.D., Duggan Professor of Molecular, Cellular and Developmental Biology at the University of California Santa Barbara and senior author of the study. This newly discovered role for Rh7 could have clinical implications down the road. "Identifying new roles for light-sensitive opsins is essential for understanding degenerative retinal disorders and developing potential new treatments," said Lisa Neuhold, Ph.D., program director at the National Eye Institute. Rhodopsins, discovered in the 1870s, are well-known for their important role in light-sensing and image formation. The six previously known fly rhodopsins account for the full function of photoreceptor cells in the fly's eyes, so although the fruit fly genome contained the sequence of a seventh rhodopsin, the role of Rh7 was unclear. To investigate the role of Rh7, Montell and collaborators at the University of California, Irvine, first confirmed that Rh7 sensed light by doing genetic experiments that replaced Rh1, the primary light-sensor in photoreceptor cells of the fly eye, with Rh7. The researchers found that Rh7 could functionally substitute for Rh1 in flies missing Rh1, as measured by electroretinogram, which is an extracellular recording of a neural signal in the fly eye in response to light. Next, the researchers used antibodies recognizing Rh7 to determine its expression pattern. They found that it was expressed in the brain's central pacemaker neurons, which play a role in regulating circadian rhythms. Montell and his team reared fruit flies under a 12-hour light/12-hour dark cycle, then extended one light cycle to 20 hours and measured how quickly the flies adjusted their daily activity to match the new light/dark cycle. By measuring how often the flies crossed an infrared beam positioned in the center of the vial, the researchers could track daily patterns of activity. They showed that the flies missing Rh7 took significantly longer to adjust than the normal, wild type flies. The researchers also examined the effect of light pulses in the middle of the night, which disrupt the normal circadian cycle, and again found that the readjustment took longer in flies missing Rh7. The central pacemaker neurons were already known to have a light sensor called cryptochrome, but the ability of flies who were genetically engineered to lack cryptochrome to regulate light/dark cycles is only partially impaired. So, the researchers suspected that another molecule might be involved -- and that turns out to be Rh7, which is more light-sensitive than cryptochrome. "It appears Rh7 provides a more sensitive way of detecting light and setting circadian rhythms," explained Montell. However, more research is still needed. A light sensor in the brain makes sense in the fruit fly, because light can pass through the cuticle covering the head. But what could opsins be doing in the mammalian brain, where light may not effectively penetrate the skull? Montell suggested that the fly's central pacemaker neurons may correspond to a type of cell in the mammalian eye, rather than cells in the mammalian brain. In the eye, retinal ganglion cells (RGCs) relay signals from light-sensing rods and cones and to the brain via the optic nerve. But about 1 percent of RGCs are intrinsically photosensitive (ipRGCs). These ipRGCs, which contain melanopsin (another type of light-sensitive pigment), do not have roles in image formation but are important for the regulation of circadian rhythms. Due to their similar function and similar molecular features, Montell believes that the fly's central pacemaker neurons expressing Rh7 are the equivalent of mammalian ipRGCs. However, a mystery remains as to why opsins are also expressed in the mammalian brain and spinal cord, where they may not receive sufficient light to be light activated. The work was supported by grants from the National Eye Institute (EY008117), the National Institute on Deafness and Other Communication Disorders (DC007864), and the National Institute of General Medical Sciences (GM102965 and GM107405). Ni JD, Baik LS, Holmes TC, Montell C. 2017. A rhodopsin in the brain functions in circadian photoentrainment in Drosophila. Nature XXX NEI leads the federal government's research on the visual system and eye diseases. NEI supports basic and clinical science programs to develop sight-saving treatments and address special needs of people with vision loss. For more information, visit https:/ . About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.


