J. K. Wickiser Lab

Posts Tagged ‘Evolution’

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The essential genome of a bacterium: wants versus needs.

Tuesday, October 11, 2011

Lucy Shaprio and colleagues have identifed the minimal set of genes required for caulobacter to thrive on rich media. This work will help others bioengineer the organism to function in a variety of roles involving the production of small molecule metabolites and the generation of biosensor systems.

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Great book to add to the “to read” pile

Tuesday, October 4, 2011

RNA Worlds

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Conspiracy messages in my DNA – oh noes !!!1111111!!!!!!!!!!!!!11111111

Sunday, October 2, 2011

Here’s a fun little pop sci article dealing with encoding messages in DNA. Unfortunately this article takes away from the real news: that aliens hacked up their genomes, inserted them into bacteria, and sent them forward on meteors eons ago to populate different worlds. I’m sure there’s a PhD thesis in there someplace.

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An RNA aptamer “version” of GFP

Friday, September 16, 2011

Cool story bro: Someone wanted to track specific transcripts in vivo so they evolved an aptamer to bind a crippled fluorophore and in doing so, activate it. Yeah. Category: Things I wish I had invented.

Here’s the paper.

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Meeting: The fight against drug resistance in bacteria

Monday, August 29, 2011

Here’s a cool looking meeting at NYAS in a couple months dealing with the evolution of drug resistant strains of microbes.

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Challenges of developing universal vaccines

Wednesday, August 24, 2011

I’ll go to my grave wishing I knew more about immunology. I tend to get lost in the acronyms but here’s a very readable review where the author discusses the challenges in developing universal vaccines.

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Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins.

Wednesday, August 24, 2011

Here are two reviews of a cool paper detailing synthetic RNA switches in the cell.

“I found this paper interesting because the authors describe an innovative step towards engineering a regulatory system that can change the expression of targeted genes.

More importantly, their system senses specific endogenous signals defined by users and responds by directing the cells to an alternative behavior. Indeed, they showed that endogenous signalling pathways can be rerouted to induce novel cellular phenotypes, including apoptosis. Their sensing device is an RNA aptamer that, upon binding to a specific protein, changes its structure and function to modulate the alternative spicing of the gene in which it has been inserted. Their work emphasizes the efficacy and versatility of RNA aptamers for engineering gene regulation systems and hence for gene therapy.
Competing interests: None declared”

Cite this evaluation
DesGroseillers L: “I found this paper interesting because the authors describe an innovative step towards engineering a…” Evaluation of: [Culler SJ et al. Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins. Science. 2010 Nov 26; 330(6008):1251-5; doi: 10.1126/science.1192128]. Faculty of 1000, 03 Feb 2011. F1000.com/7626956

“Molecular biologists usually alter cellular functions by overexpressing, mutating, or knocking down components of transcription factor and signal transduction networks. However, a method for reprogramming cellular behavior in response to any user-defined component of endogenous signaling networks would provide an important tool both for measuring the activities of these networks and using them to tailor cellular function. Culler et al. have managed to devise such a method by engineering what they call, “RNA-based sensing actuation devices”.

Basically, these devices comprise a three-exon mini-gene with two introns. The middle exon includes a translational stop codon that prevents translation of the open reading frame (ORF) encoded in the 3’-most exon. The critical component in this system is an RNA aptamer incorporated into the intronic sequences flanking the middle exon. The aptamer is first generated by in vitro selection to bind to a specific protein ligand. The authors show that association of the specific ligand with the inserted aptamer can act to alternatively splice the mini-gene such that the middle exon containing the stop codon is either included or excluded. The mechanism through which aptamer-ligand interaction influences splicing is unclear and the exact position of the aptamer within the intronic sequences required to trigger alternative splicing must be determined empirically for each aptamer. In principle, these devices could be employed to sense any endogenous protein and to respond by expressing any protein encoded in the 3’ exon ORF.

