Stephan does it again at Nature Communications

This week yet another paper at the nascent e-journal Nature Communications emerges from the publishing machine that is Dr. Stephan Pless.  This was our longest running and most difficult project to date and seeing it come out in such a great journal is fantastic.  I'll let folks read the paper to see what its all about but the summary is that the data (actual and theoretical) support the existence of a repulsive interaction between a co-evolved glutamate and phenylalanine side-chain that serves to 'fine-tune' channel gating by mildly destabilizing the open state of the channel.  There are most likely (many) other (unidentified) players in this crowded region of the channel, including lipids (and their polar head groups), maybe even PIP molecule or two, and the interaction as we describe it requires that the Phe aside chain is more or less fixed and facing the carboxylate of the glutamate side-chain.  But even with all of those qualifiers aside, its a pretty interesting possibility and might be important for the potassium channel's big brother, the sodium channel, where mutations at these sites can lead to inherited arrhythmia and painful syndromes.

This was the first project that Stephan and I decided to tackle in the newly founded lab way back in 2008.  The idea was simple: lets look at the energetic basis for why a group of aromatic phenylalanine and tyrosine residues that cluster around the inner opening of the channel are so important for potassium channel function.  I mean, if you do even modest mutations at any of these sites one ends up with functionally dead or a seriously messed up channel, so these residues must be doing something important, right?  We had just begun setting up the in vivo nonsense suppression in the lab (no small feat itself) and we had a full toolbox of nonnatural derivatives of Phe.......so  it seemed it would an easy way to quickly get a paper out for the lab and for Stephan's postdoc.  How wrong we were.  Almost 100 mutations (thanks, Ana!!), more than a few mix-ups (and emotional ups and downs), and 4+ years later, its out.  Lets just say it was an extended labor to birth this beast, and anesthetic was often required.  We owe a huge debt to our collaborator and friend Harley Kurata and his math wiz undergrad, John-Jose (aka J^2) Nunez for their help with the kinetic schemes and their work on the SCA analysis, which both served to push the story over the top.  Jason played a key chemical role as always with his input and timely turn-around on the synthesis requests.  Working with such great people makes our science better.  period.

See it here.

Congrats all around....and now onto the next one.........

Welcoming Lilia (to the website)

This week, well technically last week, Lilia's webpage went live on the Ahernlab website.  You can now see Lilia's love/hate relationship with the durable yeast strains that she is using in the lab to make some cool new tools.  We are absolutely thrilled to have Lilia on our site and in the lab.

Lilia is what as known as a "dominant positive" player in the lab (opposed to those 'dominant negative' folks).  She is smart, funny and most importantly, she doesn't hesitate to tell me when I'm wrong.  I am a better person and scientist just for knowing her and the lab is a better place because she is here.  We look forward to great things coming from her project and to the good times ahead.  Prost!

Given that its Friday, spring has arrived and the lab has been making some fantastic progress this week  We leave you with this:

http://www.youtube.com/watch?v=MnGzl-OEyGE

Sodium channel review gets top ranking in Biophys J in 2012

Friends of the lab, Filip, Paolo and I, recently put together a review on the regulation of sodium channels by intracellular calcium ions.  Like all channel fields trying to study modulation, things are a bit tricky.  These physiological tweaks of channel gating, wether it be (dreaded) phosphorylation or any other labile modification of channels, Ca2+ regulation of sodium channels has been a function enigma since its initial description.  Simply put, scientists see variable functional effects on channel gating when intracellular calcium levels are varied.  We did our best to summarize these different results and propose a novel mechanism of channel facilitation.  Check out the details here.

Researcher Profile ALERT!! Presenting... STEPHAN PLESS!!

My good friend and colleague Stephan is the latest researcher to be profiled here at the Ahern Lab Blog!! Follow the link to his YouTube video:

http://www.youtube.com/watch?v=fGDJUTCLis0

Next year I will compile all the footage I took from Wreck Beach and we will have an even more intimate portrait of Herr Pless...

Researcher Profile ALERT!! Presenting... ANA NICIFOROVIC!!

The one person who keeps it all together, the glue that prevents us from falling apart, the scientist that can't stop making mutations (because Stephan won't let her), the one and only Ana is featured in the latest instalment of Ahern Researcher profiles. Follow the link to the YouTube video!!:

http://www.youtube.com/watch?v=CwXX05TvrPc

Stephan nabs the cover of Nature Chemical Biology

Stephan makes it 3 in 2011 with a new paper in Nature Chemical Biology to complete his research hat-trick. Thanks to Christina for the awesome cover art, and to the lab for the excellent stuff they do everyday.

Ahern Lab Bonus Video Featurette!!

As promised, here we present an extra dollop of wisdom from Dr. Sam Goodchild on the link between presenting a compelling scientific narative and producing a documentary film. No pipet tips were harmed in the recording of this video.

http://www.youtube.com/watch?v=x3jmqn4bYYA