Category Archives: Cell Biology

Light Offers New Way to Control Cell Biology – R & D Magazine

Biochemists have seen the light in developing a new way to control biology at the cellular level.

Researchers at the University of Alberta have developed a tool called a photocleavable protein that breaks into two pieces when exposed to light, allowing scientists to study and manipulate activity inside cells in new and different ways.

The scientists first used the photocleavable protein to link cellular proteins to inhibitors in a process known as caging, preventing the cellular proteins from performing their usual function.

"By shining light into the cell, we can cause the photocleavable protein to break, removing the inhibitor and uncaging the protein within the cell," lead author Robert Campbell, professor in the Department of Chemistry, said in a statement.

Once the protein is uncaged, it can begin to perform its normal function inside the cell.

The tool is relatively easy to use and widely applicable for other research that involves controlling processes inside a cell.

According to Campbell, the power of light-sensitive proteins is that they can be used to study the inner workings of any living cell. For example, ontogenetic tools are widely used to activate brain activity in mice.

"We could use the photocleavable protein to study single bacteria, yeast, human cells in the lab or even whole animals such as zebrafish or mice," Campbell said. "To put these proteins inside an animal, we simply splice the gene for the protein into DNA and insert it into the cells using established techniques."

The research team is making the gene for the photocleavable on Addgenea global archive and depository of molecular biology resources.

"We want to provide new ways to learn about cell biology," Campbell said. "I see countless potential applications for research and future investigationfrom looking at which cells become which tissues in development biology, to investigating the possibilities of gene-editing technology."

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Light Offers New Way to Control Cell Biology - R & D Magazine

Fat cells step in to help liver during fasting – Medical Xpress

March 17, 2017 A UT Southwestern study determined that the metabolite uridine helps the body regulate glucose. This graphic depicts how the bodys fat cell-liver-uridine axis works to maintain energy balance. Credit: UT Southwestern Medical Center

How do mammals keep two biologically crucial metabolites in balance during times when they are feeding, sleeping, and fasting? The answer may require rewriting some textbooks.

In a study published today in Science, UT Southwestern Medical Center researchers report that fat cells "have the liver's back," so to speak, to maintain tight regulation of glucose (blood sugar) and uridine, a metabolite the body uses in a range of fundamental processes such as building RNA molecules, properly making proteins, and storing glucose as energy reserves. Their study may have implications for several diseases, including diabetes, cancer, and neurological disorders.

Metabolites are substances produced by a metabolic process, such as glucose generated in the metabolism of complex sugars and starches, or amino acids used in the biosynthesis of proteins.

"Like glucose, every cell in the body needs uridine to stay alive. Glucose is needed for energy, particularly in the brain's neurons. Uridine is a basic building block for a lot of things inside the cell," said Dr. Philipp Scherer, senior author of the study and Director of UT Southwestern's Touchstone Center for Diabetes Research.

"Biology textbooks indicate that the liver produces uridine for the circulatory system," said Dr. Scherer, also Professor of Internal Medicine and Cell Biology. "But what we found is that the liver serves as the primary producer of this metabolite only in the fed state. In the fasted state, the body's fat cells take over the production of uridine."

Basically, this method of uridine production can be viewed as a division of labor. Researchers found that during fasting, the liver is busy producing glucose and so fat cells take over the role of producing uridine for the bloodstream. These findings were replicated in human, mouse, and rat studies.

Although uridine has many roles, this study is the first to report that fat cells produce plasma uridine during fasting and that a fat cell-liver-uridine axis regulates the body's energy balance.

Study lead author Dr. Yingfeng Deng, Assistant Professor of Internal Medicine, found that blood uridine levels go up during fasting and down when feeding. During feeding, the liver reduces uridine levels by secreting uridine into bile, which is transferred to the gallbladder and then sent to the gut, where it helps in the absorption of nutrients.

"It turns out that having uridine in your gut helps you absorb glucose; therefore uridine helps in glucose regulation," Dr. Scherer said.

The uridine in the blood works through the hypothalamus in the brain to affect another tightly regulated system body temperature, Dr. Scherer added. It appears that only uridine made by fat cells reduces body temperature, he said.

Among the study's other key findings:

Blood uridine levels are elevated during fasting and drop rapidly during feeding. Excess uridine is released through the bile.

The liver is the predominant uridine biosynthesis organ, contributing to blood uridine levels in the fed state.

The fat cells dominate uridine biosynthesis and blood levels in the fasted state.

The fasting-induced rise in uridine is linked to a drop in core body temperature driven by a reduction in the metabolic rate.

