#Synthetic Stem Cells Might Eventually Lead to Artificial organs Scientists at the University of Washington (UW) say they have engineered yeast cells (Saccharomyces cerevisiae) that can"talk"to one another,
using the plant hormone auxin. In a paper (ell-cell communication in yeast using auxin biosynthesis
and auxin responsive CRISPR transcription factors published in the American Chemical Society's ACS Synthetic biology journal,
the researchers describe a novel cell-to-cell communication system that enables one yeast cell to regulate the expression of genes and influence the behavior of an entirely separate yeast cell.
It's a basic step in understanding the communication and cooperative processes that might lead to synthetic stem cells that could grow into artificial organs
"said senior author Eric Klavins, Ph d.,a UW associate professor of electrical engineering and of bioengineering. It might also enable engineered yeast to perform complicated behaviors that coordinated multicellular systems such as our immune system can accomplish,
like recognizing an invading pathogen and mounting a response. If so, one might program those cells to collaboratively diagnose the flu or malaria:
just add saliva to a packet of yeast and see if it changes color. For now,
though, the team spearheaded by lead authors Arjun Khakhar, a UW doctoral student in bioengineering, and Nicholas J. Bolten, a UW doctoral student in electrical engineering, simply wanted to see
if it could induce one yeast cell to send a signal that sets off a cascade of changes in another cell.
Let's work together.''But for now it's pretty much'hi.'"'"Synthetic biologists, who assemble genetic parts in new ways with the goal of popping them into an organism to produce reliable behaviors,
have struggled to build modules that enable cell-to-cell communication in organisms that don't naturally do it.
With co-author and UW associate biology professor Jennifer Nemhauser, Ph d, . the UW team figured out how to make a sender yeast cell produce auxin,
a versatile hormone that controls everything from where a plant's roots develop to how effectively they fight off pathogens.
In the receiver yeast cells, the researchers inserted the new transcription factor and engineered it to activate the jellyfish gene that turned the cell green.
When the sender cell released auxin, additional proteins that the researchers introduced in the receiver cell were able to degrade the new transcription factor
and switch off the gene that turned the receiver cell green. That type of simple communication forms the bedrock of multicellular organisms in
such as forming patterns or cooperatively computing basic functions. Since auxin is a plant hormone, mammalian cells also ignore it,
making auxin a potentially useful tool in designing gene therapies or other applications without adverse reactions in humans.
"If you ask someone in computer science what they can do with a programming language, they'll laugh
"If we can figure out the programming language of life, we can do anything that life does, except in a more controllable, reliable way
#Epigenetics Opens Potential Pathway to Treating Glioblastoma Scientists at the University of California, San diego School of medicine and Moores Cancer Center led an international team that discovered that cancer stem cell properties are determined by epigenetic changes.
The study, which was carried out on human tumor samples and mouse models, is published in the Proceedings of the National Academy of Sciences.
The team reports that Lysine-Specific Demethylase 1 (LSD1) turns off genes required to maintain cancer stem cell properties in glioblastoma, a highly aggressive form of brain cancer.
This epigenetic activity helps explain how glioblastoma can resist treatment. In addition drugs that modify LSD1 levels could provide a new approach to treating glioblastoma, according to the researchers.
The investigators first noticed that genetically identical glioblastoma cells isolated from patients differed in their tumorigenicity
This observation suggested that epigenetics, rather than specific DNA sequences, determines tumorigenicity in glioblastoma cancer stem cells."
"One of the most striking findings in our study is that there are dynamic and reversible transitions between tumorigenic
and non-tumorigenic states in glioblastoma that are determined by epigenetic regulation, "said senior author Clark Chen, M d.,Ph d,
. associate professor of neurosurgery and vice-chair of research and academic development at UC San diego School of medicine.
Probing further, Dr. Chen's team discovered that the epigenetic factor determining whether or not glioblastoma cells can proliferate indefinitely as cancer stem cells is their relative abundance of LSD1,
which removes methyl groups from DNA, turning off a number of genes required for maintaining cancer stem cell properties,
including MYC, SOX2, OLIG2 and POU3F2.""This plasticity represents a mechanism by which glioblastoma develops resistance to therapy,"noted Dr. Chen."
"For instance, glioblastomas can escape the killing effects of a drug targeting MYC by simply shutting it off epigenetically
Ultimately, strategies addressing this dynamic interplay will be needed for effective glioblastoma therapy.""Dr. Chen and one of the study's first authors, Jie Li, Ph d.,note that the epigenetic changes driving glioblastoma are similar to those that take place during normal human development."
