Great new paper highlighting @jenniferepalmer.bsky.social 's PhD work: www.cimr.cam.ac.uk/research-adv...

Very grateful to all co-authors, including our collaborators Ryan O'Rourke and Alvin Huang. Also extremely grateful to the @ukdri.ac.uk for research funding and support, and the Cambridge Trust, @royalsocietynz.bsky.social and Rutherford foundation for supporting my PhD

We already knew that autophagosome closure and release are coordinated (see Puri et al 2023) but we didn't understand how. Our work highlights the importance of studying disease-associated proteins - both to understand disease and to learn more about the physiological regulation of key processes.

We also found that BIN1 interacts with the ESCRT-III complex at phagophores prior to their closure. This prevents the release of open phagophores by DNM2. Once membrane closure is complete, ESCRT-III disassembles, releasing BIN1 and enabling DNM2-mediated release of the closed autophagosome

Thus, we propose that one way BIN1 might affect the risk of Alzheimer's disease is by impairing microglial autophagy. Mechanistically, the autophagy impairment is due to the inhibition of a DNM2-dependent scission step that releases newly formed autophagosomes from the recycling endosome.

So, how does increased microglial BIN1 increase the risk of Alzheimer's disease? We find that BIN1 inhibits autophagy. Previous research has linked microglial autophagy impairment to exacerbated neurodegeneration through altered phagocytosis and cytokine secretion.

Genetic variants in a myeloid-specific enhancer for BIN1 increase BIN1 expression in microglia, but not in other brain cells. Existing work links BIN1 to tau, endocytosis, and synaptic vesicle processes. But, the microglial-expressed isoforms lack the CLAP domain required for endocytic functions

The first research article from my PhD is out now in @cp-cellreports.bsky.social
Read on to hear about how increased BIN1 in microglia impairs autophagy, and a physiological function for BIN1 in coordinating the closure and release of newly-formed autophagosomes
www.cell.com/cell-reports...

What a fantastic day at #CambridgeFestival!!

@thecimr.bsky.social contributed again to this years Cambridge Festival at the Biomedical Campus. Thanks to all amazing colleagues from @thecimr.bsky.social, @cambridgeuni.bsky.social making this event run!!

More here: www.lautenschlager-lab.com/blog

Great fun today!

An interview for the @aotearoabrainproj.bsky.social by my previous classmate (and now Dr!!!) Lily Bentall. One of the standouts about the NZ neuroscience community to me is how connected and supportive it is - awesome mahi from the ABP! www.aotearoabrainproject.nz/news/flag-re...

Great review on neuronal autophagy and synapses: www.cell.com/neuron/fullt...

Hello! Although we are still in the other place, this will become our main social media feed. We're part of the University of Cambridge Clinical School
Cell biology, molecular mechanisms of human disease

Great day at #RAREfest24 talking with people living with rare diseases, their families, other scientists, and artists (and playing with microscopes and clay of course!). My favourite things from today: these artworks about Prion disease by Emily Jolley, and the feelings of hope shared by many

That's embarrassing 🤣 thank you!

Would love to join!

🧠Re-sharing this as the list is growing. 🌲
Let me know if I've left you out - or if you think I should add someone! 🧠

go.bsky.app/S6FfsTp

Cell bio & autophagy here 👋 there are a few cell biology-related starter packs, but I agree, it takes time and effort to build community here! The starter pack searchable list (blueskydirectory.com/starter-pack...) is helpful

To celebrate the move to Bluesky, here is our recent review on autophagy, ageing, and age-related neurodegeneration: www.cell.com/neuron/fullt...