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