A new computational framework that utilizes confocal Raman spectroscopy allows 3D cell imaging with quantitative mapping of intracellular biomolecules. As Molly Stevens and co-workers report in Nature Communications , this framework provides unprecedented insight into cell biology as well as cellmaterial interactions in advanced biomaterials.
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3D bioimaging: Cells in gels - Nature.com
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Drew Endy: Endy, a Stanford biotechnologist who focuses on genetic computing, has helped drive efforts to keep synthetic biology open source.
Jay Keasling: A chemical- and bioengineer based at University of CaliforniaBerkeley, Keasling led an effort to synthetically produce aremisinin, a powerful anti-malarial drug.
Kristala Prather: Prather, an MIT professor, runs a lab working to turn microbes into chemical factories.
J. Craig Venter: After playing an important role in early efforts to sequence the human genome, Venter now heads the J. Craig Venter Institute, whose work involves, among other things, research on synthetic life forms.
Christopher Voigt: Voigt is an MIT biological engineer who has worked at the intersection of synthetic biology and CRSIPR gene editing technology.
Boundaries of species: Synthetic biologists sometimes take genetic material from one species and implant it in another. Will such transplantations challenge our ability to make sense of the unnatural world? Is it ethical to fuse organisms that would otherwise remain distinct?
Computational comparisons: Proponents of synthetic biology often suggest that we should be able to encode genetic material in much the same way that we program computers, but real lab work doesnt always bear that metaphor out. Will synthetic biology advance to the point where this comparison works in practice?
Ecological implications: Some critics of synthetic biology worry about what will happen when lab-made organisms start finding their way into the wild. Will these synthetic creations destroy already fragile ecosystems? Or will this simply be the next step in our species long-running agricultural transformation of the world?
Eugenics: As synthetic biology advances, we may gain the ability to introduce novel sequences into the human genome, allowing us to reconfigure our own offspring. What are the ethical implications of taking evolution into our own hands?
Regulatory uncertainty: At present, there are few to no legal standards specific to the practice of synthetic biology. Are we courting environmental or medical disaster in the absence of such norms? If we did impose laws, would we risk dramatically impeding the pace of progress?
BioBricks: DNA strings designed to be pieced together in synthetic biology applications.
Biofuel: A fuel generated from a living organisma primary goal for many synthetic biologists.
Carson curve: An analogue to Moores law, the Carlson curve describes the rate at which our ability to synthesize DNA is accelerating.
CRISPR: A genetic editing technique that involves copying and pasting strings of DNA.
Metabolic pathway: A sequence of chemical reactions that occur within a cell. Some synthetic biologists seek to manipulate these pathways in laboratory organisms to produce novel outputs.
Synthetic biology: An interdisciplinary research field that combines the insights of computer science, engineering, genetics, and cellular biology in an effort to reshape the building blocks of life.
A Life of Its Own by Michael Specter: In this long New Yorker article, Specter discusses some of synthetic biologys most prominent achievements.
Our Biotech Future by Freeman Dyson: In this seminal 2007 New York Review of Books essay, physicist Dyson argued that green technology could radically upset the balance of power in the world.
The Principles for the Oversight of Synthetic Biology: This collaboratively drafted document suggests a set of industrial and experimental oversight mechanisms that would be specific to the challenges of synthetic biology.
Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves by George M. Church and Ed Regis: This recent book looks at the practical promise of biotechnology as we continue to transform the microbial world.
Synthetic: How Life Got Made by Sophia Roosth: In this book, Roosth, a cultural anthropologist, discusses her study of synthetic biologists, revealing how they understand the world that they are shaping.
Why Kickstarters Glowing Plant Left Backers in the Dark by Antonio Regaldo: Revisiting the largely failed Glowing Plants project, Regaldo looks into the practical limitations of synthetic biology.
BioShock, directed by Ken Levine: This video game takes place in an underwater city whose residents modify their DNA to provide themselves with superhuman abilities.
Blood Music by Greg Bear: In this novel, biological computers infect humans, reshaping their lives and their world in the process.