News Article | May 10, 2017
Site: www.eurekalert.org

Anyone who has experienced jet lag knows that changing time zones can wreak havoc on our circadian rhythms. Modulated by external cues such as sunlight and temperature, the roughly 24-hour cycles in our physiological processes are extremely sensitive. Humans aren't the only creatures whose circadian rhythms are dictated by light. The tiny Drosophila melanogaster -- known more commonly as the fruit fly -- sets its regular day-and-night-activity cycles in response to light. What's more, fruit flies also experience jetlag if they experience a sudden shift in the length of one of the day or night cycles. That makes Drosophila so instructive for studying the mechanisms underlying those circadian patterns. Using fruit flies as a model organism, the Craig Montell Lab at UC Santa Barbara has made an unexpected discovery about rhodopsin -- a light-sensitive receptor protein common to humans and flies that regulates circadian rhythms through expression in the central brain. The findings are published in the journal Nature. "Rh7 is the first example of a rhodopsin expressed in the central brain that is important in setting circadian rhythms," said senior author Craig Montell, the Duggan Professor in UCSB's Department of Molecular, Cellular and Developmental Biology. "Mammalian opsins are also expressed in many parts of the brain, but their roles are unknown." Rhodopsins play well-established roles in image formation in both human and fly eyes. In the fruit fly, six rhodopsins are responsible for the full function of photoreceptor cells in the insects' eyes. But the role of the seventh, Rh7, was uncharacterized -- until now. The Montell group has demonstrated that Rh7 functions as a light sensor that governs daily day-and-night activity cycles. "The discovery that Rh7 functions in circadian rhythms through expression in the central brain was unexpected," explained lead author Jinfei Ni, a UCSB graduate student. "It's also exciting because this finding expands the roles of these lights sensors, which were originally discovered more than 100 years ago." To determine the role of Rh7, Montell, Ni and two collaborators at UC Irvine first confirmed that Rh7 was a real light sensor. They replaced Rh1 -- the primary light sensor in the photoreceptor cells of the fly's compound eye -- with Rh7 and found it was a suitable substitute. Next, the researchers established the expression pattern of Rh7 by demonstrating that it was present in the brain's central pacemaker neurons. They then performed a series of behavioral studies demonstrating a role for Rh7 in regulating circadian rhythms. In one set of experiments, the scientists maintained the flies on 12-hour day and 12-hour night cycles and then extended one of the day cycles to 20 hours. Normal flies exhibited jet lag but adjusted within a day or two. However, mutant flies missing Rh7 experienced much more severe jetlag that persisted for many days. Montell posited that the fly's central pacemaker neurons may correspond to a special type of cell in the mammalian eye. In mammals, retinal ganglion cells (RGCs) receive signals from rods and cones -- the light-sensing cells that let us see images -- and transmit those signals to the brain via the optic nerve. Only about 1 percent of RGCs are intrinsically photosensitive. These ipRGCs, which contain melanopsin -- a visual pigment more akin to fly visual pigments than those in rods and cones -- don't have roles in image formation. But they are important for the photoentrainment of circadian rhythms. Due to their similar function and molecular features, Montell suggests that the fly's central pacemaker neurons expressing Rh7 are the equivalent of mammalian ipRGCs. A light sensor in the central brain works in the fruit fly, because light can pass through the thin cuticle covering the insect's head. But what could opsins be doing in the mammalian brain? Is it possible that sufficient light penetrates the skull to activate rhodopsins? Montell and colleagues hope additional research will provide an answer. This work was supported by grants from the National Eye Institute and the National Institute on Deafness and other Communication Disorders.


