Tom McLean

Tom McLean

@tommclean.bsky.social

Structural Biochemist. Research Officer at WEHI. Future DECRA Fellow at Monash.

564 followers334 following28 posts

Tom McLean reposted

Matt Hutchings
@matthutchings.bsky.social

Fully funded PhD with me and @barriewilks.bsky.social - starting Oct 27. We identified a Streptomyces spore phase regulator, when we over express this it activates loads of silent antibiotic biosynthesis pathways. Come help us understand how! biodtp.norwichresearchpark.ac.uk/projects/ant...

biodtp.norwichresearchpark.ac.ukAntibiotic discovery in Streptomyces bacteria (HUTCHINGS_J27DTP) | Doctoral Training PartnershipAntimicrobial resistance in disease-causing bacteria represents a significant threat to global health. To address this, we urgently need to replenish the antibiotic discovery pipeline with new…

Tom McLean reposted

Tung Le
@tunglejic.bsky.social

Now published in JBac. Absolutely great publishing experience!!! Thank you to editors and reviewers.https://journals.asm.org/doi/10.1128/jb.00286-26 Another great one from @tommclean.bsky.social @johninnescentre.bsky.social @hbio-isp.bsky.social

journals.asm.orgTrbA binds and locks a sliding clamp KorB to repress transcription on multi-drug resistance plasmids | Journal of BacteriologyPrecise regulation of gene expression ensures gene products are produced at the right time and in the right amounts. Recent works uncovered a new mechanism of bacterial gene regulation based on a clamp sliding and locking in a multi-drug resistance plasmid, RK2. KorB functions as a CTP-dependent DNA-sliding clamp capable of traveling over a long genomic distance. Sliding KorB is captured and locked in place by a partner protein, KorA, forming a stable complex at target promoters to repress transcription. Here, we show that another RK2 regulator, TrbA, also uses this clamp sliding-locking mechanism, and identify an aromatic interface enabling TrbA-KorB-mediated transcriptional repression. Our findings show how a single sliding clamp integrates multiple partners to build a complex transcriptional regulatory network.
Tung Le@tunglejic.bsky.social

Here, @tommclean.bsky.social shows that another RK2 regulator, TrbA, likely also use this “clamp sliding-locking” mechanism to regulate gene expression. Interesting how a single sliding clamp might integrate multiple partners to potentially build a complex regulatory network... shorturl.at/YQJOI

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Tom McLean reposted

Leah McPhillips
@leahmcphillips.bsky.social

Excited to share this is now published in @narjournal.bsky.social 🎉 see the preprint thread below for a summary of our findings on plasmids with multiple partition systems using the Streptomyces plasmid SCP1 as a model! academic.oup.com/nar/article/...

academic.oup.comStable inheritance of the Streptomyces linear plasmid SCP1 by dual ParABS partition systemsAbstract. Low-copy-number plasmids often rely on dedicated maintenance mechanisms, such as partitioning systems, to ensure stable inheritance across genera
Leah McPhillips@leahmcphillips.bsky.social

📄 Delighted to share that the preprint of my main PhD work is out now! 👏 A huge thank you to everyone involved, @tommclean.bsky.social, Govind Chandra, Ngat Tran (both not on BlueSky) and especially my PhD supervisor @tunglejic.bsky.social 👏 🧵 below! www.biorxiv.org/content/10.6...

biorxiv.orgStable inheritance of the Streptomyces linear plasmid SCP1 by dual ParABS partition systemsLow-copy-number plasmids often rely on dedicated maintenance mechanisms, such as partitioning systems, to ensure stable inheritance across generations. These partition systems actively segregate siste...

Tom McLean reposted

Tung Le
@tunglejic.bsky.social

Replying to @tunglejic.bsky.social

KorB functions as a CTP-dependent DNA-sliding clamp traveling a long genomic distance. Sliding KorB is captured and locked in place by a partner protein, KorA, forming a stable A-B complex at target promoters to repress transcription.

Tom McLean reposted

Tung Le
@tunglejic.bsky.social

Sometimes ago Tom @tommclean.bsky.social uncovered a mechanism of bacterial gene regulation based on a clamp sliding and locking in a multi-drug resistance plasmid, RK2. www.nature.com/articles/s41...

nature.comKorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid - Nature MicrobiologyStructural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in th...

Tom McLean reposted

Jovana Kaljević ⬜️
@jovanakaljevic.bsky.social

My second postdoc paper in @tunglejic.bsky.social lab and two of my favorite things in the lab combined: ParB and killing bacteria. Thanks to everyone who helped make this project possible!