Change Agent by Daniel Suarez: In the near-future world of this novel, an Interpol agent tries to fight back against a powerful biocrime syndicate after it rewrites his own genome.
Gattaca, directed by Andrew Niccol: This film plays out in a world shaped by genetic analysis and eugenics.
Orphan Black, created by Graeme Manson and John Fawcett: A powerful biotech company manipulates the lives of a group of clones in this British television series.
This article is part of the synthetic biology installment of Futurography, a series in which Future Tense introduces readers to the technologies that will define tomorrow. Each month, well choose a new technology and break it down. Future Tense is a collaboration among Arizona State University, New America, and Slate.
Photo of Drew Endy, Jay Keasling, J. Craig Venter, and Christopher Voigt by Creative Commons. Photo of Kristala Prather by MIT.
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Your Cheat-Sheet Guide to Synthetic Biology - Slate Magazine
The European Patent Office (EPO) has announced its intention to grant a broad patent for the revolutionary CRISPR-Cas9 gene-editing technology to the University of California, the University of Vienna and Emmanuelle Charpentier.
A model of the Cas9 protein cutting a double-stranded piece of DNA.
The university is thrilled with this important EPO decision, which recognizes the pioneering work of Jennifer Doudna, Emmanuelle Charpentier and their teams as the CRISPR-Cas9 inventors, and also recognizes that the original patent application covers a wide range of cell types, including human cells, said Edward Penhoet, who was recently appointed a special advisor on CRISPR to the UC president and UC Berkeley chancellor. Penhoet, the cofounder and former CEO of Chiron Corp., is the associate dean of biology at UC Berkeley and a professor emeritus of molecular and cell biology.
The EPO patent will cover the single-guide CRISPR-Cas9 technology in cells of all types. The technology was invented by Jennifer Doudna, a UC Berkeley professor of molecular and cell biology, Charpentier, now director of the Max Planck Institute for Infection Biology in Berlin, and their colleagues. Applications include treatment of various human diseases, as well as veterinary, agricultural and other biotech applications. The European patent would cover some 40 countries, including France, Germany, Italy, Spain, the Netherlands and Switzerland.
The EPO has stated its intent to grant a patent with claims that encompass all cells, despite objections from third parties, including the Broad Institute, a joint research institute of Harvard University and the Massachusetts Institute of Technology.
We are excited that this patent will issue based on the foundational research we published with Emmanuelle Charpentier and the rest of our team. We look forward to the continued applications of gene-editing technology to solve problems in human health and agriculture, said Doudna, who is a Howard Hughes Medical investigator at UC Berkeley.
The CRISPR-Cas9 tool allows the precise editing of genes, and has been used in thousands of laboratories around the world to target and cut desired sequences of DNA, analogous to cutting and pasting letters or words with a word processor. This technology has already revolutionized the study of genetic diseases, and has spawned promising new therapies for blood diseases, AIDS and cancer.
What is CRISPR-Cas9 and how does it work? How do we edit genes? Jennifer Doudna, biochemist at UC Berkeley, explains (UC Berkeley video by Roxanne Makasdjian and Stephen McNally)
The EPOs notice of intent to issue the patent, as well as the UK Intellectual Property Offices grant of two similarly broad patents, are precedents for Doudna and Charpentier to receive wide-ranging patents in many countries, since many look to EPO and UK decisions for guidance in granting patents.
The UC patent application to the EPO was substantially the same as the UC patent application filed in the United States. In the U.S., UC claims covering the use of single-guide CRISPR-Cas9 technology in any setting were found to be allowable by the U.S. Patent & Trademark Office, and were placed in an interference with patents owned by the Broad Institute that cover use of the technology in eukaryotic cells. An interference is a formal legal proceeding before the Patent Trial and Appeal Board (PTAB) to determine who was the first to invent.
In a February ruling, the PTAB terminated the interference between the UC application and Broad patents, determining that the claims of the two parties did not constitute the same invention and, accordingly, the PTAB did not determine which party first invented the use of the technology in eukaryotic cells.
