Mark Brimble

Rational engineering of the P5 TRS-mimic site and REP78/68 start codon yields promoter variants that improve rAAV vector purity while maintaining high titers. During recombinant adeno-associated virus (rAAV) production, certain components of the manufacturing system can be encapsidated as unwanted nucleic acid contaminants. Prior work has established that t...

Congratulations to now graduated PhD student Stephen Winston for leading this study on rAAV contaminants.

This study shows that a mere 2 nucleotide modification to the (Rep78/68 driving) p5 promoter results in rAAV with equivalent titers but ~50-fold lower p5-derived contaminants. #genetherapy #AAV

Extinction and subsequent updating of innate fear responses to a visual looming stimulus rely on hippocampus-dependent mechanisms How does the brain balance innate responses with adaptive learning when reacting to threats? This study shows that repeated exposure to looming stimuli reduces innate defensive responses via hippocamp...

Starting 2026 with a thread a very recent manuscripts at Ryan Lab @tcddublin.bsky.social @tbsi-tcd.bsky.social

"Extinction and subsequent updating of innate fear responses to a visual looming stimulus rely on hippocampus-dependent mechanisms"
journals.plos.org/plosbiology/...

@PLOSBiology

TIRTL-seq: deep, quantitative and affordable paired TCR repertoire sequencing - Nature Methods TIRTL-seq is a high-throughput method for paired T cell receptor sequencing at the cohort scale.

Two complementary studies from our group out today: a therapeutic peptide vaccine trial for fibrolamellar carcinoma (FLC) & TIRTL-Seq, our robust method for deep quantitative paired TCR sequencing a🧵w/ @markyarchoan.bsky.social & @pogorely.bsky.social www.nature.com/articles/s41...

Patterns of c-Fos expression in the SC, PAG, and HPC reveal a loss of activity in the SC and PAG following extinction-updating but persistent activity of the vCA1. Top left: Engram labeling strategy. Bottom: TRAP2xAi32 mice underwent one of three types of behavioral paradigms; re-exposure (n = 6 mice) vs. no re-exposure (n = 6 mice), extinction (n = 7 mice) vs. innate (n = 8 mice), or updating (n = 11 mice) vs. innate (n = 8 mice). Mice were injected with 4-OHT to transiently induce c-Fos dependent EYFP upon first exposure to the looming stimulus, and later perfused 60 min following stimulus presentation at the end of the behavioral paradigm. Tolp right: Example histology from the SC, with an EYFP+c-Fos+ cell highlighted by the white arrow.

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

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!

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

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Citing article: 'In contrast to a pointless 2024 study done by barely literate and grotesquely unattractive authors [12]'

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

Plasticity of visual looming response reveals a dissociation of innate and learned components https://www.biorxiv.org/content/10.1101/2024.12.18.628938v1

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...

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!

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...

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.

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

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...

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

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

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

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