"Though most cells in our bodies contain identical DNA sequences, epigenetic changes help make a liver cell different from a brain cell,
"said Dr. Li, an assistant project scientist in Chen's lab."Our results indicate that the same programming processes determine
whether a cancer cell can grow indefinitely or not
#DNA"Spare tire"Gets Genome on Road to Repair Certain parts of the genome that are especially vulnerable to damage nonetheless contribute to a crucial,
ubber meets the roadsort of functionalityolecular-level folding that maintains tertiary structures, regulates gene transcription,
How does the genome keep rolling along? It not calling AAA. According to scientists at the University of Utah and the University of Vermont, DNA contains an extra set of guanines,
or G, that function like a spare tire. In fact, this spare can help the genome steer clear of cancer.
Various kinds of damage can happen to DNA, making it unstable, which is a hallmark of cancer.
One common way that our genetic material can be harmed is from a phenomenon called oxidative stress.
When our bodies process certain chemicals or even by simply breathing, one of the products is a form of oxygen that can acutely damage DNA bases,
predominantly the G. In order to stay cancer-free, our bodies must repair this DNA. This is where the special vulnerability noted earlier comes in.
The Utah and Vermont researchers hypothesized that genome instability due to damaged G was counteracted somehow. They scanned the sequences of known human oncogenes associated with cancer,
and found that many contain the four G-stretches necessary for quadruplex formation and a fifth G-stretch one or more bases downstream.
When they exposed these quadruplex-forming sequences to oxidative stress in vitro, a series of different tests indicated that the extra G allowed the damages to fold out from the quadruplex structure,
Role for the Fifth G-Track in G-Quadruplex Forming Oncogene Promoter Sequences during Oxidative Stress:
A fifth G-track found a few nucleotides distant from the G4 tracks involved in folding can act as a pare tire,
and repair of oxidized bases in promoter regions may constitute an additional example of epigenetic modification, in this case of guanine bases,
to regulate gene expression in which the G4 sequences act as sensors of oxidative stress e
#New Cell Structure Finding Might Lead to Novel Cancer Therapies University of Warwick scientists in the U k. say they have discovered a cell structure
which could help researchers understand why some cancers develop. For the first time a structure called'the mesh'has been identified
which helps to hold together cells. They believe their study (he mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle,
which has been published in Life, changes our understanding of the cell's internal scaffolding. The work has implications for researchers'understanding of cancer cells as the mesh is made partly of a protein
which is found to change in certain cancers, such as those of the breast and bladder, according to Stephen Royle, Ph d.,team leader and associate professor and senior Cancer Research UK Fellow at the division of biomedical cell biology at Warwick Medical school."
"As a cell biologist you dream of finding a new structure in cells but it's so unlikely.
Scientists have been looking at cells since the 17th century and so to find something that no one has seen before is said amazing,
"he. Researchers made the discovery by accident while looking at gaps between microtubules which are part of the cells'internal skeleton.
In dividing cells, these gaps are incredibly small at just 25 nanometers (3, 000 times thinner than a human hair.
One of Dr. Royle's Ph d. students was examining mitotic spindles in dividing cells via tomography.
While inter-microtubule bridges in the mitotic spindle had been seen before, the researchers were the first to view the mesh."
"We had been looking in 2d and this gave the impression that'bridges'linked microtubules together,
continued Dr. Royle. his had been known since the 1970s. All of a sudden, tilting the fiber in 3d showed us that the bridges were not single struts at all
but a weblike structure linking all the microtubules together.""The discovery impacts on the research into cancerous cells.
A cell needs to share chromosomes accurately when it divides otherwise the two new cells can end up with the wrong number of chromosomes (aneuploidy)
which has been linked to a range of tumors in different body organs. The mitotic spindle is responsible for sharing the chromosomes
and the researchers at the university believe that the mesh is needed to give structural support.
Too little support from the mesh and the spindle will be too weak to work properly; however too much support will result in it being unable to correct mistakes.
It was found that one of the proteins that make up the mesh, TACC3, is overproduced in certain cancers.
When this situation was mimicked in the lab, the mesh and microtubules were altered and cells had trouble sharing chromosomes during division.
According to Emma Smith, Ph d.,from Cancer Research UK, his early research provides the first glimpse of a structure that helps share out a cell's chromosomes correctly
when it divides, and it might be a crucial insight into why this process becomes faulty in cancer
and whether drugs could be developed to stop it from happening
#Sperm RNA Test May Improve Evaluation of Male Infertility Many couples who struggle with infertility also suffer uncertainty.
even though the American Society for Reproductive Medicine holds that infertility is due in equal measure to male and female factors.
and morphologyre useful mainly for the diagnosis of obvious cases of male infertility. The new test,
in collaboration with scientists from CREATE Fertility Center, University of Toronto, Harvard university, and Georgia Regents University.