Tung Le@tunglejic.bsky.social

@biorxiv-microbiol.bsky.social Who knew ParB-CTPase fold can kill!!! A protein fold best known for segregating chromosomes…can be transformed into a potent antibacterial toxin in some plant and animal pathogens. www.biorxiv.org/content/10.6...

biorxiv.orgRepurposing a chromosome segregation ParB-CTPase fold into an ATPase toxin for contact-dependent growth inhibition in plant and animal pathogensBacterial competition drives the evolution of antibacterial mechanisms, yet how new activities arise remains poorly understood. A major route to innovation is the reuse of pre-existing genetic systems, whereby conserved protein modules are repurposed in new biological contexts to generate new capabilities. Here, we show that the ParB-CTPase fold, a conserved nucleotide-binding module best known for its role in chromosome segregation, can be functionally repurposed as an antibacterial toxin. We identify ToxB, a ParB-like domain embedded within the polymorphic toxin region of contact-dependent inhibition systems and show that it functions as a potent antibacterial effector. Structural and biochemical analyses reveal that ToxB retains the core architecture of the ParB-CTPase fold but lacks DNA-binding capability and preferentially binds ATP. This shift in nucleotide specificity underpins a distinct mode of action, in which ATP binding and hydrolysis trigger rapid nucleoid compaction, chromosome segregation defects, oxidative stress, cell chaining, and ultimately cell lysis. ToxB also exhibits toxic activity in plant cells, suggesting that it targets conserved cellular processes. Together, these findings provide direct experimental evidence that the ParB-NTPase fold is biologically versatile and can be repurposed for biological roles fundamentally distinct from its ancestral function in DNA segregation. ### Competing Interest Statement The authors have declared no competing interest. Wellcome Trust, https://ror.org/029chgv08, 221776/Z/2/Z, 227755/Z/23/Z Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/X01097X/1 Diamond Light Source, MX32728

Tom McLean reposted

Tung Le
@tunglejic.bsky.social

@biorxiv-microbiol.bsky.social Who knew ParB-CTPase fold can kill!!! A protein fold best known for segregating chromosomes…can be transformed into a potent antibacterial toxin in some plant and animal pathogens. www.biorxiv.org/content/10.6...

biorxiv.orgRepurposing a chromosome segregation ParB-CTPase fold into an ATPase toxin for contact-dependent growth inhibition in plant and animal pathogensBacterial competition drives the evolution of antibacterial mechanisms, yet how new activities arise remains poorly understood. A major route to innovation is the reuse of pre-existing genetic systems, whereby conserved protein modules are repurposed in new biological contexts to generate new capabilities. Here, we show that the ParB-CTPase fold, a conserved nucleotide-binding module best known for its role in chromosome segregation, can be functionally repurposed as an antibacterial toxin. We identify ToxB, a ParB-like domain embedded within the polymorphic toxin region of contact-dependent inhibition systems and show that it functions as a potent antibacterial effector. Structural and biochemical analyses reveal that ToxB retains the core architecture of the ParB-CTPase fold but lacks DNA-binding capability and preferentially binds ATP. This shift in nucleotide specificity underpins a distinct mode of action, in which ATP binding and hydrolysis trigger rapid nucleoid compaction, chromosome segregation defects, oxidative stress, cell chaining, and ultimately cell lysis. ToxB also exhibits toxic activity in plant cells, suggesting that it targets conserved cellular processes. Together, these findings provide direct experimental evidence that the ParB-NTPase fold is biologically versatile and can be repurposed for biological roles fundamentally distinct from its ancestral function in DNA segregation. ### Competing Interest Statement The authors have declared no competing interest. Wellcome Trust, https://ror.org/029chgv08, 221776/Z/2/Z, 227755/Z/23/Z Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/X01097X/1 Diamond Light Source, MX32728
Tom McLean
@tommclean.bsky.social

Reposting! We’re going to do some amazing science and have a lot of fun doing it!

Tom McLean@tommclean.bsky.social

Come do a PhD with me and @trevor-lithgow.bsky.social at @monashuniversity.bsky.social ! We’re at the leading edge of pathogen biology using cutting edge Cryo-EM and AI-driven genetic screens to uncover the mysteries of outer membrane biology. Reach out to me for a chat! macsys.org/phd-scholars...

macsys.orgPhD Scholarship at Monash University - MACSYSDo cutting-edge research at the intersection of cryo‑EM, genome-wide profiling, and AI-driven modelling. Work with world‑class cryo-EM/cryo-ET imaging and AI tools to discover how the dangerous bacter...
Tom McLean
@tommclean.bsky.social

Come do a PhD with me and @trevor-lithgow.bsky.social at @monashuniversity.bsky.social ! We’re at the leading edge of pathogen biology using cutting edge Cryo-EM and AI-driven genetic screens to uncover the mysteries of outer membrane biology. Reach out to me for a chat! macsys.org/phd-scholars...

macsys.orgPhD Scholarship at Monash University - MACSYSDo cutting-edge research at the intersection of cryo‑EM, genome-wide profiling, and AI-driven modelling. Work with world‑class cryo-EM/cryo-ET imaging and AI tools to discover how the dangerous bacter...

