Opening for Research Technologist I

We currently have an opening for a full time tech position: https://psu.jobs/job/85310

This is a great position for somebody looking to get some concentrated time in the lab to develop their research skills. It could be a good fit for an early career tech or a great transitional job for a graduating student looking to strengthen their research experience before moving on to professional school. If you don’t fit those categories but think the job might be a fit for you, apply – you might be right!

New lab publications

We had a couple of nice publications late last year that are worth a mention:

The S6 gate in regulatory Kv6 subunits restricts heteromeric K+ channel stoichiometry http://jgp.rupress.org/content/150/12/1702

This paper was the core of Aditya’s thesis and is a great example of how you can use evolution to highlight key features of proteins. K+ channels are tetrameric and can typically form as homotetramers composed of four identical subunits. However, some subunits have evolved a “regulatory” phenotype in which they can no longer make homotetramers and instead depend on mixing with other closely-related K+ channel subunits to form functional channels, often in an unusual asymmetric 3:1 ratio. We identified sequence changes that correlated with evolution of the regulatory phenotype and found that the interface between subunits in the lining of the pore itself played a key role in determining channel composition. Previously, it had been thought that a cytoplasmic sorting domain, T1, was fully responsible for channel subunit composition. We proposed a two-step model of how you can evolve asymmetric channels that involves sequential mutation of T1 and the pore. This is one of those typical JGP papers with heroically complicated biophysics experiments. We also received a great assist from the Hancock lab who worked with us to count subunits in individual channels using fluorescent tags.

Evolution and Structural Characteristics of Plant Voltage-Gated K+ Channels http://www.plantcell.org/content/early/2018/11/01/tpc.18.00523

This a review Greg and I wrote with Sally on the evolution of Plant Voltage-Gated K+ channels and the CNBD channel superfamily to which they belong. We managed to squeeze a lot of new analyses into it, so its sort of a hybrid review/research article. Here is my favorite thing in the article: 1) CNBD superfamily channels, which include the plant channels and a wide range of animal channels that control sensory perception, neuronal excitability and heartbeat, come from a prokaryotic ancestor that is common in eubacterial lineages but appears to be absent (at least so far) in the Archaea. Since eukaryotes evolved from the Archaeal lineage, that could mean we picked up the CNBD channel superfamily by lateral gene transfer. There of course are plenty of documented cases of lateral gene transfer, but I still think its amazing that the channels that we use to see and smell and the channels that plants depend on to open and close their leaf pores may have been “borrowed” from bacteria. The Plant Cell is of course nothing new to Sally, but it was nice for me to bag another top journal for my “life list”.

Research Opportunities

Its hard to believe the semester officially starts next week! Welcome to new students and welcome back to those who are returning! Our lab is looking for new members at both the undergraduate and graduate levels. We have a wide variety of projects examining the function and evolution of neurons and neuronal signaling, and we are looking for highly motivated students to expand our team. If you are looking for research experience in cellular and molecular neurobiology and are interested in a career in the biological or biomedical sciences, consider joining us. All inquiries should be directed to Tim Jegla (tjj3@psu.edu)

Rewriting the evolutionary history of the neuron

Almost all features of our neurons, from the ion channels that underlie electrical signaling to cellular structures such as axons, dendrites and synapses are ancient and are therefore shared among all living bilaterian animals. However, one critical feature that appeared to have a much more recent evolutionary origin was the axon initial segment (AIS), a specialized compartment at the beginning of the axon that serves as a barrier for maintaining axon identity and as the site of action potential initiation. The AIS was believed to be a recent vertebrate innovation for precision signaling, because the giant ankyrins which link AIS ion channels to the cytoskeleton and are required for barrier formation were believed to be vertebrate-specific. We collaborated with the Rolls lab to show that giant ankyrins instead have a much earlier origin in an ancestor of all bilaterians. They appear to organize an AIS-like domain in the axons of fly sensory neurons, suggesting that the AIS itself is part of that ancient, shared bilaterian neuronal heritage. We think this work will establish Drosophila as a model system for detailed molecular genetic dissection of AIS function. This is important because AIS biology has many important open questions and AIS dysfunction plays a role in a variety of nervous system disorders.

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006457

Nicotinamide (vitamin B3) activates invertebrate TRPV sensory channels

Check out the link below for Wendy Hanna-Rose’s story on identifying nicotinamide as the first endogenous activator of sensory TRPV channels in invertebrates. The most notable role for our TRPV channels are as heat sensors, and compounds such as capsaicin in chili peppers can activate them. Invertebrates seem to use TRPV channels mainly for mechanosensation – they have been studied for years in C. elegans, but nobody had ever been able to functionally express them until Wendy’s lab did a series of elegant genetic studies that suggested nicotinamide could be an agonist for worm TRPVs. Her grad student Avni Upadhyay found that in worm mutants with elevated nicotinamide levels, cells expressing two TRPV channel subunits OSM-9 and OCR-4 die. This phenotype could be rescued by knocking out either TRPV subunit. We confirmed that nicotinamide directly activates both worm and fly TRPVs. We also worked with Will Hancock’s lab (and Keith Mickoajczyk in particular) to figure out that nicotinamide-sensitive worm TRPVs form functional channels as a 2:2 heteromer of OSM-9 and OCR-4 subunits.

http://news.psu.edu/story/431502/2016/10/12/research/too-much-form-vitamin-b3-cells-can-cause-behavioral-changes-worms

Complex nerve-cell signaling traced back to common ancestor of humans and sea anemones

Check out the Eberly College news story on our PNAS paper exploring the evolutionary origins of voltage-gated K+ channels. We find that many of the key channel types that shape electrical signals in our neurons were actually missing in the first nervous systems. However, they are still ancient and we can trace them all back to a common ancestor of humans and cnidarians (animals like sea anemones and jellyfish). We want to know why – what important event was going on in nervous system evolution at that time?

http://science.psu.edu/news-and-events/2015-news/Jegla2-2015

Early evolution of a cardiac ion channel

Check out this Huck Institute story on our 2014 PNAS paper exploring the functional evolution of Erg K+ channels, which play a key role in repolarizing cardiac action potentials. We show the specialized way these channels work evolved before we split from animals like sea anemones hundreds of millions of years before they picked up a role in the heart.

https://www.huck.psu.edu/content/about/news-archive/human-heart-beats-using-nearly-billion-year-old-molecular-mechanism