We disagree with the recent PTAB decision to terminate the interference between claims of the UC and the Broad Institute, and we are keeping all of our options open, including the possibility of an appeal, Penhoet said. We remain confident that when the inventorship question is finally answered, the Doudna and Charpentier teams will prevail.
The inventors listed on the European patent are Doudna; Charpentier; Martin Jinek, now at the University of Zurich; Krzysztof Chylinski of the University of Vienna; Wendell Lim of UC San Francisco; Lei Stanley Qi, now at Stanford University; and Jamie Cate, a UC Berkeley professor of molecular and cell biology.
RELATED INFORMATION
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European Patent Office to grant UC a broad patent on CRISPR-Cas9 - UC Berkeley
March 29, 2017 Figure: Visualization of myosin II filament stacks (yellow) with cross-linking protein alpha-actinin-1 (blue) in fibroblast cells using structured illumination microscopy. Myosin II filaments alternate with apha-actinin enriched domains along actin stress fibre. Credits: Mechanobiology Institute, Singapore
Researchers from the Mechanobiology Institute, Singapore (MBI) at the National University of Singapore have described, for the first time, the ordered arrangement of myosin-II filaments in actin cables of non-muscle cells. This work was published in Nature Cell Biology in January 2017.
Ordered arrangement of myosin-II filaments defined in non-muscle cells
The twitching contractions of our muscle cells are well known. They can be detected just weeks after conception as the embryonic heart begins beating. Muscle cell contractility is produced from interactions between protein-based cables of the cytoskeleton and small molecular motor proteins known as myosins.
There are over 200 types of cells within the human body, and not all need to repeatedly contract. Despite their distinct functions, nearly all cells contain the same basic protein components found in muscle cells. Importantly, most cells also exhibit some degree of slow contractility. Fibroblasts are one such example. Found in connective tissue, these cells produce the material that surrounds all cells, and ultimately defines tissue shape. Importantly, fibroblasts are also known to remodel this material, and for this, they need strength to pull against their environment.
To investigate the organisation of the cytoskeleton and its associated motor proteins in non-muscle cells, researchers from MBI analysed fibroblasts using a form of super resolution microscopy known as Structured Illumination Microscopy (SIM).
The researchers, who were led by Professor Alexander Bershadsky and Assistant Professor Ronen Zaidel-Bar, focused their investigation on the assembly of the cytoskeleton. Along with providing structural support to the cell, the cytoskeleton can also buffer stresses from the external microenvironment and give cells the power to contract and move through a tissue. These processes are possible due to the continual assembly and disassembly of the protein cables, and due to the generation of force as motor proteins pull on these cables.
When the cytoskeleton was viewed in living fibroblasts, Dr Shiqiong Hu, a postdoctoral researcher at MBI, and colleagues, discovered unique, organised patterns of motor protein filaments within large protein cable-like structures known as stress-fibres. These cables form dynamically and often bridge sites where the cells are interacting with the microenvironment.
Like ropes, these cables are made up of many individual filaments, held together by various cross-linking proteins. By watching the cytoskeleton form over time, the researchers observed how myosin-II filaments arranged into stacks that ran perpendicular to the large parallel stress fibres. These stacks alternated with regions of the 'cross-linking' protein a-actinin, which tethers individual filaments together to produce the protein cable.
How myosin-II filaments come to be stacked together within the bundled stress fibres, remains to be fully defined, however one observation from this study that may hold the answer, is the long range movement of myosin-II filaments towards each other. As the researchers propose, this attraction may result from contractile or elastic forces generated by the myosin filament stacks, which can transmit through the surrounding cytosol to individual filaments that are otherwise isolated.
The stacking of myosin-II filaments in non-muscle cells like the fibroblast is an intriguing element in the self-organisation of the cytoskeleton, and overall architecture of the cell. Fibroblast function requires the cell to be able to stretch, generate cytoskeletal protrusions and move to other regions of the connective tissue. The assembly and organisation of myosin-II into stacks permits the fibroblast to fulfill these cellular processes.
