Using genes as interchangeable parts, synthetic biologists design cellular circuits that can perform new functions, such as sensing environmental conditions. However, the complexity that can be achieved in such circuits has been limited by a critical bottleneck: the difficulty in assembling genetic components that don't interfere with each other.
Unlike electronic circuits on a silicon chip, biological circuits inside a cell cannot be physically isolated from one another. "The cell is sort of a burrito. It has everything mixed together," says Christopher Voigt, an associate professor of biological engineering at MIT.
Because all the cellular machinery for reading genes and synthesizing proteins is jumbled together, researchers have to be careful that proteins that control one part of their synthetic circuit don't hinder other parts of the circuit.
Voigt and his students have now developed circuit components that don't interfere with one another, allowing them to produce the most complex synthetic circuit ever built. The circuit, described in the October 11 issue of Nature, integrates four sensors for different molecules. Such circuits could be used in cells to precisely monitor their environments and respond appropriately.
"It's incredibly complex, stitching together all these pieces," says Voigt, who is co-director of the Synthetic Biology Center at MIT. Larger circuits would require computer programs that Voigt and his students are now developing, which should allow them to combine hundreds of circuits in new and useful ways.
Lead author of the paper is MIT postdoc Tae Seok Moon. Other authors are MIT postdoc Chunbo Lou and Alvin Tamsir, a graduate student at the University of California at San Francisco.
Expanding the possibilities
Previously, Voigt has designed bacteria that can respond to light and capture photographic images, and others that can detect low oxygen levels and high cell density ? both conditions often found in tumors. However, no matter the end result, most of his projects, and those of other synthetic biologists, use a small handful of known genetic parts. "We were just repackaging the same circuits over and over again," Voigt says.
To expand the number of possible circuits, the researchers needed components that would not interfere with each other. They started out by studying the bacterium that causes salmonella, which has a cellular pathway that controls the injection of proteins into human cells. "It's a very tightly regulated circuit, which is what makes it a good synthetic circuit," Voigt says.
The pathway consists of three components: an activator, a promoter and a chaperone. A promoter is a region of DNA where proteins bind to initiate transcription of a gene. An activator is one such protein. Some activators also require a chaperone protein before they can bind to DNA to initiate transcription.
The researchers found 60 different versions of this pathway in other species of bacteria, and found that most of the proteins involved in each were different enough that they did not interfere with one another. However, there was a small amount of crosstalk between a few of the circuit components, so the researchers used an approach called directed evolution to reduce it. Directed evolution is a trial-and-error process that involves mutating a gene to create thousands of similar variants, then testing them for the desired trait. The best candidates are mutated and screened again, until the optimal gene is created.
Layered circuits
To design synthetic circuits so they can be layered together, their inputs and outputs must mesh. With an electrical circuit, the inputs and outputs are always electricity. With these biological circuits, the inputs and outputs are proteins that control the next circuit (either activators or chaperones).
These components could be useful for creating circuits that can sense a variety of environmental conditions. "If a cell needs to find the right microenvironment ? glucose, pH, temperature and osmolarity [solute concentration] ? individually they're not very specific, but getting all four of those things really narrows it down," Voigt says.
The researchers are now applying this work to create a sensor that will allow yeast in an industrial fermenter to monitor their own environment and adjust their output accordingly.
###
Massachusetts Institute of Technology: http://web.mit.edu/newsoffice
Thanks to Massachusetts Institute of Technology for this article.
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
ScienceDaily (Oct. 10, 2012) ? Single fatherhood is a challenge many arachnids undertake, guarding eggs laid by females despite the costs to their own health and mating benefits, but the news may not be all bad for these dads.
New research now shows that, in one species of spiders, males exclusively responsible for guarding eggs actually enjoy survival benefits rather than suffer losses to health or mating privileges. The study, published Oct. 10 in the open access journal PLOS ONE by Gustavo Santos Requena and colleagues from the University of Sao Paulo, Brazil, evaluates the costs and benefits of exclusive paternal care, the rarest form of parental investment in nature, in the harvestman spider Iporangaia pustulosa.