In dietary studies, the researchers found that prolonged exposure to a high-fat diet blunted the effects of fasting on lowering body temperature, an effect also associated with obesity. Further testing indicated those findings were due to the reduced elevation in uridine in response to fasting, said Dr. Deng, also a member of the Touchstone Diabetes Center.

Future research questions include studying the effects of feeding-induced reductions in uridine levels in organs that rely heavily on uridine from plasma, such as the heart, and whether bariatric surgery affects blood uridine levels.

"Our studies reveal a direct link between temperature regulation and metabolism, indicating that a uridine-centered model of energy balance may pave the way for future studies on uridine balance and how this process is dysregulated in the diabetic state," Dr. Scherer said.

Explore further: Size matters when it comes to keeping blood sugar levels in check

More information: Yingfeng Deng et al. An adipo-biliary-uridine axis that regulates energy homeostasis, Science (2017). DOI: 10.1126/science.aaf5375

How do mammals keep two biologically crucial metabolites in balance during times when they are feeding, sleeping, and fasting? The answer may require rewriting some textbooks.

Daily screen time of three or more hours is linked to several risk factors associated with the development of diabetes in children, finds research published online in the Archives of Disease in Childhood.

Jason Dyck has long believed in the beneficial properties of resveratrola powerful antioxidant produced by some plants to protect against environmental stresses. The professor of pediatrics at the University of Alberta ...

The age at which girls start menstruating could flag a later risk of diabetes during pregnancy, according to a University of Queensland study

Short bursts of high-intensity exercise could help people with non-alcoholic fatty liver disease reduce their risk of type 2 diabetes.

A diet designed to imitate the effects of fasting appears to reverse diabetes by reprogramming cells, a new USC-led study shows.

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Fat cells step in to help liver during fasting - Medical Xpress

Progress in treating hearing loss – Harvard Gazette

Inside a bony structure that spirals like a snail shell in a humans inner ear, roughly 15,000 hair cells receive, translate, and then ship sound signals to the brain. Damage to these cells from excessive noise, chronic infections, antibiotics, certain drugs, or the simple passing of time can lead to irreparable hearing loss.

Harvard Stem Cell Institute (HSCI) researchers at Brigham and Womens Hospital (BWH) and Massachusetts Eye and Ear Infirmary and colleagues from Massachusetts Institute of Technology (MIT) have developed an approach to replace damaged sound-sensing hair cells, which eventually may lead to therapies for people who live with disabling hearing loss.

In a recent Cell Reports study, the researchers identified a small molecule cocktail that increased the population of cells responsible for generating hair cells in the inner ear. Unlike hair on the human head, the hair cells lining that bony structure, called the cochlea, do not regenerate.

HSCI principal faculty Jeff Karp, HSCI affiliate faculty Albert Edge, and MITs Robert Langer were co-corresponding authors of the study. Will McLean, a postdoctoral fellow in the Edge lab, and Xiaolei Yin, an instructor in medicine at BWH, were co-first authors.

In 2012, Edge and colleagues identified a population of stem cells, characterized by an Lgr5+ marker, which scientists could turn into hair cells in a dish. A year later, Edge had converted the resident population of these cells in mice into hair cells, though the ability to restore hearing using this approach has been limited.

The problem is the cochlea is so small and there are so few cells that it creates a bottleneck limiting the number and types of experiments researchers could perform, said Edge, director of the Tillotson Cell Biology Unit at Mass. Eye and Ear and a professor of otolaryngology at Harvard Medical School (HMS).

However, by exposing Lgr5+ cells isolated from the cochlea of mice to the small molecule cocktail, the researchers were able to create a 2,000-fold increase in the number of stem cells.

Those molecules were a key to unlocking this regenerative capability, said Karp, who is also a bioengineer at BWH and an associate professor of medicine at HMS.

Inspired by creatures with significant regenerative potential, including lizards and sharks, Karps lab initially turned to one of the bodys most highly regenerative tissues, the gastrointestinal lining, which completely replaces itself every four to five days. Central to this process is the paneth cell, neighbor to the intestinal stem cells that are responsible for generating all mature cell types in the intestine. The paneth cells effectively tell the stem cells, also characterized by their Lgr5+ markers, when to turn on and off.

Karp and his colleagues at MIT looked at the basic biology of the ties between paneth cells and intestinal stem cells and identified small molecules that could communicate directly with and control the Lgr5+ stem cells.

While we were developing the approach for the intestinal cells, we demonstrated it also worked in several other tissues with the Lgr5+ stem cells and progenitors, including the inner ear, Karp said.