Tom McLean reposted

Matt Hutchings
@matthutchings.bsky.social

First results chapter from Kelly-Rose Tulley’s PhD is published. It was a great team effort to get this finished. This work supports previous results on S. coelicolor OrrA and suggests its function is highly conserved. #microsky #streptomyces 1/2

bioRxiv Microbiology@biorxiv-microbiol.bsky.social

Defining the OrrA regulon and its role in development and antibiotic production in Streptomyces venezuelae NRRL B-65442 https://www.biorxiv.org/content/10.64898/2026.01.30.702861v1

Tom McLean
@tommclean.bsky.social

Too excited by the science to include the link to the paper! Here it is: journals.asm.org/doi/10.1128/...

journals.asm.orgThe conserved two-component systems CutRS and CssRS control the protein secretion stress response in Streptomyces | mBioStreptomyces bacteria are the primary source of clinically useful antibiotics. While many two-component systems have been linked to antibiotic biosynthesis in Streptomyces species, few have been well ...
Tom McLean@tommclean.bsky.social

Delighted to see the main work from my PhD finally published in @mbio.bsky.social! It all started with the observation that deleting the cutRS two-component system in S. venezuelae caused this amazing explorer phenotype in the presence of glucose. But what was going on?! (1/n)

Tom McLean
@tommclean.bsky.social

Delighted to see the main work from my PhD finally published in @mbio.bsky.social! It all started with the observation that deleting the cutRS two-component system in S. venezuelae caused this amazing explorer phenotype in the presence of glucose. But what was going on?! (1/n)

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Tom McLean
@tommclean.bsky.social

This leads to the activation of HtrA-family dual function chaperone/proteases that can act to restore the cell to homeostasis! To our knowledge, this is the first proposal of a sensing model for a bacterial secretion or envelope stress response system! (6/7)

Tom McLean
@tommclean.bsky.social

Delighted to see the main work from my PhD finally published in @mbio.bsky.social! It all started with the observation that deleting the cutRS two-component system in S. venezuelae caused this amazing explorer phenotype in the presence of glucose. But what was going on?! (1/n)

View full thread
Tom McLean
@tommclean.bsky.social

Finally, through ChIP-seq, TMT-proteomics and qRT-PCR we managed to link it all. Together with CssRS, CutRS detect secretion stress through the formation (or lack thereof) of the conserved disulfide bond in their sensor kinase sensor domain. (5/n)

Tom McLean
@tommclean.bsky.social

Delighted to see the main work from my PhD finally published in @mbio.bsky.social! It all started with the observation that deleting the cutRS two-component system in S. venezuelae caused this amazing explorer phenotype in the presence of glucose. But what was going on?! (1/n)

Tom McLean
@tommclean.bsky.social

This mutant also overproduced the antibiotic chloramphenicol, leading to a very potent anti-Gram-postitive activity on plate assays. However, this still didn't give us any clues as to what linked CutRS to the phenotype. (2/n)

Tom McLean
@tommclean.bsky.social

My favourite piece of data in the whole paper came after we quantified the biomass difference between the WT and ∆cutRS mutant on glucose media, showing it is around 4x more massive. It also uses up all the glucose in the plate, close to gram, in just 9 days! (3/n)

Tom McLean reposted

Leah McPhillips
@leahmcphillips.bsky.social

📄 Delighted to share that the preprint of my main PhD work is out now! 👏 A huge thank you to everyone involved, @tommclean.bsky.social, Govind Chandra, Ngat Tran (both not on BlueSky) and especially my PhD supervisor @tunglejic.bsky.social 👏 🧵 below! www.biorxiv.org/content/10.6...

biorxiv.orgStable inheritance of the Streptomyces linear plasmid SCP1 by dual ParABS partition systemsLow-copy-number plasmids often rely on dedicated maintenance mechanisms, such as partitioning systems, to ensure stable inheritance across generations. These partition systems actively segregate siste...

Tom McLean reposted

Jovana Kaljević ⬜️
@jovanakaljevic.bsky.social

Our preprint is now published in PNAS! This came together thanks to a great collaboration with Antoine Hocher and a strong team effort from the Le Lab. Thank you to the reviewers and to everyone who helped improve it. I hope ParB aficionados will enjoy it. www.pnas.org/doi/10.1073/...

pnas.orgVersatile NTP recognition and domain fusions expand the functional repertoire of the ParB-CTPase fold beyond chromosome segregation | PNASNucleotide triphosphate (NTP)-dependent molecular switches regulate essential cellular processes by cycling between active and inactive states thro...