Even in non-muscle cells, the architecture of the cytoskeleton is specialised for force generation and sensing. The organisation of the cytoskeleton in non-muscle cells is strikingly similar to that in muscle cells. In both cases contractile and elastic forces are integral in establishing a functional cytoskeleton, and once formed, a pattern of repeating protein-based contractile proteins becomes evident. However, unlike in muscle cells, these structures continuously assemble and disassemble in non-muscle cells, allowing them to adapt their function, shape, and direction of movement according to the environment they find themselves in.
As observed in this study, even non-muscle cells require the strength to pull against their surroundings, and fight their way through often sticky environments. This strength comes from a highly refined system of filaments and motor proteins. Although not as strong as those found in muscle cells, their organisation in non-muscle cells allows them to remain responsive to changes in the environment, whilst providing just the right amount of force to carry out their functions.
Explore further: Cellular podiatry understanding how cells form feet
More information: Shiqiong Hu et al. Long-range self-organization of cytoskeletal myosin II filament stacks, Nature Cell Biology (2017). DOI: 10.1038/ncb3466
A study carried out by a team of researchers from the labs of Professor Alexander Bershadsky at the Mechanobiology Institute, Singapore at the National University of Singapore and Professor Gareth E Jones at King's College ...
Muscle-specific protein cofilin-2 controls the length of actin filaments in muscle cells.
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Understanding how tiny molecular motors called myosins use energy to fuel biological tasks like contracting muscles could lead to therapies for muscle diseases and cancers, says a team of researchers led by Penn State College ...
Scientists at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria and at the University of Cologne, Germany have discovered the molecular basis underlying the patterned folding and assembly of muscle proteins. ...
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Unlike most animals, sea lampreys, an invasive, parasitic species of fish damaging the Great Lakes, could become male or female depending on how quickly they grow, according to a U.S. Geological Survey study published today.
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Scientist Joanna Smeeton explores stem cell-based approaches to studying and eventually treating the common cause of cold aversion, disability and pain.
We only have treatments for the larger joints where you can provide total replacements, but a lot of people with arthritis actually get it in the joints of their hands, said Smeeton, a postdoctoral fellow in the laboratory of Gage Crump and this years Broad Fellow, the third since 2014. Currently, there really isnt that much we can do for the cartilage in these smaller joints, other than treat the symptoms with steroids or painkillers.
As part of the quest for new and better treatments, her Broad Fellowship project leverages a key discovery that she and her colleagues recently published in the journal eLife. They found that certain joints in zebrafish jaws and fins have features similar to the type of mammalian joint susceptible to arthritis.
By damaging a ligament that stabilizes the adult zebrafish jaw, she can reliably induce cartilage damage and arthritis. Just as reliably, the zebrafish can repair the damage. Smeeton aims to understand which progenitor cells are regenerating the ligament and cartilage in the zebrafish jaws, and why similar repair fails to occur in humans.
In the future, these findings may help in devising strategies to stimulate analogous progenitor cells in patients joints toward boosting cartilage and ligament regeneration, she said.
Smeeton first decided to become a scientist thanks to a very different anatomical structure: the human kidney. As a high school student in the city of St. Catharines near Niagara Falls in Ontario, she developed a fascination with this complex organ, which is composed of 1 million subunits called nephrons that filter the blood, regulate blood pressure and produce urine.
Whenever I had a science class about kidneys, I thought, Oh, nephrons are so cool! she said.
At McGill University in Montreal, she majored in anatomy and cell biology, and observed kidneys and other organs in human cadavers in the anatomy lab.
Ive always been fascinated by how intricately patterned organs are and how that actually happens during development.
Joanna Smeeton
Ive always been fascinated by how intricately patterned organs are and how that actually happens during development, she said.
For her PhD, she learned more about kidney development in a lab at Torontos Hospital for Sick Children and the University of Toronto.