When the researchers coupled the cocktail with established differentiation protocols, they were able to generate large quantities of functional hair cells in a petri dish. Using protocols from the Edge lab, the researchers then thoroughly characterized the differentiated cells to demonstrate they were functional hair cells. Researchers tested the cocktail on newborn mice, adult mice, non-human primates, and cells from a human cochlea.

We can now use these cells for drug screening as well as genetic analysis, Edge said. Our lab is using the cells to better understand the pathways for expansion and differentiation of the cells.

Additionally, the small molecule cocktail may also be turned into a therapeutic treatment. Karp has co-founded Frequency Therapeutics, which plans to use insights from these studies to develop treatments for hearing loss. The team hopes to begin human clinical testing within 18 months.

Not only is it a potential therapeutic that could be relevant for the restoration of hearing, but this approach is a platform, said Karp. The concept of targeting stem cells and progenitor cells in the body with small molecules to promote tissue regeneration can be applied to many tissues and organ systems.

By Alvin Powell, Harvard Staff Writer | March 15, 2017

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Progress in treating hearing loss - Harvard Gazette

Researchers take important step forward in disabling cancer cells … – News-Medical.net

March 10, 2017 at 1:38 PM

Recent study out of the University of Ottawa opens door for new disease therapies in cancer, ALS, Fragile X Syndrome and others.

Part of what makes cancer cells so devastating is their ability to fight back against treatments -- sometimes they work, sometimes they don't. But what if we could take away cancer cells' defences altogether?

Researchers from the University of Ottawa have taken an important step forward to doing just that. Dr. Kristin Baetz says the results of a three-way research collaboration could open doors to new therapeutics to treat a variety of diseases, including cancer.

Dr. Baetz is an associate professor at uOttawa's Faculty of Medicine and Director of the Ottawa Institute of Systems Biology. Her lab studies stress granules (SGs), which are structures produced by the body's cells to protect against environmental stressors. Unfortunately, SGs also help cancer cells defend themselves against chemotherapeutic treatments, which can then lead to resistance to the common therapy.

"The first step in figuring out how to prevent this from happening is to understand how stress granules are formed and disassembled," explains Dr. Baetz, "and we now have key information."

Using yeast cells, her lab has identified a class of enzymes that play an active role in regulating SG formation. Deactivating this class of enzyme has a direct correlation to lowering SG levels.

Yeast cells are a highly relevant source of information about human cells as they mimic human cell biology.

"On the surface we may be very different, but at the cellular level humans and yeast are very much the same," says Dr. Baetz. "Given that similarity, our research is of direct relevance to human cancer biology, and metabolic and neurodegenerative diseases."

The findings come at an opportune time, when a new group of drugs are being developed against these enzymes. When administered to the yeast cells, Dr. Baetz found, the new drugs were successful in lowering SG production.

Through collaboration with labs of mammalian cell biologists and cancer specialists, the team applied their findings from yeast cells to a breast cancer cell line -- and again showed the drugs had the effect of reducing SGs.

"We've discovered one way to decrease stress granule formation, plus we have therapeutics -- so we're well positioned to explore how this strategy might work on diseases," Dr. Baetz says.

The research collaboration between the three labs has led to a paper being published in PLOS Genetics. The paper highlights the research efforts of the labs of Dr. Baetz, professor Jocelyn Ct, and assistant professor Morgan Fullerton, all of uOttawa's Faculty of Medicine.

Dr. Baetz anticipates her team's work may lead to many new avenues of research, and is optimistic with regards to the fight to disarm the warriors that are cancer cells.

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Researchers take important step forward in disabling cancer cells ... - News-Medical.net

Researchers discover intestinal quiescent stem cells that are resistant to chemotherapy – News-Medical.net

March 10, 2017 at 7:49 PM

The intestine has a high rate of cellular regeneration due to the wear and tear originated by its function degrading and absorbing nutrients and eliminating waste. The entire cell wall is renewed once a week approximately. This explains why the intestine holds a large number of stem cells in constant division, thereby producing new cell populations of the various types present in this organ.

Researchers at the Institute for Research in Biomedicine (IRB Barcelona) headed by ICREA investigator Eduard Batlle, head of the Colorectal Cancer Laboratory, have discovered a new group of intestinal stem cells with very different characteristics to those of the abundant and active stem cells already known in this organ. Performed in collaboration with the Centro Nacional de Anlisis Genmico (CNAG-CRG), the study has been published in Cell Stem Cell. These new group of stem cells are quiescent, that is to say, they do not proliferate and are apparently dormant.