The scientific team presented their results July 8 in Science Translational Medicine, in an article entitled,
bsence of sperm RNA elements correlates with idiopathic male infertility. e assessed spermatozoal RNAS from 96 couples presenting with idiopathic infertility
when using assisted reproductive technologies such as in vitro fertilization with or without intracytoplasmic sperm injection. pon validation,
so as to reduce the stress on the couple. About 13%of couples of reproductive age experience fertility problems.
This was confirmed by their diagnosis noted the authors of the Science Translational Medicine article. According to Dr. Krawetz, the diagnostic potential of next-generation sequencing of sperm RNA indicates this method is suited"better to the task"of analyzing the male's role in infertility,
and is a step toward personalized precision reproductive medicine that may help guide the couple to their successful treatment.
Sperm RNA analysis at present is technically challenging, but it is being automated. The technique could become part of a routine examination as"we move toward personalized and precision medicine,"Dr. Krawetz asserted.
While the test is experimental it has the potential for cost savings for both the patients and the healthcare system.
#Dissolvable Microneedles May Herald New Age of Vaccine Delivery Scientists from Osaka University report that flu vaccines delivered using microneedles that dissolve in the skin can protect people against infection even better than the standard needle-delivered vaccine.
The authors of the study (linical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch,
which appears in Biomaterials, say their dissolvable patch could make vaccination easier, safer, and less painful.
According to the World health organization, immunization prevents an estimated 2 million deaths every year. The continued threat of pandemics such as H1n1 swine flu and emerging infectious diseases such as Ebola makes vaccine development and mass vaccination a priority for global healthcare.
Most vaccines are injected under the skin or into the muscle using needles. While this is an effective delivery method,
it requires medical personnel with technical skills and brings the risk of needle-related diseases and injuries.
The new microneedle patch is made of dissolvable material, eliminating needle-related risks. It is also easy to use without the need for trained medical personnel,
making it ideal for use in developing countries, where healthcare resources are limited.""Our novel transcutaneous vaccination using a dissolving microneedle patch is the only application vaccination system that is readily adaptable for widespread practical use,
"said Shinsaku Nakagawa, Ph d.,one of the authors of the paper.""Because the new patch is so easy to use,
we believe it will be particularly effective in supporting vaccination in developing countries.""The new microneedle patch (Microhyala) is dissolvable in water.
The tiny needles are made of hyaluronic acid, a naturally occurring substance that cushions the joints. When the patch is applied like a plaster,
the needles pierce the top layer of skin and dissolve into the body, taking the vaccine with them.
The researchers compared the new system to traditional needle delivery by vaccinating two groups of people against three strains of influenza:
A/H1n1, A/H3n2, and B. None of the subjects had a bad reaction to the vaccine,
showing that it is safe to use in humans. The patch was also effective: people given the vaccine using the microneedles had an immune reaction that was equal to or stronger than those given the vaccine by injection."
"We were excited to see that our new microneedle patch is just as effective as the needle-delivered flu vaccines,
and in some cases even more effective,"said Dr. Nakagawa. Previous research has evaluated the use of microneedles made of silicon or metal,
but they were shown not to be safe. Microneedles made from these materials also run the risk of breaking off in the skin, leaving tiny fragments behind.
The new dissolvable patch eliminates this risk, as the microneedles are designed to dissolve in the skin."
"We have shown that the patch is safe and that it works well. Since it is also painless and very for non-trained people to use,
we think it could bring about a major change in the way we administer vaccines globally, "said Dr. Nakagawa a
#Cell cycle protein Reverses Metabolic Reprogramming of Cancer cells Understanding how cancers cells reprogram cellular metabolic pathways is critical toward the development of novel therapeutic compounds.
Cutting off a cancer cell ood supplyis a veritable lynchpin for the efficient removal of tumors and now researchers at the University of Texas MD Anderson Cancer Center believe they may have found a protein that serves that very function.
and also serve to protect cells from the transformation into tumors.""We know that all cancers grow by learning how to reprogram their metabolism,
"said senior author Mong-Hong Lee, Ph d, . professor of molecular and cellular oncology at MD Anderson Cancer Center. ut exactly how this occurs has not been understood fully.
