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First time ever: Researchers rewrite an entire bacterial genome and add a healthy twist

First time ever: Researchers rewrite an entire bacterial genome and add a healthy twist | Systems biology and bioinformatics | Scoop.it

Scientists from Yale and Harvard have recoded the entire genome of an organism and improved a bacterium’s ability to resist viruses, a dramatic demonstration of the potential of rewriting an organism’s genetic code.

“This is the first time the genetic code has been fundamentally changed,” said Farren Isaacs, assistant professor of molecular, cellular, and developmental biology at Yale and co-senior author of the research published Oct. 18 in the journal Science. “Creating an organism with a new genetic code has allowed us to expand the scope of biological function in a number of powerful ways.”

 

The creation of a genomically recoded organism raises the possibility that researchers might be able to retool nature and create potent new forms of proteins to accomplish a myriad purposes — from combating disease to generating new classes of materials.

 

The research — headed by Isaacs and co-author George Church of Harvard Medical School — is a product of years of studies in the emerging field of synthetic biology, which seeks to re-design natural biological systems for useful purposes.

 

In this case, the researchers changed fundamental rules of biology.

Proteins, which are encoded by DNA’s instructional manual and are made up of 20 amino acids, carry out many important functional roles in the cell. Amino acids are encoded by the full set of 64 triplet combinations of the four nucleic acids that comprise the backbone of DNA. These triplets (sets of three nucleotides) are called codons and are the genetic alphabet of life.

 

Isaacs, Jesse Rinehart of Yale, and the Harvard researchers explored whether they could expand upon nature’s handywork by substituting different codons or letters throughout the genome and then reintroducing entirely new letters to create amino acids not found in nature. This work marks the first time that the genetic code has been completely changed across an organism’s genome.

 

In the new study, the researchers working with E. coli swapped a codon and eliminated its natural stop sign that terminates protein production. The new genome enabled the bacteria to resist viral infection by limiting production of natural proteins used by viruses to infect cells. Isaacs — working with Marc Lajoie of Harvard, Alexis Rovner of Yale, and colleagues — then converted the “stop” codon into one that encodes new amino acids and inserted it into the genome in a plug-and-play fashion. 

 

The work now sets the stage to convert the recoded bacterium into a living foundry, capable of biomanufacturing new classes of  “exotic” proteins and polymers. These new molecules could lay the foundation for a new generation of materials, nanostructures, therapeutics, and drug delivery vehicles, Isaacs said.

 

“Since the genetic code is universal, it raises the prospect of recoding genomes of other organisms,” Isaacs said. “This has tremendous implications in the biotechnology industry and could open entirely new avenues of research and applications.”


Via Dr. Stefan Gruenwald
Dmitry Alexeev's insight:

thats a new generation biological tool although there has been already attempts to encode non-standard amino acids - but never before on a full genome scale - intrestingle how soon wilkl this be available as a conventional instrument? this is a novel scientific tool - which will among others help us to study life

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odysseas spyroglou's curator insight, October 19, 2013 8:46 AM

The brave new world starts here. I hope we'll find our way to a less dystopian future.

Leire Tapia's curator insight, October 21, 2013 4:08 PM

He elegido esta noticia porque la relaciono con la libertad de investigación. Es un derecho vinculado al ser humano y es un derecho exigible. Es también importante comunicar los resultados y no caer en el peligro de la censura. No hay que esconder lo que la ciencia descubre pero si es importante establecer límites relacionados con la protección de la salud y con la dignidad humana.

Systems biology and bioinformatics
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Huang and Boushey provide their... - Journal of Allergy and Clinical Immunology | Facebook

Huang and Boushey provide their perspective on the findings of studies of differences in the airway microbiome in patients with asthma vs. healthy...
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Microbiomes of lungs
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Squid uses luminescent bacteria to match moonlight welling down from above to cancel out its own shadow

Squid uses luminescent bacteria to match moonlight welling down from above to cancel out its own shadow | Systems biology and bioinformatics | Scoop.it

The aquarium looks empty, but there is something in it. A pair of eyes stick out from the sandy floor, and their owner is easily scooped up into a glass bowl. At first, the creature looks like a hazelnut truffle — small, round and covered in tiny flecks. But with a gentle shake, the flecks of sand fall off to reveal a female Hawaiian bobtail squid (Euprymna scolopes), about the size of a thumb. As she jets furiously around the bowl, discs of pigment bloom and fade over her skin like a living pointillist painting.


There are no other animals in the bowl, but the squid is not alone. Its undersides contain a two-chambered light organ that is full of glowing bacteria called Vibrio fischeri. In the wild, their luminescence is thought to match the moonlight welling down from above and cancel out the squid's shadow, hiding the animal from predators. From below, the squid is invisible. From above, it is adorable. “They're just so beautiful,” says Margaret McFall-Ngai, a zoologist at the University of Wisconsin–Madison. “They're phenomenal lab animals.”


