Wednesday, October 30, 2013

Why Plants Usually Live Longer Than Animals

Stem cells are crucial for the continuous generation of new cells. Although the importance of stem cells in fuelling plant growth and development still many questions on their tight molecular control remain unanswered. Plant researchers at VIB and Ghent University discovered a new step in the complex regulation of stem cells.

 A root tip of the model plant Arabidopsis thaliana. The organizing cells are visualized by the green fluorescence and are surrounded by the stem cells (within the white frame). (Credit: © VIB, 2013)

Today, their results are published online in this week's issue of Science Express.
Lieven De Veylder said, "Our data suggest that certain organizing stem cells in plant roots are less sensitive for DNA-damage. Those cells hold an original and intact DNA copy which can be used to replace damaged cells if necessary. Animals rely on a similar mechanism but most likely plants have employed this in a more optimized manner. This could explain why many plants can live for more than hundreds of years, while this is quite exceptional for animals."
Quiescent organisers of plant growth
Plant growth and development depend on the continuous generation of new cells. A small group of specialized cells present in the growth axes of a plant is driving this. These so-called stem cells divide at a high frequency and have the unique characteristic that the original mother cell keeps the stem cell activity while the daughter cell acquires a certain specialization. Besides these stem cells, plant roots also harbor organizing cells. These organizing cells divide with a three- to ten-fold lower frequency, therefore often referred to as quiescent center cells. The organizing cells control the action of the surrounding stem cells and can replace them if necessary.
A new molecular network
For almost 20 years, scientists all over the world have been studying the action of the stem cells and that of their controlling organizing cells. Until now it was not known how quiescent and actively dividing cells could co-exist so closely and which mechanisms are at the basis of the quiescent character. Plant researchers at VIB and Ghent University have now identified a new molecular network that increases our understanding of stem cell regulation and activity.
Central in this process is the discovery of a new protein, the ERF115 transcription factor. The scientists demonstrated that the organizing cells barely divide because of the inhibition of ERF115 activity. When the organizing cells need to divide to replace damaged surrounding stem cells, ERF115 gets activated. ERF115 then stimulates the production of the plant hormone phytosulfokine which in turn activates the division of the organizing cells. Thus, the ERF115-phytosulfokine network acts as a back-up system during stress conditions which are detrimental for the activity of stem cells.
 
Journal Reference:
  1. Jefri Heyman, Toon Cools, Filip Vandenbussche, Ken S. Heyndrickx, Jelle Van Leene, Ilse Vercauteren, Sandy Vanderauwera, Klaas Vandepoele, Geert De Jaeger, Dominique Van Der Straeten, and Lieven De Veylder. ERF115 Controls Root Quiescent Center Cell Division and Stem Cell Replenishment. Science, 24 October 2013 DOI: 10.1126/science.1240667
Courtesy: ScienceDaily

 

Monday, October 28, 2013

Making Hydrogen Cheaply by Imitating Bacteria? Unique Chemistry in Hydrogen Catalysts Revealed

Making hydrogen easily and cheaply is a dream goal for clean, sustainable energy. Bacteria have been doing exactly that for billions of years, and now chemists at the University of California, Davis, and Stanford University are revealing how they do it, and perhaps opening ways to imitate them.'

This hydrogen-generating cluster of iron (brown) and sulfur (yellow) atoms, with side groups of carbon monoxide (gray/red) and cyanide (gray/blue), could be a key to future fuel sources. (Credit: Protein Data Bank/courtesy graphic)