The researchers tracked spiders in the forests of southeastern Brazil over the course of a year to observe how caring behavior in males affected their chances of survival or body condition. Though caring males feed very rarely and lose body condition while guarding eggs, the authors found that these spiders suffered no long-term decrease in fitness compared to females or non-caring males. Their sedentary behavior during the caring period also makes them less likely to be eaten by predators, reducing their mortality risk. The authors also suggest that providing females cost-free care for their offspring might make caring males more attractive to females, thereby improving their chances for reproductive success.
According to the authors, their results suggest that the reduction in mortality risk, combined with the genetic advantages of improving survival of their offspring, may have played important roles in favoring the evolution of paternal care in insects.
Share this story on Facebook, Twitter, and Google:
Other social bookmarking and sharing tools:
Story Source:
The above story is reprinted from materials provided by Public Library of Science.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
Requena GS, Buzatto BA, Martins EG, Machado G. Paternal Care Decreases Foraging Activity and Body Condition, but Does Not Impose Survival Costs to Caring Males in a Neotropical Arachnid. PLoS ONE, 2012; 7(10): e46701 DOI: 10.1371/journal.pone.0046701
Note: If no author is given, the source is cited instead.
Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.
No Investment Needed! Convert Your Spare Time Into Cash. Make Money Online Using One Of The Best Kept Internet Secrets. Learn How Fortune 500 Companies Are Willing To Pay You Top Dollar For Your Help While Working Online At Home At Your Own Convenience.
WIP, [ 1 x 1 with WittyWriter88 and I, you may not join, though feel free to browse, and ask for private RPs if you like what you see here (: ]
Owner:
Game Masters:
This topic is an Out Of Character part of the roleplay, ?Darkest Eternity?. Anything posted here will also show up there.
Topic Tags:
Forum for completely Out of Character (OOC) discussion, based around whatever is happening In Character (IC). Discuss plans, storylines, and events; Recruit for your roleplaying game, or find a GM for your playergroup.
Post a reply
RolePlayGateway is a site built by a couple roleplayers who wanted to give a little something back to the roleplay community. The site has no intention of earning any profit, and is paid for out of their own pockets.
If you appreciate what they do, feel free to donate your spare change to help feed them on the weekends. After selecting the amount you want to donate from the menu, you can continue by clicking on PayPal logo.
BERLIN (Reuters) - A German insurance giant revealed employees put a trip to a swingers' hotel in Jamaica on company expenses when it published the results of an internal audit on a public website.
The reputation of Ergo, the primary insurance unit of Munich Re, the world's biggest reinsurer, suffered a blow last year when a German newspaper reported that a subsidiary had hosted a sex party in Budapest in 2007 to reward top employees.
On Sunday, Ergo unveiled a website containing details of 12 similar incidents. It showed employees had also charged the company for tickets to a strip club in Estonia.
In a statement, Ergo head Torsten Oletzky said the company had decided to publish the results of an internal audit of more than 500 incentive trips in the interests of transparency.
"With the published material, you can make your own judgment," Oletzky said.
(Reporting by Chris Cottrell; editing by Robert Woodward)
Study Linking Monsanto Corn to Cancer Must Be Taken Seriously by Regulators
last week, Seralini brought the whole scientific and corporate establishment crashing down on his head. In a peer-reviewed US journal, Food and Chemical Toxicology, he ...
Today | News Report (Article)
Close this panel
Thanks for your review!
Your review has been saved, but will not be published due to your member status. For help, check our .
Phase III data in treatment of renal cell carcinoma reportedPublic release date: 1-Oct-2012 [ | E-mail | Share ]
Contact: ESMO PRESS OFFICE media@esmo.org European Society for Medical Oncology
New trial results on pazopanib and temsirolimus have important implications for patients
Vienna, Austria, 1 October 2012 New results from phase III trials exploring treatment options for patients with advanced renal cell carcinoma were released at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.
Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes (tubules) in the kidney.