The researchers describe them as a reservoir of stem cells--it is estimated that there is one quiescent cell for every 10 active intestinal stem cells. In healthy conditions, these cells have no apparent relevant function. However, they are important in situations of stress, , for example, after chemotherapy, in inflammatory processes, and in tissue infections--all conditions in which the population of "normal/active" stem cells is depleted. These quiescent cells would serve to regenerate the organ by giving rise to the various types of cells present in the intestine, renewing the population of "normal/active" stem cells, and restoring balance to the tissue.

Eduard Batlle explains that the discovery of quiescent stem cells in the intestine reveals that stem cell biology is more complex that previously appreciated and that it does not follow ahierarchical model of cell organisation. "In intestinal cell hierarchy, there are no cells above others, so the two populations are in a continual balance to ensure the proper function of the organ".

Most drugs against cancer have a secondary effect on the cells that are dividing in our tissues. "Because quiescent stem cells divide infrequently, they are resistant to many types of chemotherapy and they regenerate the tissue that this treatment has damaged," explains Eduard Batlle, head of one of the labs of international prestige in research into intestinal stem cells and their involvement in colorectal cancer.

Quiescent cells are present in many kinds of tissue. However, in spite of their relevance in tissue regeneration, increasing evidence points to their involvement in tumour development. "It is difficult to study these cells, mainly because they are scarce and there are technical limitations with respect to monitoring, straining and distinguishing them from the others," explains Francisco Barriga, first author of the study and current postdoctoral fellow at the Memorial Sloan Kettering Cancer Center in New York.

Using advanced techniques, such as genetic tracing of cell lineages and transcriptomic analysis of individual cells, performed by CNAG-CRG and the Bioinformatics and Biostatistics Unit at IRB Barcelona, the group has identified the distinct genetic programme used by quiescent stem cells with respect to normal intestinal ones. This work has been done over six years.

The researchers have labelled this cell population with a specific marker, the Mex3a protein, which has allowed them to track it over time. "We intend to continue studying quiescent stem cells in health and disease and to discover the function of the genes that distinguish them in the colon and in other organs," says Batlle.

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Want To Play Inside A Human Cell? Genius Games To Launch A Kickstarter Campaign That Will Let You – Yahoo Finance

ST. LOUIS, March 9, 2017 /PRNewswire/ --There are many mysteries unfolding every second at the cellular level inside the human body, and the board game scientists at Genius Games want to help you unravel them in their latest hard-science based strategy game, Cytosis: A Cell Biology Game. It is the first game in the world to be designed totally around the actual structure and dynamics of the human cell, and promises a vividly visual, tactile, and interactive tour of this essential building block of life.

The creators of award-winning biology and chemistry games (as well as children's books) will take players inside a human cell in Cytosis: A Cell Biology Game, where they will compete to build enzymes, hormones and receptors and fend off attacking Viruses! In 2016,Cytosis: A Cell Biology Gamewas the highest rated game during the prestigious Stonemaier Game Design Day, a day dedicated to play-testing prototypes, game design and idea exchange within the gaming community.

Well-known inside the scientific, teaching and gaming communities, the company is thrilled to announce their upcoming Kickstarter campaign for Cytosis: A Cell Biology Game, the latest addition to its growing product portfolio of games that have been heralded by both the gaming and scientific communities. In the company's latest board game, science becomes fun and learning becomes addictive when taught by the team at Genius Games. The company has had six other successful crowdfunded projects come to market. The Kickstarter campaign for Cytosis: A Cell Biology Game aims to raise $14,500. Donors pledging $39 or more will receive a copy of the game. Find more details on Cytosis: A Cell Biology Game here, and to reserve a copy, click the "Support This Project" button.

"We are excited to return to Kickstarter to seek funding for our latest board game venture, Cytosis: A Cell Biology Game. People familiar with our other products will find the same level of quality and creativity that they've come to expect from us," noted John Coveyou, founder and director of Genius Games. "Traditionally games are only meant for entertainment and school is where you go to learn. At Genius Games we have always felt that you can make learning fun. That is our mission, to develop games that are not only a blast to play, but that also simultaneously demystify intimidating science concepts. And for a cool behind-the-scenes look into the design, and launch of the game on Kickstarter, check out my new YouTube documentary series, A Kickstarter Launch Story."

"Cytosis is a really well-designed hard science game. The worker placement works extremely well Great game!," raved Paul Salomon, an expert Board Game Geek reviewer.