A study published Oct. 25 in the journal Science describes a key step in assembling the hydrogen-generating catalyst.
"It's pretty interesting that bacteria can do this," said David Britt, professor of chemistry at UC Davis and co-author on the paper. "We want to know how nature builds these catalysts -- from a chemist's perspective, these are really strange things."
The bacterial catalysts are based on precisely organized clusters of iron and sulfur atoms, with side groups of cyanide and carbon monoxide. Those molecules are highly toxic unless properly controlled, Britt noted.
The cyanide and carbon monoxide groups were known to come from the amino acid tyrosine, Britt said. Jon Kuchenreuther, a postdoctoral researcher in Britt's laboratory, used a technique called electron paramagnetic resonance to study the structure of the intermediate steps.
They found a series of chemical reactions involving a type of highly reactive enzyme called a radical SAM enzyme. The tyrosine is attached to a cluster of four iron atoms and four sulfur atoms, then cut loose leaving the cyanide and carbon monoxide groups behind.
"People think of radicals as dangerous, but this enzyme directs the radical chemistry, along with the production of normally poisonous CO and CN, along safe and productive pathways," Britt said.
Kuchenreuther, Britt and colleagues also used another technique, Fourier Transform Infrared to study how the iron-cyanide-carbon monoxide complex is formed. That work will be published separately.
"Together, these results show how to make this interesting two-cluster enzyme," Britt said. "This is unique, new chemistry."
Britt's laboratory houses the California Electron Paramagnetic Resonance center (CalEPR), the largest center of its kind on the west coast.
Other authors on the paper are: at UC Davis, postdoctoral researchers William Myers and Troy Stich, project scientist Simon George and graduate student Yaser NejatyJahromy; and at Stanford University, James Swartz, professor of chemical engineering and bioengineering. The work was supported by grants from the U.S. Department of Energy.
 
Journal Reference:
  1. J. M. Kuchenreuther, W. K. Myers, T. A. Stich, S. J. George, Y. NejatyJahromy, J. R. Swartz, R. D. Britt. A Radical Intermediate in Tyrosine Scission to the CO and CN- Ligands of FeFe Hydrogenase. Science, 2013; 342 (6157): 472 DOI: 10.1126/science.1241859

Courtesy: ScienceDaily
 

Saturday, October 26, 2013

Need Different Types of Tissue? Just Print Them!

What sounds like a dream of the future has already been the subject of research for a few years: simply printing out tissue and organs. Now scientists have further refined the technology and are able to produce various tissue types.

In the lab instead of at the office: researchers using inkjet printers to print cell suspensions onto shimmering pink hydrogel pads, which prevent desiccation. (Credit: © Fraunhofer IGB)

The recent organ transplant scandals have only made the problem worse. According to the German Organ Transplantation Foundation (DSO), the number of organ donors in the first half of 2013 has declined more than 18 percent in comparison to the same period the previous year. At the same time, one can assume that the demand in the next years will continuously rise, because we continue to age and field of transplantation medicine is continuously advancing. Many critical illnesses can already be successfully treated today by replacing cells, tissue, or organs. Government, industry, and the research establishment have therefore been working hard for some time to improve methods and procedures for artificially producing tissue. This is how the gap in supply is supposed to be closed.
Bio-ink made from living cells
One technology might assume a decisive role in this effort, one that we are all familiar with from the office, and that most of us would certainly not immediately connect with the production of artificial tissue: the inkjet printer. Scientists of the Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) in Stuttgart have succeeded in deve- loping suitable bio-inks for this printing technology. The transparent liquids consist of components from the natural tissue matrix and living cells. The substance is based on a well known biological material: gelatin. Gelatin is derived from collagen, the main constituent of native tissue. The researchers have chemically modified the gelling behavior of the gelatin to adapt the biological molecules for printing. Instead of gelling like unmodified gelatin, the bio-inks remain fluid during printing. Only after they are irradiated with UV light, they crosslink and cure to form hydrogels. These are polymers containing a huge amount of water (just like native tissue), but which are stable in aqueous environments and when being warmed up to physiological 37°C. The researchers can control the chemical modification of the biological molecules so that the resulting gels have differing strengths and swelling characteristics. The properties of natural tissue can therefore be imitated -- from solid cartilage to soft adipose tissue.
In Stuttgart synthetic raw materials are printed as well that can serve as substitutes for the extracellular matrix. For example a system that cures to a hydrogel devoid of by-products, and can be immediately populated with genuine cells. "We are concentrating at the moment on the 'natural' variant. That way we remain very close to the original material. Even if the potential for synthetic hydrogels is big, we still need to learn a fair amount about the interactions between the artificial substances and cells or natural tissue. Our biomolecule-based variants provide the cells with a natural environment instead, and therefore can promote the self-organizing behavior of the printed cells to form a functional tissue model," explains Dr. Kirsten Borchers in describing the approach at IGB.
The printers at the labs in Stuttgart have a lot in common with conventional office printers: the ink reservoirs and jets are all the same. The differences are discovered only under close inspection. For example, the heater on the ink container with which the right temperature of the bio-inks is set. The number of jets and tanks is smaller than in the office counterpart as well. "We would like to increase the number of these in cooperation with industry and other Fraunhofer Institutes in order to simultaneously print using various inks with different cells and matrices. This way we can come closer to replicating complex structures and different types of tissue," says Borchers.
The big challenge at the moment is to produce vascularized tissue. This means tissue that has its own system of blood vessels through which the tissue can be provided with nutrients. IGB is working on this jointly with other partners under Project ArtiVasc 3D, supported by the European Union. The core of this project is a technology platform to generate fine blood vessels from synthetic materials and thereby create for the first time artificial skin with its subcutaneous adipose tissue. "This step is very important for printing tissue or entire organs in the future. Only once we are successful in producing tissue that can be nourished through a system of blood vessels can printing larger tissue structures become feasible," says Borchers in closing. She will be exhibiting the IGB bioinks at Biotechnica in Hanover, 8-10 October 2013 (Hall 9, Booth E09).
 