News Article | November 23, 2016
Site: www.eurekalert.org

A biologist, an engineer and a computer scientist are among the newest members of the prestigious organization Three UC Santa Barbara faculty members have been elected to the American Association for the Advancement of Science (AAAS) for 2016. Biologist Kathleen Foltz, engineer Kaustav Banerjee and computer scientist Divyakant Agrawal have each been named fellows of the prestigious organization. Election as an AAAS Fellow is an honor bestowed upon AAAS members by their peers. The UCSB professors join 388 other newly elected members to AAAS for 2016. "It is a special honor to congratulate three of our colleagues on their election to the American Association for the Advancement of Science," said UCSB Chancellor Henry T. Yang. "Professors Agrawal, Banerjee, and Foltz join the ranks of distinguished fellows at one of the world's foremost scientific societies -- one with a strong tradition of promoting collaboration, defending scientific freedom, encouraging scientific responsibility and supporting scientific education. "This prestigious honor highlights their pioneering contributions, as recognized by peers in the same fields. We are immensely proud and honored to have them as scientific leaders and colleagues on our campus." Foltz, a professor in UCSB's Department of Molecular, Cellular and Developmental Biology, was cited among her peers in the association's section on biological sciences "for distinguished contributions to the developmental and cell biology of fertilization and egg activation, and in mentoring, outreach, education and undergraduate research in STEM fields." Foltz's research focuses on molecular- and cellular-level activity and signaling at the moment of fertilization and oocyte activation. She has been named a Searle Scholar and a National Science Foundation Faculty Fellow. She also is the recipient of UCSB's Plous Award, the Chancellor's Award for contributions to undergraduate research and the Distinguished Teaching Award. Foltz also holds an appointment at UCSB's Marine Science Institute, and is interim dean of the campus's College of Creative Studies. A professor in the Department of Electrical and Computer Engineering, Banerjee was recognized in AAAS's section on engineering "for distinguished contributions to nanoelectronics, particularly for pioneering devices and interconnects with nanomaterials, and innovating circuit and chip design concepts, all advancing toward ultra-energy-efficient electronics." The director of UCSB's Nanoelectronics Research Lab, Banerjee's research interests include nanometer-scale issues in complementary metal-oxide-semiconductor very large-scale integrated circuits as well as emerging nanotechnology. A fellow of the American Physical Society and the Institute of Electrical and Electronics Engineers (IEEE), he is the recipient of the IEEE Kiyo Tomiyasu Award and the Friedrich Wilhelm Bessel Research Award from the Humboldt Foundation. Banerjee is also affiliated with the California Nanosystems Institute and the Institute for Energy Efficiency at UCSB. Agrawal's "contributions to the design and development of scalable fault-tolerant infrastructures for large scale data and information" were cited by AAAS in its section on information, computing and communication. A professor of computer science, Agrawal focuses his research in the areas of database systems, distributed computing, data warehousing and large-scale information systems. His current interests include scalable data management and data analysis in cloud computing environments, and security and privacy of data in the cloud. Agrawal is a fellow of the Association of Computing Machinery and of the IEEE. He is the recipient of Best Paper awards from IEEE and serves on editorial boards of several journals and publications. He also is the recipient of a UCSB Graduate Mentor Award and is the director of Engineering Computing Infrastructure at UCSB's College of Engineering. Foltz, Banerjee and Agrawal will be presented with official certificates and gold and blue (representing science and engineering, respectively) rosette pins on Saturday, Feb. 18, during the 2017 AAAS Annual Meeting in Boston, Mass.


News Article | February 23, 2017
Site: www.eurekalert.org

A potentially life-saving treatment for sepsis has been under our noses for decades in the non-steroidal anti-inflammatory drugs (NSAIDs) most people have in their medicine cabinets, a new University of Colorado Boulder study suggests. Each year more than 1 million people in the United States contract sepsis, an overwhelming immune response to infection. It kills as many as half of those who contract it, sometimes within days, according to the National Institutes of Health. As the number of cases rises, particularly in intensive care units, pharmaceutical companies have been scrambling to develop a drug to combat the condition. "NSAIDS like ibuprofen and aspirin are among the most prevalent pharmaceuticals worldwide, with over 30 billion doses taken annually in the United States alone. But their precise mechanisms of action are not entirely understood," said Hang Hubert Yin, a biochemistry professor at CU Boulder's BioFrontiers Institute and lead author of the new paper, published today in Cell Chemical Biology. "We provide the first evidence for a novel mechanism of action for NSAIDS, one we believe could have a direct impact on people's lives." Researchers have long known that NSAIDs work in part by inhibiting an enzyme called cyclooxygenase (COX). They've also known that these NSAIDs can come with serious side effects. Some NSAIDs have been removed from the market after showing they boosted risk of heart attack and stroke. But Yin's research found that a subgroup of NSAIDs also act strongly and independently on another family of enzymes, caspases, which reside deep within the cell and have recently been found to play a key role in aggressive immune responses, like sepsis. "For instance, some chemicals derived from bacteria actually penetrate the cell and trigger the caspase response, prompting the cell to commit suicide. This also is known as apoptosis," said Yin. "Such activation, in turn, potentially causes inflammation." After the disappointing failure of late-stage clinical trials of anti-sepsis drugs targeting an immune receptor called toll-like receptor 4 (TLR4), located on the surface of cells, Yin and other scientists began to wonder if the key to halting the disease was to develop an antiseptic therapy that simultaneously targets caspases. As a first step, his team screened 1,280 existing FDA-approved drugs for caspase-inhibiting activity. Of the 27 that lit up, half were NSAIDs. NSAIDs also comprised eight of the top 10 most potent caspase inhibitors. "It was a complete surprise," said Yin. He and study co-author Ding Xue, a professor in the department of Molecular Cellular and Developmental Biology, then used biochemical and biophysical assays in the lab, as well as experiments with roundworms to test the theory further. "We showed that NSAIDs were effective in delaying cell death in worms, presumably by blocking caspase activity." It remains questionable whether existing NSAIDs, perhaps in higher doses, could be used to treat sepsis. The risk of side effects may be too great, said Yin. But he is already working on follow-up studies looking at whether new sepsis drugs could be developed combining caspase-inhibiting NSAIDS and TLR4 inhibitors. NSAIDs could also potentially be repurposed to address other conditions, including rheumatoid arthritis and neuro-degenerative diseases. "To think about the wide potential applications of these NSAID drugs is very exciting," Yin said. He hopes the research will also help scientists better understand why NSAIDs cause serious side effects like liver, kidney and cardiovascular problems, so they can develop safer next-generations versions. The National Institutes of Health funded the study.


