Gene ‘Arc’ transports mRNA across cells and is required for some forms of plasticity

Also it appears to have evolved from viruses.

Elissa D. Pastuzyn, Cameron E. Day, Rachel B. Kearns, Madeleine Kyrke-Smith, Andrew V. Taibi, John McCormick, Nathan Yoder, David M. Belnap, Simon Erlendsson, Dustin R. Morado, John A.G. Briggs, Cédric Feschotte, Jason D. Shepherd. The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer

James Ashley, Benjamin Cordy, Diandra Luci, Lee G. Fradkin, Vivian Budnik, Travis Thomson. Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons

 

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Vector manipulation meets Web2.0

Neurodudes reader (and optogeneticist) Feng Zhang has designed some vector manipulation tools that are freely available online. He writes

My colleague Robert Wang and I created an online collaborative DNA Vector analysis program called everyVECTOR. We were initially motivated because all of the existing commercial software are really expensive and the free ones are not as nicely designed/intuitive to use. Also, I was always frustrated with collaborators sending me text files of DNA sequences that weren’t annotated and confusing to read.

[…] You can also the public interface (without registration) by visiting here.

We released everyVECTOR last week and so far we have received good responses from people. We have around 200 users now from the past week, mostly from the Stanford and bay area universities.

I hope all of you molecular biologists can give everyVECTOR a try and give Feng some feedback. It certainly seems much more affordable (ie. free) than its well-known competitors. I’m a big fan of web-based tools myself and find them invaluable in doing simple sequence calculations for my own projects (one of my favs is the Sequence Manipulation Suite).

Also, apologies for the decreased posting frequency… I’m trying to graduate these days and there just doesn’t seem to be enough hours for everything. I hope to return to full force soon.

Frontiers in Neuroscience Journal

The journal, Frontiers in Neuroscience, edited by Idan Segev, has made it Volume 3, issue 1.  Launching last year at the Society for Neuroscience conference, its probably the newest Neuroscience-related journal.

I’m a fan of it because it is an open-access journal featuring a “tiered system” and more.  From their website:

The Frontiers Journal Series is not just another journal. It is a new approach to scientific publishing. As service to scientists, it is driven by researchers for researchers but it also serves the interests of the general public. Frontiers disseminates research in a tiered system that begins with original articles submitted to Specialty Journals. It evaluates research truly democratically and objectively based on the reading activity of the scientific communities and the public. And it drives the most outstanding and relevant research up to the next tier journals, the Field Journals.

Continue reading

Photoactivatable transcription: Simplicity vs. overengineering

I finally got around to reading the Nature Methods that has been sitting on my coffee table for a few weeks and I was surprised to see an article on photoactivatable transcription using caged doxycycline with standard Tet On/Off genetics. A postdoc in my lab has been suggesting this type of technology for the last few years and speculating about different ways to possibly implement it. What’s so remarkable about this work is the simplicity of the implementation. In our lab (and others), the common assumption has been that the photoactivatable mechanism should be designed such that a recombinase is directly light-activated. (For example, a membrane tethered Cre recombinase where the tether is broken by light and releases the recombinase to the nucleus after illumination.) But that seems a bit overengineered. Is there a simpler way? Yes!

In this work, Cambridge et al. generated a dox analog, cyanodoxycycline, that is better retained inside cells (reduced membrane permeability) and put it inside a stable photoactivatable (UV) cage. Instead of making the system entirely genetic, they use small molecule uncaging (an established technology) to make problem simpler. In this case, standard Tet genetics can be used (thus leveraging existing model organism Tet lines) and the novel caged Dox can be easily added to food, etc. I think this is a great example of finding the simplest solution to a problem that at first seems very complex.

And the uncaging results are quite impressive. Here are two spatial patterns of gene expression in hippocampal slice culture, a smiley face and a single neuron, achieved by clamping down the field stop before illumination:

Picture 3 Picture 4

Inert designer ligand-receptor for genetically targeted activation

Recently, Alexander et al. published Remote Control of Neuronal Activity in Transgenic Mice Expressing Evolved G Protein-Coupled Receptors [Neuron Neurotechniques], in which they use directed evolution techniques to modify a muscarinic GPCR to selectively bind an orally-deliverable small molecule that is otherwise inert. Apparently, this is the first time a channel has been engineered such that is selective for a biologically inert molecule, providing specificity of action. (They compare their technology with the hyperpolarizing allatostatin receptor which can have off-target effects.) Because the channel is specified genetically and the drug circulates systemically, it is easier to activate large populations of neurons (viz. optogenetic methods which are constrained to neurons in the light delivery volume) without implanted devices (eg. cannulas for AlstR, fiber optics for optogenetics, etc.) Another new technique/neurotechnology… onwards marches the innovation of new circuit-cracking tools!