Showing posts with label immunity. Show all posts
Showing posts with label immunity. Show all posts

Monday, 19 August 2013

Geneticists show the COPIA-R7 transposon enhances the immunity of its host against a pathogenic microorganism

Main Category: Genetics
Article Date: 19 Aug 2013 - 1:00 PDT Current ratings for:
Geneticists show the COPIA-R7 transposon enhances the immunity of its host against a pathogenic microorganism
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Transposons are DNA elements that can multiply and change their location within an organism's genome. Discovered in the 1940s, for years they were thought to be unimportant and were called "junk DNA." Also referred to as transposable elements and jumping genes, they are snippets of "selfish DNA" that spread in their host genomes serving no other biological purpose but their own existence.

Now Tokuji Tsuchiya and Thomas Eulgem, geneticists at the University of California, Riverside, challenge that understanding. They report online in the Proceedings of the National Academy of Sciences that they have discovered a transposon that benefits its host organisms.

Working on the model plant Arabidopsis, they found that the COPIA-R7 transposon, which has jumped into the plant disease resistance gene RPP7, enhances the immunity of its host against a pathogenic microorganism that is representative of a large group of fungus-like parasites that cause various detrimental plant diseases.

"We provide a new example for an 'adaptive transposon insertion' event - transposon insertions that can have beneficial effects for their respective host organisms - and uncover the mechanistic basis of its beneficial effects for plants," said Thomas Eulgem, an associate professor of plant cell biology and the senior author of the research paper. "While it has been known for a while that transposon insertions can have positive effects for their respective host organisms and accelerate evolution of their hosts, cases of such adaptive transposon insertions have been rarely documented and are, so far, poorly understood."

The COPIA-R7 transposon affects RPP7 by interfering with the latter's epigenetic code. In contrast to the well known 4-letter genetic DNA code, which provides instructions for the synthesis of proteins, the "epigenetic code" defines the activity states of genes and determines to what extent their genetic information is utilized. Eulgem explained that the transposition of transposons is typically inhibited by epigenetic silencing signals associated with their DNA. Such epigenetic signals are like molecular "flags" or "tags" that are attached to special proteins, around which DNA is wrapped.

A type of molecular flag, referred to as H3K9me2, prohibits transposons from being active and jumping in their host genomes.

"An exciting aspect of our work is that H3K9me2 signals associated with COPIA-R7 have acquired a completely new meaning in RPP7 and promote the activity of this disease-resistance gene," said Eulgem, a member of UC Riverside's Center for Plant Cell Biology. "By modulating levels of this silencing signal in RPP7, plants can adjust the activity of this disease resistance gene.

"Silencing of transposon activity is a complex process that is based on the interplay between different types of epigenetic signals," Eulgem continued. "Typically H3K9me2 is of critical importance for transposon silencing. However, we found H3K9me2 is not important for COPIA-R7 silencing, perhaps because this type of epigenetic signal has acquired a different function within the RPP7 gene. While we found H3K9me2 to promote RPP7 activity, it seems to have lost its function for COPIA-R7 silencing."

Arabidopsis plants use H3K9me2-mediated messenger RNA processing to accurately set RPP7 activity to precisely defined levels. In principle, scientists interested in crop improvement can now use the UCR discovery to design new types of molecular switches based on H3K9me2-mediated messenger RNA processing. Using standard molecular biological methods, transposon sequences that are naturally associated with this epigenetic signal can be inserted into suitable genes and thereby alter the activity levels of these genes.

"Our results are critical for the basic understanding of how transposons can affect the evolution of their hosts - something not well understood at this time," said Tokuji Tsuchiya, the first author of the research paper and an assistant specialist in Eulgem's lab. "Besides this impact on basic research, the epigenetic mechanism we discovered can possibly be utilized for biotechnological crop improvement. In principle, the switch mechanism we discovered can be applied to all crop species that can be genetically modified."

Next, Eulgem plans to expand his lab's research to how plants use the modulation of H3K9me2 levels at COPIA-R7 to dynamically adjust RPP7 activity when they are attacked by a pathogenic microorganism and to explore if this mechanism also applies to additional genes.

"It would make sense to assume that at other transposons, H3K9me2 levels are also modulated during immune responses and that this epigenetic mark affects the activity of other genes that are important for plant immunity," Eulgem said. "If this is true, we have uncovered a completely new genetic - or epigenetic - mechanism that allows plants to sense that they are under pathogen attack and to initiate appropriate immune responses."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our genetics section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

MLA

University of California - Riverside. "Geneticists show the COPIA-R7 transposon enhances the immunity of its host against a pathogenic microorganism." Medical News Today. MediLexicon, Intl., 19 Aug. 2013. Web.
19 Aug. 2013. APA
University of California - Riverside. (2013, August 19). "Geneticists show the COPIA-R7 transposon enhances the immunity of its host against a pathogenic microorganism." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/264954.php.