Story Source:
The above story is based on materials provided by Fraunhofer-Gesellschaft.

Courtesy: ScienceDaily
 

Saturday, October 19, 2013

Cell Growth Discovery Has Implications for Targeting Cancer

The way cells divide to form new cells -- to support growth, to repair damaged tissues, or simply to maintain our healthy adult functioning -- is controlled in previously unsuspected ways UC San Francisco researchers have discovered. The findings, they said, may lead to new ways to fight cancer.
 
UCSF researchers have discovered that production of proteins (balls) that work together as molecular machines to perform key functions for the cell at particular phases of cell division — G1 (gray), S (blue) and mitosis (green) — is ramped up and down in a coordinated way, regulated by translation of a gene’s messenger RNA into the amino acid building blocks of protein. Distances between proteins represents how closely their production is regulated together at this translational level. (Credit: UCSF)

The steps leading a quiet cell to make and divvy up new parts to form daughter cells rely on some of the cell's most complex molecular machines. Different machines play key roles at different stages of this cell cycle. Each of these cellular machines consists of many proteins assembled into a functioning whole. They carry out such tasks as repairing DNA in the newly replicated gene-bearing chromosomes, for instance, or helping pull the chromosomes apart so that they can be allocated to daughter cells.
In a study published online on October 10, 2013 in the journal Molecular Cell, UCSF researchers led by molecular biologist Davide Ruggero, PhD, associate professor of urology, and computational biologist Barry Taylor, PhD, assistant professor of epidemiology and biostatistics, found that the production of entire sets of proteins that work together to perform such crucial tasks is ramped up together, all at once -- not due to the transcription of genes into messenger RNA, a phenomenon scientists often study to sort out cellular controls -- but at a later stage of gene expression that occurs within the cell's protein-making factories, called ribosomes.
"We have found that these proteins are regulated specifically and exquisitely during the cell cycle," Ruggero said. When this regulation falters, it wreaks havoc in the cell, he added. "Cell-cycle control is a process that is most often misregulated in human disease," he said.
More specifically, the researchers found that this coordinated timing of protein production during the cell cycle is largely governed at the tail end of gene expression, within the ribosome, where cellular machinery acts on messenger RNA to churn out the chains of amino acids that eventually fold into functional form as proteins.
In 2010 Ruggero reported key evidence suggesting that this stage of protein production, called "translation," might be an often-neglected process in many tumors, ranging from lymphomas, multiple myeloma and prostate cancer.
In the new study, the researchers examined translation of messenger RNA into protein at the classic phases of the cell cycle, before the cell actually divides. These are the G1 phase, when cells grow and make lots of proteins before replicating their DNA; the S phase, when cells replicate their DNA; and the G2 phase, when cells make internal components known as organelles, which they divvy up along with the chromosomes when the cell actually divides during mitosis.
The scientists used a technique know as ribosome profiling, originally developed for yeast cells in the lab of Jonathan Weismann, PhD, Howard Hughes Investigator at UCSF and professor of cellular and molecular pharmacology, to figure out which messenger RNA was being translated into protein by the ribosome during human cell division. They then used computational techniques developed by Taylor's lab team along with the lab team of Adam Olshen, PhD, professor of epidemiology and biostatistics, to better quantify which genes had been translated into proteins.
By conducting a genome-wide investigation of translation and interrogating the data with sophisticated computer algorithms, the researchers discovered that different groups of protein were made in abundance at a particular phase, only to be quieted during another phase of the cell cycle. Previous studies of translation of messenger RNA into protein focused on only one or just a few genes at a time, according to Ruggero and Taylor.
"We hope these methods will be helpful to others who study gene regulation at the translational stage in various diseases, and those who want to identify specific targets for drug development based on discoveries of aberrant translation," Taylor said.