Few things excite McFall-Ngai more than the partnership between the bobtail squid and V. fischeri — and that is after studying it for more than 26 years. Over that time, she has shown that this symbiotic relationship is more intimate than anyone had imagined. She has found that the bacterium out-competes other microbes to establish an entirely faithful relationship with one host. It interacts with the squid's immune system, guides its body clock and shapes its early development by transforming its body.




Via Dr. Stefan Gruenwald
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cast no shadow

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Blood Work: Scientists Uncover Surprising New Tools to Rejuvenate the Brain | ucsf.edu

Blood Work: Scientists Uncover Surprising New Tools to Rejuvenate the Brain | ucsf.edu | Systems biology and bioinformatics | Scoop.it
Dmitry Alexeev's insight:

its none systems biology non bioinformatics... yet)

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Enrichment Map: A Network-Based Method for Gene-Set Enrichment Visualization and Interpretation

PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.
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looks amazing on our data

 

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Diet and Feeding Pattern Affect the Diurnal Dynamics of the Gut Microbiome

Diet and Feeding Pattern Affect the Diurnal Dynamics of the Gut Microbiome | Systems biology and bioinformatics | Scoop.it
eding/fasting cycle influence host metabolism and contribute to obesity and metabolic diseases. However, fundamental characteristics of this relationship between the feeding/fasting cycle and the gut microbiome are unknown. Our studies show that the gut microbiome is highly dynamic, exhibiting daily cyclical fluctuations in composition. Diet-induced obesity dampens the daily feeding/fasting rhythm and diminishes many of these cyclical fluctuations. Time-restricted feeding (TRF), in which feeding is consolidated to the nocturnal phase, partially restores these cyclical fluctuations. Furthermore, TRF, which protects against obesity and metabolic diseases, affects bacteria shown to influence host metabolism. Cyclical changes in the gut microbiome from feeding/fasting rhythms contribute to the diversity of gut microflora and likely represent a mechanism by which the gut microbiome affects host metabolism. Thus, feeding pattern and time of harvest, in addition to diet, are important parameters when assessing the microbiome’s contribution to host metabolism.
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fasting and microbiome dynamics

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Potential of fecal microbiota for early-stage detection of colorectal cancer - Zeller - 2014 - Molecular Systems Biology - Wiley Online Library

Potential of fecal microbiota for early-stage detection of colorectal cancer - Zeller - 2014 - Molecular Systems Biology - Wiley Online Library | Systems biology and bioinformatics | Scoop.it
Dmitry Alexeev's insight:

not that systematic - but the point is 20 per cent more sensitivity

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SciCurve - Understand your Field of Research.

SciCurve - Understand your Field of Research. | Systems biology and bioinformatics | Scoop.it
Dmitry Alexeev's insight:

exactly what I was looking for today - graphs of keyword publishsing and citing

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Kinetic competition during the transcription cycle results in stochastic RNA processing. - Abstract - Europe PubMed Central

Abstract: Synthesis of mRNA in eukaryotes involves the coordinated action of many enzymatic processes, including initiation, elongation, splicing and...
Dmitry Alexeev's insight:

looks just amazing how they can totally measure all the processes in one gene

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Genome Medicine | Abstract | Modules, networks and systems medicine for understanding disease and aiding diagnosis

Genome Medicine | Abstract | Modules, networks and systems medicine for understanding disease and aiding diagnosis | Systems biology and bioinformatics | Scoop.it
Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.
Dmitry Alexeev's insight:

systems medicine in translation

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Rethinking “Enterotypes”

Rethinking “Enterotypes” | Systems biology and bioinformatics | Scoop.it
Dmitry Alexeev's insight:

Took Rob Knight a while to publish work 

we ssaw it in 2012 in Paris

http://www.cell.com/cell-host-microbe/pdfExtended/S1931-3128(14)00346-1 - here is full version

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Games of life and death: antibiotic resistance and production through the lens of evolutionary game theory

Games of life and death: antibiotic resistance and production through the lens of evolutionary game theory | Systems biology and bioinformatics | Scoop.it
Dmitry Alexeev's insight:

did not read it through yet - seems intresting

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repubHub | iCopyright.com

repubHub | iCopyright.com | Systems biology and bioinformatics | Scoop.it
repubHub: Where editors, bloggers and marketers get licensed, republishable content.
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ots of samples in big data application

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Integrative Systems Approaches to Network Modeling of Biological Processes

Integrative Systems Approaches to Network Modeling of Biological Processes | Systems biology and bioinformatics | Scoop.it
Professor of Computational Biology and Bioinformatics, Department of Biostatistics, Harvard University, Dana-Farber Cancer Institute (Watch Webinar "Integrative Systems Approaches to Network Modeling of Biological Processes" by John Quackenbush,...
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well a prominent professor and comprehensive seminar

 

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A disease module in the interactome explains disease heterogeneity, drug response and captures novel pathways and genes

A disease module in the interactome explains disease heterogeneity, drug response and captures novel pathways and genes | Systems biology and bioinformatics | Scoop.it
Dmitry Alexeev's insight:

network science allows for new approaches to disease analysis

 