The authors provide several compelling demonstrations that their sensing devices work quite well. For example, inclusion of an aptamer that binds phage MS2 coat protein results in expression of the green florescent protein (GFP) signal encoded in the 3’ exon ORF in response to expression of the coat protein. Moreover, treatment of cells with exogenous factors that stimulate endogenous nuclear factor kappa B (NFkB)- or Wnt-signaling pathways also produce a robust GFP signal from mini-genes with aptamers binding NFkB p65 or beta-catenin, respectively. They also show that insertion of two aptamers can increase the response and that, at least in some cases, multiple ligands act to evoke a synergistic response. Lastly, they demonstrate that the system can be employed to regulate cell fate decisions. Thus, a mini-gene designed to ‘sense’ beta-catenin and produce the herpes simplex virus thymidine kinase from the 3’ ORF will trigger cell death in the presence of Wnt ligand and the pro-drug Ganciclovir.

This work underscores the versatility of RNA as both a biological sensor and regulator and suggests that the engineering of synthetic networks is within reach (also see related perspective by Liu and Arkin {1}).

References:
{1} Liu and Arkin, Science 2010, 330:1185-6 [PMID:21109657].
Competing interests: None declared”

Cite this evaluation
Eisenman R: “Molecular biologists usually alter cellular functions by overexpressing, mutating, or knocking down components of transcription…” Evaluation of: [Culler SJ et al. Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins. Science. 2010 Nov 26; 330(6008):1251-5; doi: 10.1126/science.1192128]. Faculty of 1000, 19 Jan 2011. F1000.com/7626956

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Synthetic human cell fate regulation by protein-driven RNA switches.

Tuesday, August 23, 2011

Here’s a review of some work relevant to the lab – it describes synthetic RNA switches targeting molecules in humans.

“This study is interesting because the authors demonstrated that human cell fate, death or survival can be controlled by ON/OFF translational switches.

This study specifically dealt with apoptosis. Their RNA switch composed of L7Ae and L7Ae-tagged protein of interest was shown to regulate apoptosis. The ON system represses degradation of a target mRNA by RNA interference and the OFF system is associated with balance modulation of pro-apoptotic and anti-apoptotic proteins. They further explored the effects of the combined use of these ON/OFF switches.

Depending on the gene, any function can be a candidate for study. The result of the present study theoretically means that the cell fate of cancer or specific organs can be controlled. Before that day comes, this technique will be applied to drug delivery systems and will develop in the field of tissue engineering as well. In this respect, this pioneering study is uniquely promising.

References:
{1} Bashor et al. Annu Rev Biophys 2010, 39:515-37 [PMID:20192780].
{2} An et al. RNA 2006, 12:710-6 [PMID:16606868].
Competing interests: None declared”

Cite this evaluation
Nakamoto H, Kajiya F: “This study is interesting because the authors demonstrated that human cell fate, death or survival…” Evaluation of: [Saito H et al. Synthetic human cell fate regulation by protein-driven RNA switches. Nat Commun. 2011 Jan 18; 2:160; doi: 10.1038/ncomms1157]. Faculty of 1000, 23 Feb 2011. F1000.com/8579956

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NASA, the undisputed King of Press Releases

Thursday, August 11, 2011

A team from NASA is claiming to have found nucleobase-like molecules on a meteorite. They also claim that their signal (unusual nucleobase analogs to include 2,6-diaminopurine) is well above background and is not found in terrestrial controls. As much as I want to implicitly trust this data, my experience with NASA biochemistry is that they shoot first and think/ask questions later. But the one thing they do better than anyone else: crow about it.

Check these out:

PR: http://lightyears.blogs.cnn.com/2011/08/11/dna-discovered-in-meteorites/

http://www.outlookseries.com/A0996/Science/3824_Michael_Callahan_NASA_Nucleobases_DNA_Building_Blocks_Can_Made_Space_Michael_Callahan.htm

PNAS paper

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The network of coral, good bacteria, and bad bacteria

Sunday, April 4, 2010

Great paper in PLoS mapping a network between the good and bad actors:

http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1000345

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