Neuroligin-3 paper out in Biological Psychiatry!

Just out, our paper on the biology of a synaptic adhesion molecule critically implicated in autism, published in Biological Psychiatry!

This massive paper includes outstanding work from scientists and collaborators at the Max Planck Institute for Multidisciplinary Sciences in Germany, and the University of Turin in Italy. It includes some of the first ever imaging of human synapses (spot the cool cup-shaped presynaptic terminals nestled in the human brainstem ????!), and identifies a molecular mechanism that determines the synaptic localization and transmitter-specificity of Neuroligin-3 between excitatory and inhibitory synapses in the brain. Congrats to everyone involved, a great way to end the year!

Region-Specific Phosphorylation Determines Neuroligin-3 Localization to Excitatory versus Inhibitory Synapses

 

Bek’s paper out in Journal of Cell Biology!

Congrats to Dr. Bek Altas and our collaborator Prof. Hiroshi Kawabe from Gunma University, Japan, who teased apart a complicated network of cellular interactions between neurons and glia in the brain that cause seizures. Mechanisms of proteostasis and downstream ion gradient homeostasis in astrocytes results in epileptiform network activity in neurons, possibly informing about the pathophysiology behind rare forms of epilepsy with gene variants of the ubiquitin pathway. Read all about it!

Nedd4-2-dependent regulation of astrocytic Kir4.1 and Connexin43 controls neuronal network activity

Cas9-RC on the cover of The CRISPR Journal!

Ryan Richardson’s paper describing the development of Cas9-RC, a new CRISPR agent with increased performance for knockin, is out in the October 2023 issue of The CRISPR Journal.

Not only that, but the paper got the cover! Kudos to Cheryl Brandenburg for the beautiful image of knockin neurons and astrocytes using Cas9-RC in the developing mouse brain. Congrats to the whole team for concluding this large piece of Synth Bio meets Dev Neurosci!

We would be delighted to have you try out Cas9-RC for your own knockin needs. Plasmids will become available on Addgene within the next few days!

Cas9-RC Knockin on the cover of The CRISPR Journal

Phosphorylation of Neuroligin-3

Our work on how the synaptic adhesion molecule Neuroligin-3 is targeted to either excitatory or inhibitory synapses based on phosphorylation is now available on the bioRxiv! Congrats to Bekir Altas, Liam Tuffy, Annarita Patrizi and the rest of the team in this international collaboration between the University of Maryland School of Medicine, the Max Planck Institute for Multidisciplinary Sciences, and the University of Turin.

Phosphorylation Determines Whether Neuroligin-3 is at Excitatory or Inhibitory Synapses in Different Regions of the Brain

Never heard of “mTOR outposts”? Now you have!

Read all about our postulate of the curious little things called “mTOR outposts” in this Hypothesis & Theory paper just out in Frontiers in Cellular Neuroscience!

Neuronal mTOR Outposts: Implications for Translation, Signaling, and Plasticity

Happy day for Bek, Andrea, Garrett, and Alex. Appreciations to Helen Bateup and Akira Yoshii for very constructive reviewing; to Gerardo Morfini for editing the Kinase/phosphatase signaling and axonal function in health and disease topic; and to all in the acknowledgements for the fascinating discussions around the concepts in the mTOR outpost model. Be part of those discussions, send us your thoughts!

Congrats to Ryan and co. for “Cas9 fusions for precision in vivo editing” out on the bioRxiv!

The lab’s first pub is a nifty piece of synth bio for genome editing the brain. Richardson et al. describe a platform to test and develop new high-precision genome editing reagents. Some of our new CRISPR fusions, like eRad18-Cas9-CtIP with linear donors, showed up to 45-times higher accuracy at point-mutation editing compared to vanilla CRISPR. Another step toward direct in vivo knockin and in situ gene therapy approaches!

https://www.biorxiv.org/content/10.1101/2020.07.15.199620v1

The Lab goes to Chicago…

(photo by T. Soykan)

The lab has fun recreating Raphael’s “The School of Athens” in Chicago, while presenting at the 2019 meeting of the Society for Neuroscience!

Ryan, Marilyn, and Jeffrey unveiled their new approach to high efficiency in vivo genome engineering with in situ CRISPR:
https://www.abstractsonline.com/pp8/#!/7883/presentation/65807

Bek, Andrea, Noury, and Uriel debuted their findings on how a mutation in a family with intellectual disability affects the dynactin complex and cortical circuit wiring:
https://www.abstractsonline.com/pp8/#!/7883/presentation/66733

Alex presented new findings on how phosphorylation of Neuroligin adhesion molecules determines synapse specificities:
https://www.abstractsonline.com/pp8/#!/7883/presentation/58703

And how reciprocal adhesion gradient matching guides the development of cortical circuitry:
https://www.abstractsonline.com/pp8/#!/7883/presentation/63936

… and Garrett stashed us some sweet top-shelf probes…

Moving Day

Moving day is here! Time for the Poulopoulos Lab to get a new home across the street in Health Sciences Facility III.

Equipment needs bubble wrap, heavy things need lifting, scopes come apart and back together again. And in the midst of this madness, our science doesn’t miss a beat! The heroic investigators of the lab continued cloning and perfusing in between filling crates and hauling off incubators. Everyone working hard… except the guy behind the camera, that is.

 

Goodbye old lab… hello vista from the 9th floor of the new and improved PouLab!!!