Our study showed that 14-3-3s opposes and reverses tumor-promoting metabolic programs.""The findings from this study were published recently in Nature Communications through an article entitled ell cycle regulator 14-3-3s opposes
and reverses cancer metabolic reprogramming. 14-3-3s is part of a family of conserved regulatory molecules that are expressed in all eukaryotic cells.
Moreover, the 14-3-3 proteins have been observed to be involved actively in regulating an array of signaling molecules such as kinases, phosphatases,
and transmembrane receptors. 14-3-3s has been shown previously to regulate cancer genes, such as p53 and suppress tumor growth,
but in this instance the investigators were able to observe the protein acting on metabolic pathways
and reversing tumorigenic signals. Dr. Lee and his team showed that 14-3-3s opposed tumor-promoting metabolic programs by increasing the degradation of the transcription factor c-Myc.
Additionally, 14-3-3s demonstrated a suppressive effect on cancer glycolysis, mitochondrial biogenesis, as well as a range of other major metabolic processes of tumors."
"14-3-3s expression levels can help predict overall and recurrence-free survival rates, tumor glucose uptake,
and metabolic gene expression in breast cancer patients,"explained Dr. Lee.""These results highlight that 14-3-3s is an important regulator of tumor metabolism,
and loss of 14-3-3s expression is critical for cancer metabolic reprogramming.""The MD Anderson team is excited about the findings from this new study
and feels that it adds extended insight into the connective pathways between the cell cycle and cancer cell metabolism."
"We anticipate that pharmacologically elevating 14-3-3s's function in tumors could be a promising direction for targeted anticancer metabolism therapy development in the future,"concluded Dr. Lee r
#Plant protein Discovery Opens Door to Better Understanding of Human Gene Silencing Researchers at the Van Andel Research Institute (VARI) published a paper that they say reveals a key molecular mechanism in plants that has significant similarities to certain
signaling mechanisms in humans, which are linked closely to early embryonic development and to diseases such as cancer.
In plants as in animals and humans, intricate molecular networks regulate important biological functions, such as development and stress responses.
The system can be likened to a massive switchboardhen the wrong switches are flipped, genes can be inappropriately turned on or off,
leading to the onset of diseases. Now, VARI scientists report that they have unraveled how a plant protein known as TOPLESS interacts with other molecules responsible for turning genes off.
The findings in plants provide a general model across species for this type of gene silencing,
which is linked to several vital biological functions in humans. The team study (tructural basis for recognition of diverse transcriptional repressors by the TOPLESS family of corepressors appears in Science Advances."
"Using X-ray crystallography, the team determined the three-dimensional structure of TOPLESS, both on its own and when linked with other molecules responsible for turning genes off, thereby regulating gene expression.
Although these interacting molecules were chosen from different signaling pathways in plants, they all linked up with TOPLESS in the same manner"This structure will allow us to take a more targeted approach to investigating TOPLESS's counterparts in humans
"We're extremely excited to continue this work to better understand these proteins and how they interact with other molecules in health and disease states."
"Although the new study provides further insight into human molecular pathways, the work also directly describes how components of the molecular switchboard in plants interact to regulate responses to a multitude of stressors,
including temperature fluctuations. The new findings follow an earlier Nature paper, which was included in the top ten list of scientific breakthroughs of 2009 by Science,
and an earlier Science paper, both of which describe how plants respond to drought and temperature stress.
#Biopharma Demand Is Driving the Cell Culture Market The production of biologic therapies such as vaccines, blood factors,
and are expected to show similar growth in revenues for the next five years. The demand for cell culture and related products is not just rising,
but accelerating, a phenomenon that is reflected in the timing of biopharmaceutical product launches: Since the first biopharmaceutical drug Humulin was launched in 1982 to the beginning of this decade (between 1982 and 2009 27 year period),
there were 117 biopharmaceutical approvals. That an impressive number, but there have been 67 approvals between 2010 and 2014 four year period.
Roughly speaking, biopharmaceutical product launches increased from around 4 to nearly 17 approvals per year. Biopharmaceutical production is increasing not only through the introduction of novel therapeutics,
but also through the introduction of biosimilars or generic biopharmaceuticals, which can be manufactured by several companies.
The market for cell cultures is expected to grow rapidly alongside biopharmaceuticals and with significant evolution in culture technology.
Cell Line Trends Many biopharmaceuticals are produced by bacteria especially the species Escherichia coli and Bacillus subtilis. E coli has been studied in microbiology laboratories for many years
and was the first organism to have its entire genome mapped. It is inexpensive to cultivate,
it replicates quickly, and it serves as a good model organismhat is, it provides an example of how other similar life forms will behaveuch as how they grow
and reproduce, and what makes them deteriorate or die. Bacterial culture is the workhorse of the biotechnology industry.