Prof Maria De Santis from Kaiser Franz Josef-Spital, Vienna, Chair of the ESMO 2012 Genitourinary program track (who was not involved in the studies) commented: "At this year's ESMO congress, three urgently awaited and highly ranked randomized phase III trials in the area of renal cell carcinoma are being presented. All three studies are important, although two of these studies are so called 'negative' studies (INTORACT and INTORSECT)."
"These studies are significant because they increase our knowledge about the use of targeted treatment options, in particular temsirolimus, sorafenib, bevacizumab and pazopanib," Prof De Santis said. "Most importantly, one of the studies, the COMPARZ trial, allows us to define a standard option in the front line treatment of renal cell carcinoma, because it was proven that pazopanib is non-inferior to sunitinib. In addition, being treated with pazopanib, patients experienced fewer troublesome side-effects and an increased quality of life."
COMPARZ trial: pazopanib and sunitinib similarly effective in first line treatment of metastatic renal cell carcinoma
The new drug pazopanib has similar efficacy to sunitinib in controlling metastatic renal cell carcinoma, the results of the phase III randomized, open-label COMPARZ trial show.
Sunitinib and pazopanib are both targeted drugs available for first line treatment of metastatic renal cell carcinoma. Sunitinib has been considered as the reference standard, although non-randomized trials have suggested similar efficacy with pazopanib, and less incidence of some side effects found troublesome to patients.
Dr Robert Motzer from Memorial Sloan Kettering Cancer Center, New York, USA and colleagues set out to compare the efficacy, safety, and quality of life for pazopanib and sunitinib in a global, 1100-patient phase III trial. The primary endpoint was to establish non-inferiority of progression-free survival, and safety and quality of life were evaluated as secondary endpoints, as well.
"The trial showed that pazopanib had similar efficacy (i.e non-inferiority) compared to sunitinib in first-line treatment of metastatic renal cell carcinoma," Dr Motzer said. "The main endpoint for assessment was progression-free survival, and we looked at other endpoints as well, including response, overall survival, safety and quality of life."
For both drugs, the median progression-free survival by the treating physician's assessment was slightly more than 10 months.
Both drugs resulted in side effects, but some of those recognized to be troublesome to patients, such as fatigue and skin sores, occurred with less frequency for pazopanib than with sunitinib, the researchers found.
"The quality-of-life questionnaires were in favor of pazopanib over sunitinib, and suggested improved tolerability for pazopanib over sunitinib," Dr Motzer said.
INTORSECT trial: Temsirolimus does not demonstrate superiority in survival over sorafenib in second-line treatment
The results of a phase III trial comparing two commonly used drugs in the second-line treatment of renal cell carcinoma suggest that temsirolimus does not improve survival over sorafenib in the second line setting.
The two drugs inhibit different cancer-associated molecules: temsirolimus targets mTOR, which regulates cell growth and proliferation, while sorafenib inhibits several tyrosine kinases, including VEGF receptors.
"This is the first head-to-head phase III trial comparing a VEGF inhibitor to an mTOR inhibitor in renal cell carcinoma, reporting final results. Hence, this trial will have important treatment implications for patients and physicians," said Dr Thomas Hutson from Texas Oncology-Baylor Charles A Sammons Cancer Center in Texas, USA.
Temsirolimus had demonstrated an overall survival benefit compared to interferon alfa in previously untreated patients with advanced renal cell carcinoma and poor prognostic features, but the drug's efficacy after treatment with a VEGF inhibitor was not known, Dr Hutson explained.
The INTORSECT Trial included 511 renal cell carcinoma patients from 112 sites, whose disease progressed after first-line sunitinib therapy and who had an ECOG performance status of 0 or 1. Median progression-free survival with temsirolimus was 4.28 months compared to 3.91 months with sorafenib. Median overall survival for the temsirolimus group was 12.27 months compared to 16.64 months for those who received sorafenib.
Based on these results, the researchers found that temsirolimus did not show superiority to sorafenib in the primary end point of progression-free survival or in the secondary end point of overall survival.