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Studies on Modulation of Gut Microbiota by Wine Polyphenols: From Isolated Cultures to Omic Approaches

Studies on Modulation of Gut Microbiota by Wine Polyphenols: From Isolated Cultures to Omic Approaches | Systems biology and bioinformatics | Scoop.it
Moderate consumption of wine seems to produce positive health effects derived from the occurrence of bioactive polyphenols. The gut microbiota is involved in the metabolism of phenolic compounds, and these compounds and/or their metabolites may modulate gut microbiota through the stimulation of the growth of beneficial bacteria and the inhibition of pathogenic bacteria. The characterization of bacterial metabolites derived from polyphenols is essential in order to understand their effects, inclu
Dmitry Alexeev's insight:

we just like wine and microbiota)

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A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping: Cell

A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping: Cell | Systems biology and bioinformatics | Scoop.it
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holy crap)

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Ben Althouse on Diseases as Complex Systems

Ben Althouse on Diseases as Complex Systems | Systems biology and bioinformatics | Scoop.it

щлThis is the first in a series of interviews highlighting the work of experts in the field of complex systems science. Dr. Ben Althouse, an Omidyar Fellow at the Santa Fe Institute, is a mathematical epidemiologist focusing on the dynamics of infectious disease transmission. Ben holds both an ScM in Biostatistics and a PhD in Epidemiology from the Johns Hopkins Bloomberg School of Public Health where he focused on understanding Dengue fever and other sylvatic mosquito-borne viruses (arboviruses) in Senegal using mechanistic modeling and the SIR model. Dr. Althouse also attended the Santa Fe Institute’s Complex Systems Summer School during his graduate studies.


Via Jorge Louçã
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An enteric virus can replace the beneficial function of commensal bacteria : Nature : Nature Publishing Group

An enteric virus can replace the beneficial function of commensal bacteria : Nature : Nature Publishing Group | Systems biology and bioinformatics | Scoop.it
Intestinal microbial communities have profound effects on host physiology. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined. Here we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Murine norovirus (MNV) infection of germ-free or antibiotic-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signalling. Consistent with this observation, the IFN-[agr] receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of treatment with antibiotics in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity, similarly to commensal bacteria.
Dmitry Alexeev's insight:

viral

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The metacommunity concept: a framework for multi-scale community ecology - Leibold - 2004 - Ecology Letters - Wiley Online Library

The metacommunity concept: a framework for multi-scale community ecology - Leibold - 2004 - Ecology Letters - Wiley Online Library | Systems biology and bioinformatics | Scoop.it
Dmitry Alexeev's insight:

we are quite excited about meta-community inside meta-community theory application to viruses living in bacteria living in human

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There Is No ‘Healthy’ Microbiome

There Is No ‘Healthy’ Microbiome | Systems biology and bioinformatics | Scoop.it

IN the late 17th century, the Dutch naturalist Anton van Leeuwenhoek looked at his own dental plaque through a microscope and saw a world of tiny cells “very prettily a-moving.” He could not have predicted that a few centuries later, the trillions of microbes that share our lives — collectively known as the microbiome — would rank among the hottest areas of biology.

These microscopic partners help us by digesting our food, training our immune systems and crowding out other harmful microbes that could cause disease. In return, everything from the food we eat to the medicines we take can shape our microbial communities — with important implications for our health. Studies have found that changes in our microbiome accompany medical problems from obesity to diabetes to colon cancer.


Via Complexity Digest
Dmitry Alexeev's insight:

Our microbes are truly part of us, and just as we are vast in our variety, so, too, are they. We must embrace this complexity if we hope to benefit from it.

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Rowan Norrie's curator insight, November 10, 2014 6:14 AM

The fascinating world of the microbiome and the opportunities it heralds for future medicine

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Biogeography and individuality shape function in the human skin metagenome : Nature : Nature Publishing Group

Biogeography and individuality shape function in the human skin metagenome : Nature : Nature Publishing Group | Systems biology and bioinformatics | Scoop.it
Dmitry Alexeev's insight:

biogeography and reference free

 

we are getting deeper

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Abstract LB-155: Ovarian cancer-induced changes in the intestinal microbiota as potential biomarkers for early detection

Dmitry Alexeev's insight:

i actually doubt that microbiota can be a distinctive marker - unless we programm it

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Gut microbes and adverse food reactions: Focus on gluten related disorders

Gut microbes and adverse food reactions: Focus on gluten related disorders | Systems biology and bioinformatics | Scoop.it
Immediately following birth, the gastrointestinal tract is colonized with a complex community of bacteria, which helps shape the immune system. Under conditions of health, the immune system is able to differentiate between innocuous antigens, including food protein and commensals, and harmful antigens such as pathogens. However, patients with celiac disease (CD) develop an intolerance to gluten proteins which results in a pro-inflammatory T-cell mediated immune response with production of anti-g
Dmitry Alexeev's insight:

celiac disease summary - all concearning biota

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Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity

Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity | Systems biology and bioinformatics | Scoop.it
Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut–brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.
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