P.S. the Dr. title is their addition, not mine! My application did state that I am still a PhD student - thesis submitted; viva to come in January.

I'll be following up on some findings from my PhD regarding a potential physiological role of Huntingtin. With the recent incredibly exciting success of Huntingtin-targeting genetic therapies for Huntington's disease, understanding these physiological roles is even more important!

Not just a typo I'm afraid! The paper is about the cAMP-CREB axis, but their cAMP measurements are by qPCR (which obviously isn't possible for a small molecule).
It also gets better: the unrelated CAMP isn't even expressed in the cell type they are working with!

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

That's embarrassing 🤣 thank you!

Would love to join!

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