"This trial shows drugs that inhibit the VEGF pathway may be a better option than mTOR inhibitors for patients progressing on sunitinib," Dr Hutson said. "In addition, mTOR inhibitors may be appropriate for first line use for a select group of non-clear cell renal cell carcinoma patients and/or those patients with poor performance status."
INTORACT Trial: bevacizumab plus temsirolimus offers no advantage over bevacizumab plus interferon
A phase III trial has failed to confirm early clinical results with the combination of bevacizumab and temsirolimus in renal cell carcinoma, investigators from the INTORACT trial report.
The two drugs target separate molecular pathways involved in renal cell carcinoma, and early results had seemed promising, said Prof Brian Rini, a staff physician at the Cleveland Clinic's Taussig Cancer Institute in Cleveland, Ohio and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Cleveland, Ohio.
The INTORACT trial, a global phase IIIb, randomized, open-label, multi-center study, compared temsirolimus plus bevacizumab with interferon plus bevacizumab as first-line treatment in 791 patients with predominantly clear cell metastatic renal cell carcinoma.
At the data cutoff for final analysis, 489 patients had independently assessed progression-free survival events. Median progression-free survival with the temsirolimus combination was 9.1 months, compared to 9.3 months in the interferon group. Median overall survival was 25.8 months in the temsirolimus group and 25.5 months for the interferon group.
This study failed to find an advantage to the combination of bevacizumab and temsirolimus over bevacizumab and interferon, therefore did not confirm preliminary results of this combination," Prof Rini said.
###
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Phase III data in treatment of renal cell carcinoma reportedPublic release date: 1-Oct-2012 [ | E-mail | Share ]
Contact: ESMO PRESS OFFICE media@esmo.org European Society for Medical Oncology
New trial results on pazopanib and temsirolimus have important implications for patients
Vienna, Austria, 1 October 2012 New results from phase III trials exploring treatment options for patients with advanced renal cell carcinoma were released at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.
Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes (tubules) in the kidney.
Prof Maria De Santis from Kaiser Franz Josef-Spital, Vienna, Chair of the ESMO 2012 Genitourinary program track (who was not involved in the studies) commented: "At this year's ESMO congress, three urgently awaited and highly ranked randomized phase III trials in the area of renal cell carcinoma are being presented. All three studies are important, although two of these studies are so called 'negative' studies (INTORACT and INTORSECT)."
"These studies are significant because they increase our knowledge about the use of targeted treatment options, in particular temsirolimus, sorafenib, bevacizumab and pazopanib," Prof De Santis said. "Most importantly, one of the studies, the COMPARZ trial, allows us to define a standard option in the front line treatment of renal cell carcinoma, because it was proven that pazopanib is non-inferior to sunitinib. In addition, being treated with pazopanib, patients experienced fewer troublesome side-effects and an increased quality of life."
COMPARZ trial: pazopanib and sunitinib similarly effective in first line treatment of metastatic renal cell carcinoma
The new drug pazopanib has similar efficacy to sunitinib in controlling metastatic renal cell carcinoma, the results of the phase III randomized, open-label COMPARZ trial show.
Sunitinib and pazopanib are both targeted drugs available for first line treatment of metastatic renal cell carcinoma. Sunitinib has been considered as the reference standard, although non-randomized trials have suggested similar efficacy with pazopanib, and less incidence of some side effects found troublesome to patients.
Dr Robert Motzer from Memorial Sloan Kettering Cancer Center, New York, USA and colleagues set out to compare the efficacy, safety, and quality of life for pazopanib and sunitinib in a global, 1100-patient phase III trial. The primary endpoint was to establish non-inferiority of progression-free survival, and safety and quality of life were evaluated as secondary endpoints, as well.
"The trial showed that pazopanib had similar efficacy (i.e non-inferiority) compared to sunitinib in first-line treatment of metastatic renal cell carcinoma," Dr Motzer said. "The main endpoint for assessment was progression-free survival, and we looked at other endpoints as well, including response, overall survival, safety and quality of life."
For both drugs, the median progression-free survival by the treating physician's assessment was slightly more than 10 months.