Ruggero has been a pioneer in probing the ability of tumor cells to make extraordinary amounts of protein to sustain their rapid growth and immortality. He also is exploring ways to therapeutically target this excess protein production in cancer.
One striking finding from this new UCSF study is the discovery that production of a protein called RICTOR is boosted due to increased translation during the S phase of the cell cycle. RICTOR serves as a signal to help the cell cycle run like finely tuned clockwork, but several studies suggest that RICTOR often is constitutively turned on in cancer, Ruggero said.
The biochemical signaling cascade within the cell that RICTOR is a part of is under extensive investigation for experimental cancer therapies, and these new findings may point to novel strategies for drug development Ruggero said. Ruggero and Craig Stumpf, PhD, a postdoctoral fellow with his lab and the first author of the Molecular Cell paper, now are tracking down the upstream trigger that coordinates timing of many of the other suites of proteins that are produced simultaneously during the different cell-cycle phases.
 
Journal Reference:
  1. Craig R. Stumpf, Melissa V. Moreno, Adam B. Olshen, Barry S. Taylor, Davide Ruggero. The Translational Landscape of the Mammalian Cell Cycle. Molecular Cell, 2013; DOI: 10.1016/j.molcel.2013.09.018
Courtesy: ScienceDaily
 

Thursday, October 17, 2013

Pandoravirus: Missing Link Discovered Between Viruses and Cells

With the discovery of Mimivirus ten years ago and, more recently, Megavirus chilensis[1], researchers thought they had reached the farthest corners of the viral world in terms of size and genetic complexity. With a diameter in the region of a micrometer and a genome incorporating more than 1,100 genes, these giant viruses, which infect amoebas of the Acanthamoeba genus, had already largely encroached on areas previously thought to be the exclusive domain of bacteria. For the sake of comparison, common viruses such as the influenza or AIDS viruses only contain around ten genes each.
 
 .2 µm Pandoravirus salinus observed under the electron microscope. (Credit: © IGS CNRS-AMU)

In the article published in Science, the researchers announced they had discovered two new giant viruses:
  • Pandoravirus salinus, on the coast of Chile;
  • Pandoravirus dulcis, in a freshwater pond in Melbourne, Australia.
Detailed analysis has shown that these first two Pandoraviruses have virtually nothing in common with previously characterized giant viruses. What's more, only a very small percentage (6%) of proteins encoded by Pandoravirus salinus are similar to those already identified in other viruses or cellular organisms. With a genome of this size, Pandoravirus salinus has just demonstrated that viruses can be more complex than some eukaryotic cells[2]. Another unusual feature of Pandoraviruses is that they have no gene allowing them to build a protein like the capsid protein, which is the basic building block of traditional viruses.
Despite all these novel properties, Pandoraviruses display the essential characteristics of other viruses in that they contain no ribosome, produce no energy and do not divide.
This groundbreaking research included an analysis of the Pandoravirus salinus proteome, which proved that the proteins making it up are consistent with those predicted by the virus' genome sequence. Pandoraviruses thus use the universal genetic code shared by all living organisms on the planet.
This shows just how much more there is to learn regarding microscopic biodiversity as soon as new environments are considered. The simultaneous discovery of two specimens of this new virus family in sediments located 15,000 km apart indicates that Pandoraviruses, which were completely unknown until now, are very likely not rare.
It definitively bridges the gap between viruses and cells -- a gap that was proclaimed as dogma at the very outset of modern virology back in the 1950s.
It also suggests that cell life could have emerged with a far greater variety of pre-cellular forms than those conventionally considered, as the new giant virus has almost no equivalent among the three recognized domains of cellular life, namely eukaryota (or eukaryotes), eubacteria, and archaea.
Notes
[1] Arslan D, Legendre M, Seltzer V, Abergel C, Claverie JM (2011) "Distant Mimivirus relative with a larger genome highlights the fundamental features of Megaviridae." PNAS. 108:17486-91
[2] Parasitic microsporidia of the Encephalitozoon genus in particular.
 