In Cytosis: A Cell Biology Game, players compete to build enzymes, hormones and receptors to fend off attacking viruses inside a human cell. The player with the most Health Points at the end of the game wins!

Players utilize the available organelles within the cell to collect cellular resources such as mRNA from the Nucleus, Lipids from the Smooth E.R., ATP from the Mitochondria, or transport Carbohydrates into the cell via endocytosis through the Plasma Membrane.Players may also utilize the organelles to Translate mRNA into Proteins (either on the Free Ribosome in the Cytoplasm, or in the Rough E.R) or add glucose or lipid tags to their hormonesor hormone receptors in the Golgi Apparatus.Players score health points when they complete any of the Hormone, Receptors or Enzyme cards. For 2-5 players, ages 10 and up. The game will be available nationwide in August for $44.99 MSRP.

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About Genius GamesSt. Louis, Missouri based Genius Games was founded by John Coveyou in 2014. Genius Games is a game design company that publishes high-quality tabletop games that are both entertaining and educational. For more information, please visit https://gotgeniusgames.com/.

About John CoveyouJohn Coveyou, creator and designer of Cytosis: A Cell Biology Game, nearly dropped out of school in his teen years and spent a stint living out of his car. However, after serving in the military, he pursued his love of science at Washington University, earning his Masters in Energy, Environmental and Chemical Engineering. He later quit his posh engineering job to launch Genius Games in 2014. He now teaches courses on Game Design and Crowdfunding at Webster University in St. Louis along with running Genius Games full time.

Cytosis is the sixth science-based game created by Coveyou. His previous Kickstarter campaigns were wildly successful! Coveyou also published My FirstScience Textbooks and Science Wide Open, science storybooks for kids, which are still the fourth and sixth most funded children's book campaign to date on Kickstarter.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/want-to-play-inside-a-human-cell-genius-games-to-launch-a-kickstarter-campaign-that-will-let-you-300420868.html

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Want To Play Inside A Human Cell? Genius Games To Launch A Kickstarter Campaign That Will Let You - Yahoo Finance

Researchers Engineer Enforcer Cells That Will Take out Lethal Bacteria – Big Think

Bacteria and antibiotics have been in an arms race since the drugs were invented. But for economic reasons, fewer and fewer of these drugs are being developed today, while the fear of antibiotic-resistant bacteria is ever-growing. This, and the potential threat of a bioterror attack, where say an epidemic-causing bacteria is released into the general population, makes the need for countermeasures obvious. Johns Hopkins researchers have come up with a new way to eliminate dangerous bacteria, using beefed up cells who seek out and destroy dangerous pathogens, all on their own.

Researchers from the John Hopkins Whiting School of Engineering and the School of Medicine teamed up on this four-year project. They received a grant of $5.7 million, awarded by the federal agency DARPA (Defense Advanced Research Projects Agency). The point of the study is to create a biocontrol system that can send out single-cell enforcers to find and eliminate certain pathogens. Researchers will program amoeba cells to do so, each one micron long, about one-tenth the width of a human hair.

These amoeba are independent and travel on their own surfaces--meaning they can get potentially deadly pathogens wherever they may be. In the event they are needed, they would be emitted through a spray. As a first step, scientists hope to program the cells to go after the bacteria which causes Legionnaires disease.

It could also be used to target Pseudomonas aeruginosa, a dangerous, potentially deadly, treatment-resistant strain of pneumonia. In another scenario, specially engineered amoeba cells are unleashed by health officials if an outbreak occurs. There are other uses too. They could sterilize instruments, and studying them may even reap benefits for cancer research.

So whats DARPAs interest? These biochemical warriors may someday help dampen down or even counteract a bioterror attack. They could also be used to render contaminated soil harmless. The innovation here is that each cellular soldier is self-directed. It does not depend on an outside human operator. Principal investigator Pablo A. Iglesias likened it to a self-driving car. Iglesias is a professor of electrical and computer engineering at Johns Hopkins.

Amoebas.By C.G. Ehrenberg (Die Infusionthierchen, 1830) [Public domain], via Wikimedia Commons

Just as cruise control slows down or speeds up a car, Iglesias said, In a similar way, the biocontrol systems were developing must be able to sense where the pathogens are, move their cells toward the bacterial targets, and then engulf them to prevent infections among people who might otherwise be exposed to the harmful microbes.

Iglesias started looking into biocontrol systems 15 years ago. To develop this particular type of synthetic biology, he is teaming up with four colleagues at the school of medicine. Each is a biological chemistry expert. Douglas N. Robinson, a professor of cell biology is on the team. He likened what these amoebas do to bacteria to what humans do when they encounter freshly baked cookies. They seek to gorge themselves unabashedly.