During her postdoctoral studies, she expanded her focus beyond development and into the realm of regeneration.
Id been hearing talks about zebrafish for years and their amazing ability to regenerate parts of themselves that are injured or removed, she said. So I wanted to learn how to use them. I switched to studying cartilage because joint disease seemed like an area that was understudied in the context of natural regeneration and would be ripe for new treatments.
With these goals in mind, she joined the Crump Lab with a two-year postdoctoral fellowship from the California Institute for Regenerative Medicine in 2014. Since then, she has not only discovered that zebrafish can develop arthritis, but also lent her talents as a soprano to the USC University Chorus and, with her husband Jeremy, parented twins: Edie and Isaac. Theirs is a true Trojan family: Jeremy Morris graduated in 2012 with an MFA from the Peter Stark Producing Program at the USC School of Cinematic Arts.
The twins have made me even more focused in my lab work, said Smeeton, because I know that any second that Im not home with them, I should be giving my 100 percent and really drilling down on the important questions we want to ask.
As she moves ahead with her research, the Broad Fellowship provides an ideal bridge. Established as part of a $2 million gift from The Eli and Edythe Broad Foundation, the fellowship is designed to support exceptional senior postdoctoral researchers at the transition point to starting their own stem cell laboratories.
Joanna is a motivated, smart and creative researcher who is destined for success in academic research, said Crump, associate professor of stem cell biology and regenerative medicine. This prestigious fellowship gives her the freedom to pursue her novel joint regeneration project, which provides a fundamentally new type of approach toward finding cell-based cures for arthritis.
More stories about: Research, Stem Cells
Gabriel Linares seeks therapies for patients with Lou Gehrigs disease.
The condition is more widespread in the animal kingdom than scientists suspected, USC study finds.
Lori OBrien will use Broad Center support to find her niche in kidney research and regenerative medicine.
The objective of one current research proposal is to push the frontiers of stem cell and tissue engineering technologies.
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USC scientist fishes for stem cell-based arthritis treatments - USC News
Kickstarterhas always been a platform to bring your ideas to life. Over the years weve seen some great ideas and even some terrible ideas but in the end, it comes down to the backers to make it happen.
One thing Ive always enjoyed searching on Kickstarter are the different type of games (board games and video games) people or even companies try to make. Over the years weve had a chance to take a look at a few of these different type of games but one that seems really interesting isCytosis: A Cell Biology Game fromGenius Games. It combines science, in this case learning about the human bodywhere players compete to build enzymes, hormones, and receptors and fend off attacking Viruses.
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.
The Kickstarter is looking to raise $14,500 by April 13, 2017. Everyone whole pledges $39 will receivea copy of the game which will retail for $50 MSRP or a premium edition of the game if you pledge $49 which includes aincludes custom wooden shaped and silk screened mRNA, Protein, Lipid, & Carbohydrate resource tokens, an Individually Numbered copy of the game with an upgraded Metallic Ink embossed box.
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 theyve 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.
It sounds like a fun way to spend a day with friends, or even a fun game to play with your family as you learn more about the human body.
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Cytosis: A Cell Biology Game makes learning about the human cells fun - Nerd Reactor
The discovery of a chemical compound that halts the production of a small set of proteins while leaving general protein production untouched suggests a new drug search strategy: Find compounds that target undesired proteins before they are even made.
Ribosomes lined up along pieces of messenger RNA extrude proteins that curl up once they emerge from the ribosomes internal tunnel. UC Berkeley and Pfizer scientists discovered that a small molecule (black T) can kink the growing protein inside the tunnel and stall its production while leaving other protein production unaffected. Jamie Cate image.
Many of todays therapies for cancer or heart disease are monoclonal antibodies that bind and disable proteins outside the cell. The immunotherapeutic checkpoint inhibitors, such as Yervoy, block suppressor proteins, for example, unleashing the immune system to attack cancer.
But monoclonal antibodies arent effective against all proteins, cant enter cells and must be delivered via injection.