Journal Reference:
  1. N. Philippe, M. Legendre, G. Doutre, Y. Coute, O. Poirot, M. Lescot, D. Arslan, V. Seltzer, L. Bertaux, C. Bruley, J. Garin, J.-M. Claverie, C. Abergel. Pandoraviruses: Amoeba Viruses with Genomes Up to 2.5 Mb Reaching That of Parasitic Eukaryotes. Science, 2013; 341 (6143): 281 DOI: 10.1126/science.1239181 
Courtesy: ScienceDaily

Tuesday, October 15, 2013

New 3-D Method Used to Grow Miniature Pancreas

An international team of researchers from the University of Copenhagen has successfully developed an innovative 3D method to grow miniature pancreas from progenitor cells. The future goal is to use this model to help in the fight against diabetes.
 
The research results has just been published in the scientific journal Development.
Professor Anne Grapin-Botton and her team at the Danish Stem Cell Centre have developed a three-dimensional culture method which enables the efficient expansion of pancreatic cells. The new method allows the cell material from mice to grow vividly in picturesque tree-like structures. The method offers huge long term potential in producing miniature human pancreas from human stem cells. These human miniature organs would be valuable as models to test new drugs fast and effective -- and without the use of animal models.
"The new method allows the cell material to take a three-dimensional shape enabling them to multiply more freely. It's like a plant where you use effective fertilizer, think of the laboratory like a garden and the scientist being the gardener," says Anne Grapin-Botton.
Social cells
The cells do not thrive and develop if they are alone, and a minimum of four pancreatic cells close together is required for subsequent organoid development.
"We found that the cells of the pancreas develop better in a gel in three-dimensions than when they are attached and flattened at the bottom of a culture plate. Under optimal conditions, the initial clusters of a few cells have proliferated into 40,000 cells within a week. After growing a lot, they transform into cells that make either digestive enzymes or hormones like insulin and they self-organize into branched pancreatic organoids that are amazingly similar to the pancreas," adds Anne Grapin-Botton.
The scientists used this system to discover that the cells of the pancreas are sensitive to their physical environment such as the stiffness of the gel and to contact with other cells.
Pancreas and diabetes connection
An effective cellular therapy for diabetes is dependent on the production of sufficient quantities of functional beta-cells. Recent studies have enabled the production of pancreatic precursors but efforts to expand these cells and differentiate them into insulin-producing beta-cells have proved a challenge.
"We think this is an important step towards the production of cells for diabetes therapy, both to produce mini-organs for drug testing and insulin-producing cells as spare parts. We show that the pancreatic cells care not only about how you feed them but need to be grown in the right physical environment. We are now trying to adapt this method to human stem cells," adds Anne Grapin-Botton.

Journal Reference:
  1. C. Greggio, F. De Franceschi, M. Figueiredo-Larsen, S. Gobaa, A. Ranga, H. Semb, M. Lutolf, A. Grapin-Botton. Artificial three-dimensional niches deconstruct pancreas development in vitro. Development, 2013; 140 (21): 4452 DOI: 10.1242/dev.096628
Courtesy: ScienceDaily