Editing the Brain @ University of Maryland School of Medicine
Our paper with Gene Blatt in Journal of Comparative Neurology on the evolution of neuroanatomical tracing methods came out today with Cheryl’s beautiful electroporated, cleared, and light sheet imaged hippocampus gracing the cover, alongside Dee Pandya’s India Ink traces. Happy New Year everyone!
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!
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!
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!
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!
Did you know that an estimated 40% of RNA in the brain is not captured by single-cell RNAseq?
Explore the intriguing world of the Brain’s Dark Transcriptome in our latest review, published in Current Opinion in Neurobiology! Check out the other great reviews in this special issue on Developmental Neuroscience edited by Debby Silver and Franck Polleux!
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.
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!
Congratulations to Philip Iffland and the Peter Crino Lab –with help from PouLab grad student Andrea Romanowski among the collaborator team– for the publication of a massive piece of work just out in Brain, spanning the fields of human genetics, cell biology, genome editing, electrophysiology, and brain development to identify the gene (NPRL3) and mechanisms that cause epilepsy in affected patients.
“NPRL3 loss alters neuronal morphology, mTOR localization, cortical lamination, and seizure threshold” Brain, 2022
Our protocol on subtype-specific growth cone sorting by Engmann and Hatch et al. is out on Nature Protocols today from Alex’s old team in the Macklis lab@Harvard!