Mark Brimble
brimble.bsky.social
Mark Brimble
@brimble.bsky.social
AAV Gene therapy researcher + below average ultrarunner. 2022 ASGCT CDA. 2023-2028 CFF postdoc to faculty grant. Thomas Lab
Reposted by Mark Brimble
How do we balance innate responses & adaptive learning when reacting to threats? @tjryan.bsky.social &co show that repeated exposure to looming stimuli reduces innate defensive responses via #hippocampal modulation, revealing a vCA1 engram needed for learned #fear @plosbiology.org 🧪 plos.io/4pNSnNp
September 29, 2025 at 4:56 PM
So glad to see this story ready to share as a preprint. This was a really fun collaboration and a stunning finding with big potential implications. Congrats Iva!
New preprint! In 2014, we showed that histone variants are new regulators of memory and ever since, we wondered if histone H2A.Z contributes to Alzheimer's. Using human brains and 5xFAD mice, we found that it depends on if you're male or female. Summary below. www.biorxiv.org/cgi/content/...
Opposing effects of H2A.Z on memory, transcription and pathology in male and female Alzheimer's disease mice and patients
Alzheimer's disease (AD) is a devastating neurodegenerative disease that disproportionately impacts women, but underlying mechanisms for sex-divergent outcomes are unknown. Here, we show that the hist...
www.biorxiv.org
June 2, 2025 at 12:17 PM
Reposted by Mark Brimble
Opposing effects of H2A.Z on memory, transcription and pathology in male and female Alzheimer's disease mice and patients https://www.biorxiv.org/content/10.1101/2025.05.28.656659v1
June 1, 2025 at 5:15 PM
*You have a new citation, click here to view*

Citing article: 'In contrast to a pointless 2024 study done by barely literate and grotesquely unattractive authors [12]'
March 27, 2025 at 7:47 PM
Had an excellent meeting with staff from @slotkin.senate.gov about the importance of supporting robust funding for Biomedical research. @immunologyaai.bsky.social and the community appreciate your support #PPFPHillDay
March 5, 2025 at 5:51 PM
Reposted by Mark Brimble
Plasticity of visual looming response reveals a dissociation of innate and learned components https://www.biorxiv.org/content/10.1101/2024.12.18.628938v1
December 29, 2024 at 11:15 AM
Reposted by Mark Brimble
Durable lymphocyte subset elimination upon a single dose of AAV-delivered depletion antibody dissects immune control of chronic viral infection
@cp-immunity.bsky.social
www.cell.com/immunity/ful...
December 26, 2024 at 6:16 PM
An amazing collaboration to be a part of: We helped @gisellavetere.bsky.social & @clementpouget.bsky.social simultaneously deliver 3 AAV constructs to Ca1 neurons.

What they then acheived blew me away - the tagging of cells recruited in memory encoding with a temporal resolution of mere seconds!
Our preprint of my PhD’s work in @gisellavetere.bsky.social lab is finally out on BiorXiv: doi.org/10.1101/2024..., and I’m so excited to share it! If you’ve ever wondered about reconciling engram manipulation experiments and neuronal activity during encoding, you’re on the right thread! 1/14
Deconstruction of a memory engram reveals distinct ensembles recruited at learning
How are associative memories formed? Which cells represent a memory, and when are they engaged? By visualizing and tagging cells based on their calcium influx with unparalleled temporal precision, we ...
doi.org
December 13, 2024 at 5:51 PM
Reposted by Mark Brimble
We keep improving TIRTL-seq, see the updated preprint (www.biorxiv.org/content/10.1...)! New additions include: a manual 96-well protocol, code and raw data now available, and successful in vitro validation of EBV and SARS-CoV-2 TCRs.
TIRTL-seq: Deep, quantitative, and affordable paired TCR repertoire sequencing
α/β T cells are key players in adaptive immunity. The specificity of T cells is determined by the sequences of the hypervariable T cell receptor (TCR) α and β chains. Although bulk TCR sequencing offe...
www.biorxiv.org
November 26, 2024 at 7:42 PM
Reposted by Mark Brimble
New starter pack for all people interested in Gene Editing & Gene Therapy 🧬✂️ including Tools & Delivery|CRISPR-Cas|Zinc finger nucleases|Viral vectors|Non-viral delivery methods

go.bsky.app/8R4dVez
November 20, 2024 at 9:12 PM
Glad to get the chance to write this commentary on a recent paper by Penaud Budloo et al that found miRNA contaminants within purified rAAV preparations.

An interesting and unique AAV vector purity study
Non-encapsidated miRNA contaminants found in AAV preparations
Adeno-associated virus (AAV) has been in clinical use for gene therapy applications for over a decade, with 6 FDA-approved drug products at the time of writing.1 However, this vector is manufactured i...
www.cell.com
November 19, 2024 at 7:04 PM
Reposted by Mark Brimble
TCR repertoire dream: decoding immune status by sequencing TCRs. Problems: 1) Need paired TCRab 2) Interesting T cell clones are often VERY small. Our solution: TIRTL-seq 🐢Deep, quantitative, & affordable paired TCR repertoire sequencing🧵 https://www.biorxiv.org/content/10.1101/2024.09.16.613345v1
September 23, 2024 at 5:28 PM
Not only is the alternative histone H2A.Z.1 involved in memory formation, this role is lysine acetylation dependent!

Thrilled to have contributed to this great work from Iva Zovkic's lab
Role of the histone variant H2A.Z.1 in memory, transcription, and alternative splicing is mediated by lysine modification - Neuropsychopharmacology
Neuropsychopharmacology - Role of the histone variant H2A.Z.1 in memory, transcription, and alternative splicing is mediated by lysine modification
www.nature.com
November 19, 2024 at 7:04 PM