News Article | November 1, 2016
Site: www.sciencedaily.com

A new University of Colorado Boulder study shows for the first time the final stages of how mitochondria, the sausage-shaped, power-generating organelles found in nearly all living cells, regularly divide and propagate. In 2011, CU Boulder Associate Professor Gia Voeltz and her colleagues surprisingly found that endoplasmic reticulum (ER), another cell organelle, branches through cytoplasm like a spider web, wrapping around other organelles including mitochondria. They discovered that once an ER tentacle touches a single mitochondrion and initiates constriction, a cell protein called a dynamin-related protein, or Drp1, is recruited to further constrict the mitochondria at the spot of ER contact. Here is the new twist: Voeltz's team has now shown that once the squeeze is on the mitochondria by the Drp1 protein, a second protein -- called Dynamin-2, or Dyn2 -- is recruited to finish the job in a process called fission, splitting the organelle in two. Shaped like tiny springs, the dynamin proteins encircle the mitochondria and squeeze, somewhat like a person squeezing and twisting an elongated balloon into two halves. Both proteins are required for mitochondrial fission to occur since Drp1 is only strong enough to squeeze the mitochondria down to a certain size, and Dyn2 can only finish what Drp1 started after the constriction band is sufficiently shrunk. "Our findings change what everyone has believed about mitochondrial division," said postdoctoral fellow Jason Lee, first author on the study. "Now we know that it takes at least three different constriction steps in order to ultimately divide mitochondria." A paper on the subject was published online in Nature on Oct. 31. In addition to Voeltz and Lee, other CU Boulder paper contributors include postdoctoral fellow Laura Westrate, graduate student Haoxi Wu and researcher Cynthia Page. All study authors are in the Department of Molecular, Cellular and Developmental Biology. Floating around in almost all living cells, mitochondria vary in number from dozens to several thousand. Muscle cells, for example, have large numbers of mitochondria because of their high energy needs. New mitochondria are created when cells signal the need for more energy. Mitochondria also carry a small amount of DNA material passed down maternally. Mitochondria are important for a host of reasons. They generate energy in cells, they can play a role in longevity and they are crucial for blood sugar maintenance and fat loss. Damaged mitochondria can cause problems in cells of the brain, liver, heart, skeletal muscles and respiratory systems. The new study was funded by grants from the National Institutes of Health. The study results are important because a better understanding of mitochondrial division is a step closer to understanding what might change in cells under pathological conditions like cancer, said Wu. "The ability of our cells to efficiently convert nutrients into energy is rooted in the cell's ability to manage the shape, number and positioning of mitochondria through a balance of fusion and division," said Lee. "This balance goes awry in cancer and neurodegeneration."

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