Seth Dickey

Seth Dickey

@dickeylab.bsky.social

131 followers114 following34 posts

Seth Dickey reposted

Lily McKnight
@lilymcknight.bsky.social

1/10 I am thrilled to announce my first first-author preprint, now live on bioRxiv! This focuses on my favorite little protein, GpsB, and its ties to fosfomycin resistance through phosphoregulation in S. aureus (a 🧵) www.biorxiv.org/content/10.6...

biorxiv.orgStaphylococcus aureus GpsB, Stk, and VraSR form a cell wall surveillance network to maintain cell envelope integrity and mediate antibiotic resistanceAntibiotic resistance is an alarming threat to public health worldwide. Specifically, drug-resistant Staphylococcus aureus remains a major contributor to global mortality. Therefore, in-depth understa...
Seth Dickey
@dickeylab.bsky.social

Final version is now available on mBio. journals.asm.org/doi/10.1128/...

journals.asm.orgBacteria synthesize a bacteriocin within the cell membrane | mBioBacteria have evolved numerous and diverse pathways to produce and secrete bacteriocins as weapons of bacterial warfare. These molecules are processed inside the cell and then transported across the bacterial membrane for secretion. We recently discovered the TMcins, a distinct class of bacteriocins found across gram-positive bacteria that contain a transmembrane helix and kill target bacteria by forming large pores. Using a Staphylococcus aureus strain that naturally produces TMcin, we show that TMcin production occurs in the cell membrane and reveal how bacteria process a membrane-spanning peptide in a lipid environment. This work expands our understanding of how bacteria produce antimicrobials and provides a model for discovering other membrane-localized natural products.
Seth Dickey
@dickeylab.bsky.social

Our dual-CRISPRi approach is programmable and scalable. We hope that it can help the field advance our understanding of S. aureus physiology, virulence, and microbial interactions. 10/10

Seth Dickey
@dickeylab.bsky.social

6.5/10 Cell division & membrane biosynthesis: silencing genes within fatty acid or phospholipid biosynthesis pathways suppressed the fitness defects of silencing a set of cell division genes. Interestingly, prior studies showed that disrupting these same genes often show large cell phenotypes.

Seth Dickey
@dickeylab.bsky.social

This led us to hypothesize that this enlargement of cells is because the balance between membrane biosynthesis and cell division has been perturbed, and that the excess production of membranes is contributing to the lethality of disrupting cell division. 7/10

Seth Dickey
@dickeylab.bsky.social

But getting large dual-CRISPRi libraries into MRSA was challenging because it is not a naturally competent. So @thesbhowmick.bsky.social meticulously optimized our electroporation protocol AND replaced the gene for the restriction enzyme hsdR with the cassette for inducible CRISPRi expression. 4/10

Seth Dickey
@dickeylab.bsky.social

Finding a genetic interaction (think suppressor mutations or synthetic lethal interactions) provides a deeper understanding of gene function and pathway interactions. A powerful tool, and we wanted a way to systematically uncover these en masse. 2/10

Seth Dickey
@dickeylab.bsky.social

Do you use artificial intelligence or machine learning in your research? Do you want to work in the vibrant DC metro area? Please consider applying for the open Assistant Professor position at UMD in College Park, Maryland. @umdscience.bsky.social umd.wd1.myworkdayjobs.com/UMCP/job/Uni...

umd.wd1.myworkdayjobs.comAssistant Professor-1Job Description Summary Organization's Summary Statement: Position Summary: The College of Agriculture and Natural Resources at the University of Maryland seeks candidates with expertise in utilizing ...
Seth Dickey
@dickeylab.bsky.social

How does TMcin remain soluble with a TM helix? We discovered two strategies: 1) as a monomer, TMcin has a loop with beta-strand structure that folds over the TM helix, making the whole peptide amphipathic, and 2) S. aureus PSMs peptides act as surfactants to further solubilize TMcins.

Seth Dickey
@dickeylab.bsky.social

We discovered the TMcin family in a rare cluster of #Staphylococcusaureus isolates but TMcin is found widely among Gram-positive bacteria. TMcin has broad activity against Gram-positive bacteria including (non-TMcin-producing) #MRSA and #VRE.

Seth Dickey
@dickeylab.bsky.social

Why would a bacteriocin possess a hydrophobic TM helix? We proposed that the TM helix allow TMcins to assemble stable and large beta-barrel pores anchored in cell membranes by the surrounding TM helices.

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Seth Dickey
@dickeylab.bsky.social

1/ We need a #UNSEENGOOD campaign. There's a lot of misinformation and cherry picking of bad apples (I'll own that mixed metaphor). I believe many people who don't interact with governments and organizations do not hear about the good work being done and this leads to reputational harm.

Seth Dickey
@dickeylab.bsky.social

2/ Organizations try to achieve this with communications departments. But they don't have the reach into the public who live different lives. Individuals who know the good being done - maybe because they're the ones doing it! - can simply provide examples on their social media platforms.

Seth Dickey
@dickeylab.bsky.social

3/ Hopefully this will make it clear to more what we stand to lose, and have lost, by the wholesale dismantling of government agencies and withdrawal from global collaborations.

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