In a paper appearing today in the journal PLOS Biology, researchers at the University of California, Berkeley, and Pfizer Worldwide Research and Development report finding a small molecule that was able to block the production of a specific protein involved in LDL (low-density lipoprotein) turnover by stalling only the ribosome that produces that protein. Ribosomes are large, general-purpose molecular machines that translate genetic instructions in the form of messenger RNA into the proteins used to build cells, the enzymes in charge of cellular housekeeping, and the hormones that carry messages in and between cells.
When delivered orally to rats, the small molecule lowered LDL cholesterol levels, much the way statins do, though by a different mechanism: by lowering the production of the protein PCSK9.
While antibiotics like erythromycin are known to stall the ribosome, they halt production of most proteins, said Jamie Cate, one of two senior authors, a UC Berkeley professor of molecular and cell biology and of chemistry and a faculty scientist at Lawrence Berkeley National Laboratory.
The chemical in this instance stalls the ribosome only when its producing the protein PCSK9 and a couple of dozen others out of the tens of thousands of proteins the body produces, as shown by a relatively new technique called ribosomal profiling.
PCSK9 was just where we started. Now we can think about how to come up with other small molecules that hit proteins that nobody has been able to target before because, maybe, they have a floppy part, or they dont have a nook or cranny where you can bind a small molecule to inhibit them, Cate said. This research is saying, we may be able to just prevent the synthesis of the protein in the first place.
Cate suspects that the small molecule in the current study, a multi-ringed chlorinated compound, could serve as a template, like a key blank that can be machined to open a specific lock.
We now have this key blank that we can cut in a number of different ways to try to go after undruggable proteins in a number of different disease states, Cate said. No one really thought that would have been possible before.
Stalling the ribosome The small molecule was discovered by Pfizer labs through live-cell screening for compounds that lower production of the protein PCSK9 (proprotein convertase subtilisin kexin 9), which regulates the recycling of the LDL receptor. Knocking out the protein is known to lower blood levels of LDL cholesterol, the so-called bad cholesterol, presumably lowering risk of cardiovascular disease. PCSK9 inhibitors, mostly monoclonal antibodies, actually lower LDL better than the well-known statins, though they have to be injected into the bloodstream.
When it became clear that the chemical was acting on the ribosome, Spiros Liras, vice president of medicinal chemistry at Pfizer, approached Cate and Jennifer Doudna, both leaders in the field of ribosome function and translation, to establish a collaboration through UC Berkeleys California Institute for Quantitative Bioscience (QB3) to further investigate the questions of selectivity and mechanism of action. Cate is also director of UC Berkeleys Center for RNA Systems Biology, while Doudna is a professor of molecular and cell biology and of chemistry, a Howard Hughes Medical Institute investigator and executive director of the Innovative Genomics Institute.
Pfizer brought a significant depth of knowledge and resources to the collaboration, including fundamental cell biology, disease-relevant expertise, chemical biology and medicinal chemistry,said Liras. We aimed at building a strong cross-institutional collaboration which would complement our strengths in drug discovery with UC Berkeleys strengths in ribosome biochemistry and structural biology.
In the PLOS Biology paper, Cate, Robert Dullea at Pfizer and their teams at UC Berkeley and Pfizer describe how the drug interacts with the ribosome to halt protein production.
According to Cate, the ribosome assembles amino acids into a chain inside a tunnel that holds about 30 to 40 amino acids before the end begins to poke out of the tunnel. The chemical studied appears to bind to specific amino acid sequences of the growing protein within that tunnel in the ribosome and make them kink enough to stop progress down the tunnel, halting protein synthesis.
We found that the proteins that are stalled are too short to stick outside the ribosome, Cate said. So we think the compound is actually trapping this snake-like chain, the starting part of the protein, in the tunnel not completely blocking the tunnel, but just partially blocking it, in a way that prevents this particular protein from making its way out.
While its still unclear what the two dozen proteins affected have in common that makes them susceptible to stalling by the small molecule, Cate sees these findings as clear evidence that ribosomal stalling can occur very specifically, something most researchers thought unlikely.
