BaDoi Phan
badoiphan.bsky.social
BaDoi Phan
@badoiphan.bsky.social
Anesthesia resident, physician scientist
genomics & addiction neurobiology
🌈 &🐱 dad
Ack! The copy paste from twitter failed me. Here’s the most important part of the thread: tinyurl.com/nphpfcenh
Cell Type Specific Enhancers for Dorsolateral Prefrontal Cortex
The dorsolateral prefrontal cortex (DLPFC) is crucial to primate cognitive functions, but a paucity of cell type specific tools limits studies of DLPFC neurocomputational principles. Therefore, we set...
tinyurl.com
December 3, 2024 at 3:54 PM
🌟 15/15 Impact: These tools enable new experiments in primate cognition & potential therapies. Grateful to both labs & collaborators for support! DM for questions! /end
December 2, 2024 at 4:54 PM
🧩 14/15 Biggest achievement: Built pipeline to identify & validate cell-specific tools in primates. Years of work and a huge team effort but worth it! 😮‍💨
December 2, 2024 at 4:54 PM
🔮 13/15 What's next:
- Studying cognitive circuits
- Developing targeted therapies
- Understanding disorders
Just getting started!
December 2, 2024 at 4:54 PM
🎓 12/15 Proud to share resources, contact
@wrstauffer
for details:
- Primate DLPFC cell atlas🧬
- Our ML models💻
- Validated viral toolbox 🧰 🦠
All available to accelerate research! #OpenScience
December 2, 2024 at 4:54 PM
⚠️ 11/15 We're transparent about limitations:
- Some baseline non-specific expression
- Promoter needs optimization
- Viral crosstalk issues in multiplexing
More work ahead!
December 2, 2024 at 4:54 PM
🐭 10/15 Surprising discovery: Our primate enhancers worked in mouse cortex too! Evolution conserved these regulatory elements 🧬 #evolution
December 2, 2024 at 4:54 PM
🔍 9/15 Our validation pipeline:
- Multiplexed screening first
- Single injections to confirm
- Functional testing
Rigorous approach pays off!
December 2, 2024 at 4:54 PM
🧪 8/15 Key finding: Getting specificity right depends on:
- Viral titer (concentration matters!)
- Capsid choice
- Injection parameters
Details matter!
December 2, 2024 at 4:54 PM
⚡️ 7/15 Most exciting part: Used RMacL3-01 to express ChR2. Could control L2/3 neurons with light! First time achieving this specificity in primate DLPFC 🔦 #optogenetics
December 2, 2024 at 4:54 PM
🔋 6/15 Best performers:
- Our RMacL3-01: Targets L2/3 projection neurons (77% specific!)
- RMacL5ET-01: Hits L5 extra long-range projection neurons
Proud of these results! 🎯
December 2, 2024 at 4:54 PM
🎯 5/15 Our viral toolbox: Created AAVs with these enhancers. Like GPS-guided delivery trucks for genes! Tested different viral capsids (PHP.eB, 2YF, X1.1) to optimize delivery 🚛
December 2, 2024 at 4:54 PM
🤖 4/15 The cool part: We developed ML models (SNAIL) to scan thousands of DNA regions & predict enhancers. Turned a needle-in-haystack problem into a targeted search! #MachineLearning
December 2, 2024 at 4:54 PM
🧬 3/15 Our approach: We used snRNA-seq & ATAC-seq from rhesus DLPFC. Found 11 excitatory & 10 inhibitory neuron types conserved in humans🧑🏽‍🦲and rodents🐭! Each with unique molecular fingerprints 🎯 #genomics
December 2, 2024 at 4:54 PM
🔬 2/15 The challenge: How do we study specific neuron types in primate brains? Prior to our work, we lacked tools to target DLPFC neurons, especially in a cell-type specific way #Neuroscience
December 2, 2024 at 4:54 PM