Both drugs resulted in side effects, but some of those recognized to be troublesome to patients, such as fatigue and skin sores, occurred with less frequency for pazopanib than with sunitinib, the researchers found.
"The quality-of-life questionnaires were in favor of pazopanib over sunitinib, and suggested improved tolerability for pazopanib over sunitinib," Dr Motzer said.
INTORSECT trial: Temsirolimus does not demonstrate superiority in survival over sorafenib in second-line treatment
The results of a phase III trial comparing two commonly used drugs in the second-line treatment of renal cell carcinoma suggest that temsirolimus does not improve survival over sorafenib in the second line setting.
The two drugs inhibit different cancer-associated molecules: temsirolimus targets mTOR, which regulates cell growth and proliferation, while sorafenib inhibits several tyrosine kinases, including VEGF receptors.
"This is the first head-to-head phase III trial comparing a VEGF inhibitor to an mTOR inhibitor in renal cell carcinoma, reporting final results. Hence, this trial will have important treatment implications for patients and physicians," said Dr Thomas Hutson from Texas Oncology-Baylor Charles A Sammons Cancer Center in Texas, USA.
Temsirolimus had demonstrated an overall survival benefit compared to interferon alfa in previously untreated patients with advanced renal cell carcinoma and poor prognostic features, but the drug's efficacy after treatment with a VEGF inhibitor was not known, Dr Hutson explained.
The INTORSECT Trial included 511 renal cell carcinoma patients from 112 sites, whose disease progressed after first-line sunitinib therapy and who had an ECOG performance status of 0 or 1. Median progression-free survival with temsirolimus was 4.28 months compared to 3.91 months with sorafenib. Median overall survival for the temsirolimus group was 12.27 months compared to 16.64 months for those who received sorafenib.
Based on these results, the researchers found that temsirolimus did not show superiority to sorafenib in the primary end point of progression-free survival or in the secondary end point of overall survival.
"This trial shows drugs that inhibit the VEGF pathway may be a better option than mTOR inhibitors for patients progressing on sunitinib," Dr Hutson said. "In addition, mTOR inhibitors may be appropriate for first line use for a select group of non-clear cell renal cell carcinoma patients and/or those patients with poor performance status."
INTORACT Trial: bevacizumab plus temsirolimus offers no advantage over bevacizumab plus interferon
A phase III trial has failed to confirm early clinical results with the combination of bevacizumab and temsirolimus in renal cell carcinoma, investigators from the INTORACT trial report.
The two drugs target separate molecular pathways involved in renal cell carcinoma, and early results had seemed promising, said Prof Brian Rini, a staff physician at the Cleveland Clinic's Taussig Cancer Institute in Cleveland, Ohio and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Cleveland, Ohio.
The INTORACT trial, a global phase IIIb, randomized, open-label, multi-center study, compared temsirolimus plus bevacizumab with interferon plus bevacizumab as first-line treatment in 791 patients with predominantly clear cell metastatic renal cell carcinoma.
At the data cutoff for final analysis, 489 patients had independently assessed progression-free survival events. Median progression-free survival with the temsirolimus combination was 9.1 months, compared to 9.3 months in the interferon group. Median overall survival was 25.8 months in the temsirolimus group and 25.5 months for the interferon group.
This study failed to find an advantage to the combination of bevacizumab and temsirolimus over bevacizumab and interferon, therefore did not confirm preliminary results of this combination," Prof Rini said.
###
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
No Investment Needed! Convert Your Spare Time Into Cash. Make Money Online Using One Of The Best Kept Internet Secrets. Learn How Fortune 500 Companies Are Willing To Pay You Top Dollar For Your Help While Working Online At Home At Your Own Convenience.
![[ Back to EurekAlert! ]](https://lh3.googleusercontent.com/blogger_img_proxy/AEn0k_tin7OzBSlJYJ0hf4Bdhe-ubSL27P5qTMfOImNMm8mh0K-RcdolI_3xrjCsN9kp1EQ30PpISsh30iRYQW_gJTi7Rov6CmAt2gsdYtSNkPo=s0-d){kind=small}
Public release date: 1-Oct-2012
Share ]