Though the technique has a lot of potential, Iglesias admitted to the Baltimore Sun, that past experiments in the field havent actually gone very well. "People manage to do things but it takes huge amounts of effort and it's more or less random, he said. There has to be a lot of iterations before it works." Other experts say, this teams efforts are heartening, particularly due to the growing menace of antibiotic-resistant bacteria.

Researchers are using amoeba cells called Dictyostelium discoideum in their experiments. This species is commonly studied. It can be found in the damp soil of riverbeds. These microbes surround bacteria and devour them. Turns out the bacteria let off a biochemical scent that the amoeba, using a specific type of receptor, pick up.

Robinson said that their experiments must adhere to the strictest operating protocols, lest such amoeba escape into the environment and wreak havoc. If this project bears fruit, researchers believe theyll have a new tool to fight infection in hospitals, and protect society against bioterror and ecological disasters. So far, scientists are targeting only pathogens lurking outside the human body. In this contract, we are not targeting bacteria in human blood, Iglesias said. But the hope is that the techniques we develop would ultimately be useful for that.

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Researchers Engineer Enforcer Cells That Will Take out Lethal Bacteria - Big Think

In-cell NMR: A new application – Phys.Org

March 8, 2017 (a) Proteins (green) can be endogenously expressed and isotopically labelled in bacteria (b) Exogenous proteins (blue) can be delivered to X. Credit: Enrico Luchinat and Lucia Banci

The structure of biological macromolecules is critical to understanding their function, mode of interaction and relationship with their neighbours, and how physiological processes are altered by mutations or changes in the molecular environment.

Ideally, classical structural biology research should interface more with cellular biology, as it is crucial for the structural data obtained in vitro to be validated within the cellular or tissue context. A true cellular structural biology approach should allow macromolecules to be characterised directly in their native environment. Such an approach would guarantee the high significance of data obtained in vivo or in the cell with the high resolution of a structural technique.

In the Past decade, NMR spectroscopy has been applied to obtain structural and functional information on biological macromolecules inside intact, living cells. The approach, termed "in-cell NMR", utilises the improved resolution and sensitivity of modern high-field NMR spectrometers and exploits selective enrichment of the molecule(s) of interest with NMR-active isotopes.

Since its inception, in-cell NMR has gradually emerged as a possible link between structural and cellular approaches. Being especially suited to investigate the structure and dynamics of macromolecules at atomic resolution, in-cell NMR can fill a critical gap between in vitro-oriented structural techniques such as NMR spectroscopy, X-ray crystallography and single-particle cryo-EM techniques and ultrahigh-resolution cellular imaging techniques, such as cryo-electron tomography.

In a topical review IUCrJ (2017), 4, 108-118 Lucia Banci and her co-worker Enrico Luchinat , both based at the University of Florence, summarise the major advances of in-cell NMR and report the recent developments in the field, with particular focus on its application for studying proteins in eukaryotic and mammalian cells and on the development of cellular solid-state NMR.

Explore further: Catching a glimpse at enzymes on the job

More information: Enrico Luchinat et al, In-cell NMR: a topical review, IUCrJ (2017). DOI: 10.1107/S2052252516020625

AAA+ ATPases are a large family of ubiquitous enzymes with multiple tasks, including the remodelling of the cellular proteome, i.e. the ensemble of proteins in a biological cell. A subfamily, so-called unfoldases, recognize, ...

A team of scientists from MIPT, Research Center Jlich (Germany), and Institut de Biologie Structurale (France) has developed a new approach to membrane protein crystallization. For the first time, the scientists have showed ...

Currently, biologists who study the function of protein nanomachines isolate these complexes outside the cell in test tubes, and then apply in vitro techniques that allow them to observe their structure down to the atomic ...

Using 3-D electron microscopy, structural biologists from the University of Zurich succeeded in elucidating the architecture of the lamina of the cell nucleus at molecular resolution for the first time. This scaffold stabilizes ...

The first three-dimensional (3-D) structure of a human protein complex within intact mammalian cells has been obtained directly by A*STAR scientists. It could provide new opportunities in structural biology, in developing ...

A new study shows that it is possible to use an imaging technique called cryo-electron microscopy (cryo-EM) to view, in atomic detail, the binding of a potential small molecule drug to a key protein in cancer cells. The cryo-EM ...

The International Potato Center (CIP) launched a series of experiments to discover if potatoes can grow under Mars atmospheric conditions and thereby prove they are also able to grow in extreme climates on Earth. This Phase ...