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'Geneticists show the COPIA-R7 transposon enhances the immunity of its host against a pathogenic microorganism'

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Tuesday, 30 July 2013

MAPS technology may generate vaccines conferring strong immunity at reduced cost and risk

Main Category: Immune System / Vaccines
Article Date: 30 Jul 2013 - 2:00 PDT Current ratings for:
MAPS technology may generate vaccines conferring strong immunity at reduced cost and risk
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A new method of vaccine design, called the Multiple Antigen Presentation System (MAPS), may result in vaccines that bring together the benefits of whole-cell and acellular or defined subunit vaccination. The method, pioneered by researchers at Boston Children's Hospital, permits rapid construction of new vaccines that activate mulitple arms of the immune system simultaneously against one or more pathogens, generating robust immune protection with a lower risk of adverse effects.

As reported by Fan Zhang, PhD, Ying-Jie Lu, PhD, and Richard Malley, MD, from Boston Children's Division of Infectious Disease, in the Proceedings of the National Academy of Sciences on July 29, the method could speed development of new vaccines for a range of globally serious pathogens, or infectious agents.

Broadly speaking, the vaccines available today fall into two categories: whole-cell vaccines, which rely on weakened or killed bacteria or viruses; and acellular or subunit vaccines, which include a limited number of antigens - portions of a pathogen that trigger an immune response. Both approaches have advantages and disadvantages.

"Whole-cell vaccines elicit a broad range of immune responses, often just as an infection would, but can cause side effects and are hard to standardize," said Malley. "Acellular vaccines can provide good early immunity with less risk of side effects, but the immune responses they induce wane with time."

The MAPS method may allow vaccine developers to take a middle ground, where they can link multiple protein and polysaccharide (sugar) antigens from one or more pathogens together in a modular fashion, much as one would connect Lego blocks.

The resulting complex - which resembles a scaffold of polysaccharides studded with proteins - can stimulate both antibody and T-cell responses simultaneously much like whole-cell vaccines, resulting in stronger immunity to the source pathogen(s). However, because the composition of a MAPS vaccine is well defined and based on the use of isolated antigens (as one would find with an acellular vaccine) the risk of side effects should be greatly reduced.

For instance, mice injected with a MAPS vaccine combining proteins from tuberculosis (TB) and polysaccharides from Streptococcus pneumoniae (pneumococcus) mounted vigorous antibody and T-cell responses against TB, whereas those vaccinated with TB protein antigens alone mounted only an antibody response.

Similarly, 90 percent of mice given a MAPS-based vaccine containing multiple pneumococcal polysaccharide and protein antigens were protected from a lethal pneumococcus infection, mounting strong antibody and T-cell responses against the bacteria. By contrast, 30 percent of mice vaccinated with the same antigens in an unbound state survived the same challenge.

"The MAPS technology gives you the advantages of: whole-cell vaccines while being much more deliberate about which antigens you include; doing it in a quantitative and precise way; and including a number of antigens so as to try to replicate the effectiveness of whole-cell vaccination," Malley explained. "The immunogenicity of these constructs is greater than the sum of their parts, somewhat because they are presented to the host as particles."

The system relies on the interactions of two compounds, biotin and rhizavidin, rather than covalent binding as is used in most of the current conjugate vaccines. To build a MAPS vaccine, biotin is bound to the polysaccharide(s) of choice and rhizavidin to the protein(s). The biotin and rhizavidin then bind together through an affinity interaction analogous to Velcro. The construction process is highly efficient, significantly reducing the time and cost of vaccine development and production.

While his team's initial work has focused on bacterial pathogens, Malley believes the technology could impact vaccine development for a broad range of pathogens, in particular those of importance in the developing world. "Technically, one could construct MAPS vaccines for viruses, parasites, even cancer antigens," he said. "And the modularity is such that one could include antigens from multiple pathogens into the same vaccine, allowing the development of combinatorial vaccines much more efficiently."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our immune system / vaccines section for the latest news on this subject.

Fan Zhang, Ying-Jie Lu, and Richard Malley "Multiple antigen-presenting system (MAPS) to induce comprehensive B- and T-cell immunity" Published online before print July 29, 2013, doi: 10.1073/pnas.1307228110

The study was supported by the National Institute for Allergy and Infectious Diseases (grant R01AI067737) and the Translational Research Program at Boston Children's Hospital.

Boston Children's Hospital

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Hospital, Boston Children\'s. "MAPS technology may generate vaccines conferring strong immunity at reduced cost and risk." Medical News Today. MediLexicon, Intl., 30 Jul. 2013. Web.
30 Jul. 2013. APA

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'MAPS technology may generate vaccines conferring strong immunity at reduced cost and risk'

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Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.



View the original article here