We think that we now have enough understanding of the mechanism that we have our foot in the door to explore the relevance of this biology more broadly, said Cate.
Co-authors of the paper are Cate, Doudna and postdoctoral scholar Nathanael Lintner of UC Berkeley and Pfizer researchers Kim McClure, Donna Petersen, Allyn Londregan, David Piotrowski, Liuqing Wei, Jun Xiao, Michael Bolt, Paula Loria, Bruce Maguire, Kieran Geoghegan, Austin Huang, Tim Rolph and Spiros Liras.
The work was funded by Pfizer, with computing and gene sequencing assistance through resources supported by the National Institutes of Health. RELATED INFORMATION
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New drug strategy: Target ribosome to halt protein production - UC Berkeley
A species of unicellular ciliate has found a special trick to make use of the cellular machinery in seemingly impossible ways. Researchers of the NCCR "RNA & Disease -- The Role of RNA Biology in Disease Mechanisms" of the University of Bern have for the first time described a mechanism in detail how so called "junk"-DNA is transcribed before being degraded -- and this mechanism is remarkably clever.
It sounds a bit like the winning proposal in a design contest: How can small pieces of information be read when they are too short to fit into the reading apparatus? Stitch them together into a longer string and close the string to produce a handy loop that can even be read off repeatedly. That's how a little organism called Paramecium tetraurelia, a species of unicellular ciliate, organises the transcription of small excised DNA segments into RNAs, which have a regulatory function.
But the story actually goes the other way round: When Mariusz Nowacki from the Institute of Cell Biology of the University of Bern found small RNAs with a regulatory function in the elimination of segments out of the Paramecium DNA, he and his team started to investigate the molecular mechanisms -- where do these RNAs come from, and what exactly is their role? They soon found out that there seems to be a sort of a feedback loop in the deletion of DNA segments. These, previously thought to be useless pieces of DNA (also called "junk DNA"), are cut out of the genome and then degraded by the cell machinery. However, before degradation, they serve as templates for small RNAs which in turn help with cutting out more of these DNA pieces. Once started, this pyramid system keeps reinforcing itself, via the production of RNA.
Transcribing the non-transcribable
As beautiful and intriguing as this system seemed to be, the researchers were left with a serious problem: Usually, the cellular transcription mechanism needs a much longer piece of DNA to operate. So how could these small excised DNA pieces -- of the length of not even 30 base pairs -- be used as templates? Without a good explanation for this, the whole theory looked very implausible. "It was an interesting detective work," Nowacki remembers. They had a suspect -- all they needed was to pin it down. "We were not actually looking for the unknown, because we soon had an idea, and then it was all about testing that idea." And their guess proved to be right: Paramecium has figured out a way to stitch DNA pieces together randomly into strings and, once the strings have the right length (of about 200 base pairs), to connect the ends and form circular concatemers of DNA segments.
Junk or not junk?
The finding has interesting implications: DNA thought to be non-coding "junk" -- of no use for the organism whatsoever and degraded quickly after being removed from the genome -, is actually a functional template for a biologically important class of small RNAs. It is actually one of the big emerging fields in molecular biology, whether "junk" DNA is really worthless or rather, as is increasingly becoming clear, whether it actually has regulatory functions. Nowacki believes that in this work his group was for the first time able to pin down a precise mechanism for the transcription of deleted "junk" DNA -- which would strengthen the case for an inevitable name change.
"RNA & Disease -- The Role of RNA Biology in Disease Mechanisms"
The NCCR "RNA & Disease -- The Role of RNA Biology in Disease Mechanisms" studies a class of molecules that has long been neglected: RNA (ribonucleic acid) is pivotal for many vital processes and much more complex than initially assumed. For instance, RNA defines the conditions, in a given cell, under which a given gene is or is not activated. If any part of this process of genetic regulation breaks down or does not run smoothly, this can cause heart disease, cancer, brain disease and metabolic disorders.The NCCR brings together Swiss research groups studying different aspects of RNA biology in various organisms such as yeast, plants, roundworms, mice and human cells. Home institutions are the University of Bern and the ETH Zurich.