EPFL scientists have carried out a genomic and evolutionary study of a large and enigmatic family of human proteins, to demonstrate that it is responsible for harnessing the millions of transposable elements in the human ...

An international research team has discovered a biochemical pathway that is responsible for the development of moss cuticles. These waxy coverings of epidermal cells are the outer layer of plants and protect them from water ...

A new study involving biologists from Monash University Australia has found that despite their very different ancestors, dolphins and crocodiles evolved similarly-shaped skulls to feed on similar prey.

A new study by G. William Arends Professor of Microbiology at the University of Illinois Bill Metcalf with postdoctoral Fellow Dipti Nayak has documented the use of CRISPR-Cas9 mediated genome editing in the third domain ...

Proteins, those basic components of cells and tissues, carry out many biological functions by working with partners in networks. The dynamic nature of these networks - where proteins interact with different partners at different ...

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In-cell NMR: A new application - Phys.Org

Genetic screening to fight the common childhood virus that causes hand, foot and mouth disease – Phys.Org

March 8, 2017 Enterovirus 71 infected cells: with the cell nuclei stained blue while the virus proteins are stained green. Credit: A*STAR Institute of Molecular and Cell Biology

The unavailability of antiviral medicines and vaccines has made outbreaks of hand, food and mouth disease (HFMD) caused by enterovirus 71 (EV71), a serious threat that affects millions worldwide. Now, an A*STAR comprehensive study has identified which human proteins in a cell are hijacked by EV71 and which try to resist its invasion. Clarifying these host-pathogen interactions could reveal new targets for antiviral therapeutics.

EV71 infections mainly affect children and can lead to aseptic meningitis, and long-term neurological complications, including polio-like paralysis. Since the EV71 genome encodes for just 11 proteins, it has cleverly evolved to exploit human cells to its advantage and guarantee its successful replication.

To check which human proteins facilitate or hinder EV71 replication, scientists at the A*STAR Institute of Molecular and Cell Biology have developed a gene 'atlas'. They screened 21,121 human genes, using a technique called small interfering RNA (siRNA). The team reported an extensive list of known and unknown classes of genes that play a role during EV71 infection.

Among the 256 so-called 'host factors' identified, several proteins help regulate the length of different stages of the cell cycle, like aurora kinase B (AURKB) and cyclin-dependent kinase 6 (CDK6). Interestingly, the virus seems to manipulate these proteins to favor its own replication. For example, by evicting CDK6 out of its workplace, the nucleus of the cell, EV71 could extend certain stages of the cell cycle to its own benefit.

Another sly mechanism used by this virus is to interfere with the cellular quality control process that discards abnormal or wrongly manufactured proteins. In this way, viral proteins can be produced inside the human cell, undisturbed.

The scientists focused on two host factors that were both shown to assist EV71 replication: N-glycanase 1 (NGLY1) and valosin-containing protein (VCP). Drugs that inhibit these two host factors also reduce the number of EV71-infected cells. VCP is probably held inside vesicular structures used by the virus to copy its genome, but it remains unknown how EV71 benefits from NGLY1.

"This is the first genome-wide siRNA screening for EV71-human factors interaction and reveals the complex interplay between the virus and the proteins of a specific human cell line," points out Justin Jang Hann Chu, lead author of the study. "Some host factors we found are shared with picornaviruses and enteroviruses infections, while others are completely new and need to be further explored. This information opens a new chapter in the development of antiviral strategies for HFMD."

Explore further: Novel mechanism for invasion of EV71 virus demonstrated

More information: Kan Xing Wu et al. Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication, Nature Communications (2016). DOI: 10.1038/ncomms13150

A new study determines glycosylation and pH-dependent conformational changes of virus receptor SCARB2 as crucial for EV71 attachment, entry and uncoating.

The first enterovirus 71 (EV71) vaccine candidate to reach phase 3 clinical testing provides young Chinese children with significant protection against disease caused by EV71, a growing public-health threat which has caused ...

(Phys.org)Viruses are just bits of DNA or RNA and proteins, but they have proved to be capable of immense destruction to human health. How have they achieved the ability to create such devastating diseases in organisms ...

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Genetic screening to fight the common childhood virus that causes hand, foot and mouth disease - Phys.Org

Scientists engineering cells to eat deadly bacteria – Phys.Org

March 7, 2017 by Carrie Wells, The Baltimore Sun

Researchers at the Johns Hopkins University are working to engineer single-cell organisms that will seek out and eat bacteria that are deadly to humans.