Animal cells are much more fragile than yeast and bacterial cells. They are often much larger than microorganisms
and live in a collective as part of organs or tissues within complex anatomical systems. Animal cells are held together by a delicate membrane
thus, it is more expensive than traditional fermentation. The most widely used animal cells are Chinese hamster ovary (CHO) cells.
The rising stakes and production levels of companies active in biopharmaceuticals have dictated improved reproducibility or consistency in product;
The biopharmaceutical industry shift away from animal-derived culture products is expected to continue, particularly given the ascension of mammalian cell lines in biopharmaceutical production.
Serum-free media is the more complex composition designed for universal use in culturing mammalian cell lines.
Working and Master Cell Banks Once a biopharmaceutical company obtains a beginning cell bank from a cell culture collection,
the company scientists will do the work of genetically engineering those cells for particular uses.
This work may involve various changes such as gene amplification or gene duplication, the addition of one or more copies of a gene of interest so that each cell produces more protein.
Genetic engineering may also be used to alter an animal cell line preferred growing conditions. For example, an animal cell line that naturally prefers to grow attached to a surface can be adapted to grow suspended in liquid,
a master cell bank is created. It will be maintained as the source of all cells used to produce the company drug through preclinical and clinical testing and then into commercial sale.
Working cell banks are created from the master cell bank for producing batches of product. Each batch will be made by seed stock that came from either another working cell bank or the master cell bank.
Fermentation Requirements A complex set of conditions that affect cell propagation, product yield, and concentration of nutrients, waste,
and products must be considered in designing a fermentation process. Of paramount concern are fluid viscosity
momentum, and the sizes of the cells involved. The performance of a fermentor or bioreactor is governed by thermodynamics (such as the solubility of oxygen in the medium), microkinetics (such as cell growth and product formation),
and transport of materials (moving nutrients into the cells and removing waste products). Optimal mixing ensures effective oxygen transfer, heat transfer,
and dispersal of materials. Minor deficiencies in circulation of the medium can have major effects on growth and protein production.
Shifts in Productive Capacity Cell culture production is growing faster in the Asia Pacific region than any place else in the world.
in particular single-use disposable production systems, are dramatically lowering building costs of biomanufacturing plants. In the near term
In the longer term, biomanufacturing expansion will extend into South america, Eastern europe, and Africa. Market Drivers An important driver of the cell culture market is the production of seasonal influenza vaccines,
as well as pandemic vaccine candidates. Seasonal influenza vaccines have traditionally been produced using egg-based technology. However, this labor-intensive approach to vaccine development is currently being replaced by cell-culture systems.
Prefluce, the first cell culture-based vaccine, received European approval in March 2011 and was available for the 2011012 influenza season in the 13 participating European union countries.
On November 20 2012, the U s. Food and Drug Administration approved the use of Flucelvax, which is the first U s.-licensed (trivalent inactivated) influenza vaccine manufactured using cell culture technology.
Stem cell research will also add to the robust growth of the cell culture market. The growing use
and diverse applications of stem cells are having a significant impact on the media market,
as companies work to understand how best to optimize their growth. For stem cell applications, serum-free media that lack growth factors, cytokines,
#First Artificial Ribosome Designed Scientists at the University of Illinois at Chicago and Northwestern University say they have engineered a tethered ribosome that works nearly as well as the authentic organelle that produces all the proteins and enzymes within the cell.
The engineered ribosome may enable the production of new drugs and next-generation biomaterials and lead to a better understanding of how ribosomes function, according to the researchers.
The artificial ribosome, called Ribo-T, was created in the laboratories of Alexander Mankin, Ph d.,director of the UIC College of Pharmacy's Center for Biomolecular Sciences
and Northwestern's Michael Jewett, Ph d.,assistant professor of chemical and biological engineering. The human-made ribosome may be able to be manipulated in the laboratory to do things natural ribosomes cannot do.
Ribo-T may be able to be tuned to produce unique and functional polymers for exploring ribosome functions
or producing designer therapeutics, and perhaps one day even non-biological polymers, point out Dr. Mankin."
"We felt like there was a very small chance Ribo-T could work, but we did not really know,
"he noted. Dr. Mankin said he and Dr. Jewett and their colleagues were frustrated in their investigations by the ribosomes'subunits falling apart
"Our new protein-making factory holds promise to expand the genetic code in a unique and transformative way, providing exciting opportunities for synthetic biology and biomolecular engineering."
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