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Materials provided by University of Bern. Note: Content may be edited for style and length.
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Cut the long story short, and stitch it back together - Science Daily
What Is Cell Biology?
Cell biology is the subdiscipline of biology that studies the basic unit of life, the cell. It deals with all aspects of the cell including cell anatomy, cell division (mitosis and meiosis), and cell processes includingcell respiration, and cell death. Cell biology does not stand alone as a discipline but is closely related to other areas of biology such as genetics, molecular biology, and biochemistry.
Based on one of the basic principles of biology, the cell theory, the study of cells would not have been possible without the invention of the microscope. With the advanced microscopes of today, such as the Scanning Electron Microscope and Transmission Electron Microscope, cell biologists are able to obtain detailed images of the smallest of cell structures and organelles.
All living organisms are composed of cells. Some organisms are comprised of cells that number in the trillions. There are two primary types of cells: eukaryotic and prokaryotic cells. Eukaryotic cells have a defined nucleus, while the prokaryotic nucleus is not defined or contained within a membrane. While all organisms are composed of cells, these cells differ among organisms. Some of these differing characteristics include cell structure, size, shape, and organelle content. For example, animal cells, bacterial cells, and plant cells have similarities, but they are also noticeably different.
Cells have different methods of reproduction. Some of these methods include: binary fission, mitosis, and meiosis. Cells house an organisms genetic material (DNA), which provides instructions for all cellular activity.
Cell movement is necessary for a number of cell functions to occur.
Some of these functions include cell division, cell shape determination, fighting off infectious agents and tissue repair. Internal cell movement is needed to transport substances into and out of a cell, as well as to move organelles during cell division.
Study in the field of cell biology can lead to various career paths. Many cell biologists are research scientists who work in industrial or academic laboratories. Other opportunities include:
There have been several significant events throughout history that have led to the development of the field of cell biology as it exists today. Below are a few of these major events:
The human body has a multitude of different types of cells. These cells differ in structure and function and are suited for the roles they fulfill in the body. Examples of cells in the body include: stem cells, sex cells, blood cells, fat cells and cancer cells.
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Cell Biology - thoughtco.com
March 16, 2017 at 12:18 PM
Cells infected by the deadly Ebola virus may release viral proteins such as VP40 packaged in exosomes, which, as new research indicates, can affect immune cells throughout the body impairing their ability to combat the infection and to seek out and destroy hidden virus. The potential for exosomal VP40 to have a substantial impact on Ebola virus disease is examined in a review article published in DNA and Cell Biology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the DNA and Cell Biology website until April 13, 2017.
In the article entitled "The Role of Exosomal VP40 in Ebola Virus Disease," Michelle Pleet, Catherine DeMarino, and Fatha Kashanchi, George Mason University, Benjamin Lepene, Ceres Nanosciences, Manassas, VA, and M. Javad Aman, Integrated BioTherapeutics, Gaithersburg, MD, discuss the latest research on the effects of the Ebola VP40 matrix protein on the immune system. The authors suggest that in addition to VP40, additional viral proteins may also be packaged in the membrane-bound exosomal vesicles, intensifying the damaging effects on immune cells.
"Starting in December 2013, Ebola re-emerged in Western Africa and devastated the population of three countries, prompting an international response of physicians and of basic and translational scientists. This epidemic led to the development of new vaccines, therapeutics, and insights into disease pathogenesis and epidemiology," says Carol Shoshkes Reiss, PhD, Editor-in-Chief of DNA and Cell Biology and Professor, Departments of Biology and Neural Science, and Global Public Health at New York University, NY. "This paper from Pleet and colleagues is important because it shows that Ebola-infected cells secrete small bits of cytoplasm inside membranes, which contain Ebola viral proteins that can damage neighboring and distant host cells."
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Research shows how Ebola viral proteins packaged in exosomes affect immune cells - News-Medical.net