Very excited to share the first paper from my lab. We engineered a new PTEN sensor that permits dynamic imaging in living cells. We showed that this allows to visualize PTEN activity with subcellular resolution in the intact brain. Now published in Nature Methods

RT @HornsteinLab: Excited to share our preprint: "𝐎𝐫𝐠𝐚𝐧𝐞𝐥𝐥𝐨𝐦𝐢𝐜𝐬: 𝐀𝐈-𝐝𝐫𝐢𝐯𝐞𝐧 𝐝𝐞𝐞𝐩 𝐨𝐫𝐠𝐚𝐧𝐞𝐥𝐥𝐚𝐫 𝐩𝐡𝐞𝐧𝐨𝐭𝐲𝐩𝐢𝐧𝐠 𝐫𝐞𝐯𝐞𝐚𝐥𝐬 𝐧𝐨𝐯𝐞𝐥 𝐀𝐋𝐒 𝐦𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐦𝐬 𝐢𝐧 𝐡𝐮𝐦𝐚….

RT @naturemethods: Out today from the Laviv lab! A first-in-class fluorescence lifetime-based FRET sensor for PTEN enables the dynamic moni….

You can find more details in my previous preprint tweet .Paper is available here: Plasmids will be available in @Addgene soon.

This project was spearheaded by Tomar Kagan, a talented PhD student in my lab, with help from other lab members, and collaborators who were invaluable to complete this project. @EickholtL @Sharbeleid97 @of_sagol.

RT @ScienceMagazine: New findings in mice have uncovered a crucial mechanism linking neuronal activity to mitochondrial function, researche….

RT @Ryohei_Neuro: Cool story about mitochondrial gene transcription regulation via CaMKII-CREB signaling, published in @ScienceMagazine .Co….

RT @Sharbeleid97: Happy Holidays from Laviv Lab! 🎉 We celebrated the season with our traditional Chanukah-Christmas party and a tour of bea….

RT @jinzhanglab: Looking for a fluorescent biosensor and don’t know where to start? Want a comprehensive overview of the field? Check out o….

Lastly, me and @ERSchreiter are chairing a session on cool FLIM related in vivo imaging applications, come and attend on Wednesday morning!

My talented student Tomer Kagan will present this work on Monday in poster board Z14 in #sfn2024, If you are interested please go and hear from him!.I would like to thank all the collaborators that helped us in this project and for my lab members for their hard work.

We found differential experience dependent changes in E and I cells! This highlights the need to explore PTEN signaling in a cell-specific manner, and to further explore the role of PTEN signaling during early brain development.

We also made a red sensor variant which allows one to co-express it with GFP based sensors and explore how other signaling protein interact with PTEN. I will end with our favorite and most exciting finding- we used dual color PTEN imaging in excitatory and Inhibitory cells.

For this we used a LOF mutation previously identified in a PTEN screen. This manipulation still maintains flexible conformational change of PTEN, but completely mitigates the effect on downstream signaling and cellular structure and function.

This approach allowed us to monitor PTEN activity in living cells- we identify an interesting association between PTEN loss of function mutants, and how they lead to structural instability of the protein. But- does our approach interfere with PTEN function?.

How? Luckily for us, nature already made PTEN an ideal substrate- since it undergoes a conformational transition upon activation, from closed to open state. We use this to tag PTEN with fluorescent proteins and show that this approach allows dynamic monitoring of PTEN activity.

How can we study PTEN? Despite its important role, there were no tools to directly measure PTEN activity in living cells, let alone in single cell resolution and in intact neuronal circuits. To circumvent this, we established a FRET based PTEN sensor, optimized for 2pFLIM.

Work in mouse models showed that both an increase and a decrease in PTEN levels has detrimental consequences on neuronal structure and function. In addition, we were intrigued by the work of @MarinLab who identified a crucial role for PTEN in E/I balance and early development.

Accordingly, numerus human cancers are associated with PTEN loss of function mutations. In the brain, mutations in PTEN are associated with severe epilepsy, autism and macrocephaly.

Why? PTEN is a vital phosphatase found in almost every cell, which is a key component and crucial role in growth factor signaling pathway. PTEN is a major inhibitor of cellular tropism, and thus is essential to protect cells from excessive growth and proliferation.