Their work combines the fields of biology and engineering in an emerging discipline known as synthetic biology.

Although the work is still in its infancy, the researchers' engineered amoeba cells could be unleashed one day in hospitals to kill Legionella, the bacteria that cause Legionnaire's disease, a type of pneumonia; or Pseudomonas aeruginosa, a dangerous, drug-resistant bacteria associated with various infections and other life-threatening medical conditions in hospital patients.

Because amoeba are able to travel on their own over surfaces, the engineered cells also could be used to clean soil of bacterial contaminants, or even destroy microbes living on medical instruments. If the scientists are successful at making the cells perform tasks, it also could have important implications for research into cancer and other diseases.

"We're using this as a test bed for determining do we understand how cells work to the point where we can engineer them to perform certain tasks," said Douglas N. Robinson, a professor of cell biology and a member of the Hopkins team. "It's an opportunity to demonstrate that we understand what we think we understand. I think it's an opportunity to push what we're doing scientifically to another level."

The five-member team's work began in October after it received a four-year, $5.7 million federal contract from the Defense Advanced Research Projects Agency, known as DARPA.

Douglas said they want the engineered cells to respond to dangerous bacteria the way a human might respond to the smell of a freshly baked plate of cookies - to immediately crave a cookie, walk into the kitchen and eat some.

Engineering cells to perform such tasks remains a work in progress.

"In practice it hasn't gone terribly well," said Pablo A. Iglesias, a professor of electrical and computer engineering and a member of the Hopkins team. "People manage to do things but it takes huge amounts of effort and it's more or less random. There has to be a lot of iterations before it works."

David Odde, a professor of biomedical engineering at the University of Minnesota, hailed the research as exciting, especially since antibiotic resistance is on the rise. He said the team would face many challenges.

"I think getting the cells to sense the bacteria robustly might be a challenge, and I'm sure they're aware of that," he said. "The cells have to sense something that the immune system has failed to sense."

The research could lead to new discoveries beyond what the team is focusing on, Odde said. They could learn more about how amoeba sense the bacteria and how that signals to them that they should move forward and eat, he said.

"How does the signaling inform the eating parts?" he said. "They might make new discoveries about how these cross systems talk to each other which will be really valuable for this project and many other projects."

The amoeba they are using, Dictyostelium discoideum, is commonly found in damp soil and naturally eats bacteria after sensing the biochemical scent of it. Since the amoeba eats bacteria, the researchers must program it to go after the kind of bacteria that they want it to eat, instead of other types of bacteria.

Robinson, the cell biology professor, will study how the amoeba's "legs" power movement. Peter Devreotes, another cell biology professor on the team, will study what happens in the amoeba's "brain" once it senses the bacteria nearby. Iglesias, a computational biologist, has expertise in control systems, once designing airplane controllers, and he will help design the biological controller used to steer the amoeba in the right direction.

The other two team members, Tamara O'Connor, an assistant professor in the Hopkins department of biological chemistry, and Takanari Inoue, an associate professor of cell biology, will try to ensure the amoeba go after the right bacteria and link the amoeba's "brain" and "legs."

Andre Levchenko, a professor of biomedical engineering at Yale University, said it might take a lot to "foolproof" the mechanism and that unexpected problems may arise, such as mutations in the cells.

"What would be interesting to see is how stable their new engineered organisms are. With anything that is alive and adaptable and dynamic, it's always a concern when you engineer it," Levchenko said. "I've been very impressed with this particular proposal. It's risky, but it does have a lot of elements that make me think it'll be very successful."

Dennis Discher, director of the National Cancer Institute's Physical Sciences Oncology Center at the University of Pennsylvania, said "the time is right" for this type of research.

"It's intriguing to not just think about cells in your body, but amoeba that usually are sort of good for nothing except basic biological science and repurpose them for other uses," he said.

Robinson said it may be hard to get the amoeba to move properly toward the bacteria they want it to eat because the controller could cause it to overshoot and end up too far away.

Iglesias said that under the contract with DARPA, the team will have to meet benchmarks every six months. The first benchmark was to prove that the amoeba's controller can be inserted successfully, which Iglesias said they have done.

The task was difficult because the amoeba are the size of a micron, or about one-tenth of the width of a human hair. They can also move fairly quickly, Iglesias said.

DARPA "wants you to think big and do something big, and I think in that respect it's pretty exciting," Iglesias said.

Explore further: Amoeba feast on backpacks

2017 The Baltimore Sun Distributed by Tribune Content Agency, LLC.

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Scientists engineering cells to eat deadly bacteria - Phys.Org