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

 

In utero prime editing of epilepsy variant on bioRxiv!

Modeling an ultra-rare epilepsy variant in wildtype mice with in utero prime editing

For all genome editing fans out there, check out our latest study on bioRxiv showcasing in utero prime editing to model an epilepsy patient with an ultra-rare GRIN variant. To our knowledge, this marks a significant milestone as the first prime editing of neurons in vivo!

Led by Colin Robertson in our lab, alongside Patrick Davis from Boston Children’s Hospital and Harvard Medical School, this ambitious project aims to make precision medicine more accessible to a broad patient population. This rapid workflow to generate personalized animal models with prime editing we hope is a step toward enabling individuals with rare genetic epilepsies to test and tailor pharmacotherapy on their personalized models, reducing the burdens of exploring treatments.

A big thank you for the collaborative efforts of the team, including our partner UM-MIND labs of Peter Crino, Phil Iffland, Steffen Wolff, Brian Mathur, and Ivy Dick; as well as our wonderful collaborators from U Pitt, Eldin Jašarević, and UC Anschutz, Tracy Bale! Thank you all for this achievement and the fantastic collaboration we enjoy!

We look forward to this research advancing toward bedside-to-bench applications!

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

PouLab posters at SfN 2023

Calling all Neuroscientists!!!

Come check out all the PouLab posters at SfN 2023

Sunday pm session: “Genetic Techniques to Target and/or Manipulate Cells”, three back-to-back posters :

Monday am session “Animal Models of Epilepsy: Genetics and Pharmacology”:

Wednesday pm session “Mechanisms Underlying Axon Growth and Targeting”:

Celebrate neuroscience with us!!!

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

Corinne Martin Named 2023 Goldwater Scholar!!!

Corinne Martin was awarded a 2023 national Goldwater Scholarship!!! We couldn’t be prouder of her! Corinne spent two years as an NSIP intern in the lab, critically working on Pegassist and researching the links between brain development and brain cancer. Corinne’s ideas spawned new paths of investigation on how common cellular pathways in development get aberrantly reactivated in tumor cells. With a Goldwater scholarship, we are all excited to see the new frontiers Corinne will take on at the forefront of biomedical research! Congratulations Corinne!!!

https://eng.umd.edu/news/story/two-umd-bioengineering-majors-named-2023-goldwater-scholars

 

PouLab at SfN 2022

Follow our science at the 4 PouLab posters at SfN 2022 in San Diego!

Cheryl Brandenburg on Monday morning (Y5):
Light sheet mapping of parvalbumin subtypes of Purkinje cells using in vivo CRISPR strategies

Colin Robertson on Monday afternoon (YY36):
Neural somatic genome editing in the brain for personalized patient models

Garrett Bunce and Ro Whitten on Wednesday morning (B31):
The novel gene Ganon-1 produces a scaffolding RNA for growth signaling in developing axon projections

Andrea Romanowski on Wednesday morning (C45):
Mosaic Cas9 fusions to investigate cortical wiring by IgLON schizophrenia risk-genes in the rodent brain”


See you all at #SFN2022