Tom McLean reposted

Ben Long
@botbml.bsky.social

#straya Bin Chicken: targeted metagenomic coassembly for the efficient recovery of novel genomes. www.nature.com/articles/s41...

nature.comBin Chicken: targeted metagenomic coassembly for the efficient recovery of novel genomes - Nature MethodsBy developing a strategy of metagenomic coassembly and prioritizing divergent marker gene sequences, Bin Chicken efficiently recovers more than 77,000 microbial genomes with high novel diversity, ther...

Tom McLean reposted

Harmit Singh Malik
@harmitmalik.bsky.social

When people celebrate the individual genius of folks in science, they should also mourn the collective loss of genius of folks who were actively discouraged or disadvantaged from a career in science because of the same person(s)

Tom McLean reposted

Tung Le
@tunglejic.bsky.social

new preprint from our group & Antoine Hocher: www.biorxiv.org/content/10.1... A fantastic collaboration with Antoine, with Jovana Kaljevic' initiated the collaboration and drives the project.

biorxiv.orgVersatile NTP recognition and domain fusions expand the functional repertoire of the ParB-CTPase fold beyond chromosome segregationNucleotide triphosphate (NTP)-dependent molecular switches regulate essential cellular processes by cycling between active and inactive states through nucleotide binding and hydrolysis. These mechanis...
Tom McLean
@tommclean.bsky.social

After 8 wonderful years in Norwich, 3 at UEA and 5 at the JIC it’s time to say goodbye. I will miss each and every amazing person I’ve had the pleasure of working with or meeting here. It truly is a fine city.

Tom McLean
@tommclean.bsky.social

Check out our lab's new work on a CTP-independent ParABS system. Some fantastic work from Kirill et al!

Tung Le@tunglejic.bsky.social

Finally published! Many thanks to the reviewers and editor whose comments & suggestions improved this work significantly more than the first preprint version!!! www.pnas.org/doi/10.1073/...

pnas.orgExpanding the diversity of bacterial DNA partitioning: A CTP-independent ParABS system for plasmid partitioning in Streptomyces | PNASThe ATP- and CTP-dependent ParA-ParB-parS segrosome is a macromolecular complex that segregates chromosomes/plasmids in most bacterial species. CTP...
Tom McLean
@tommclean.bsky.social

Have a read of this simply phenomenal work on the weird and wonderful GTAs from star Fellow (and office mate) Emma Banks et al

Tung Le@tunglejic.bsky.social

1/ Excited to share our latest work on gene transfer agents (GTAs) in Caulobacter crescentus, led by Emma Banks in collaboration with Pavol Bardy and Mai Nguyen from York!!! See a brief thread below. shorturl.at/o6S1w

shorturl.atA bacterial CARD-NLR immune system controls the release of gene transfer agentsBacteria have evolved a wide array of immune systems to detect and defend against external threats including mobile genetic elements (MGEs) such as bacteriophages, plasmids, and transposons. MGEs are ...

Tom McLean reposted

Trevor Lithgow
@trevor-lithgow.bsky.social

"That telomere phages are so prevalent means that they are a selective force, one that we know little about. We now want to understand how the telomere-toxin is secreted and also understand how this ‘telocin’ wheedles its way into unsuspecting bacterial neighbors” www.science.org/doi/10.1126/...

science.orgTelomere bacteriophages are widespread and equip their bacterial hosts with potent interbacterial weaponsKlebsiella host strains infected with telomere phages can grow to be the dominant lineage in mixed populations.
Tom McLean
@tommclean.bsky.social

The paper is now live: academic.oup.com/mbe/article/... Absolutely delighted to play a role in this fascinating story!

academic.oup.comEvolution of a Plasmid Regulatory Circuit Ameliorates Plasmid Fitness CostAbstract. Plasmids promote adaptation of bacteria by facilitating horizontal transfer of diverse genes, notably those conferring antibiotic resistance. Som
Chris Thomas@chrismthomas.bsky.social

The second great paper concerns the discovery in Eva Top's group that an enigmatic protein encoded by IncP-1beta plasmids modulates the IncP-1 circuitry in E. coli to make the plasmid a burden in this host: Elg et al recently accepted in Molecular Biology and Evolution doi.org/10.1093/molb...

doi.orgpendingpublicationsPending Publication
Tom McLean
@tommclean.bsky.social

Almost 8 years after starting this project finally happy to share the main research from my PhD! Couldn't have done it without the amazing help from @ainsley-beaton.bsky.social! We untangled a fascinating new redox sensor with the most extraordinary growth phenotype (I'm biased) in Streptomyces!

Matt Hutchings@matthutchings.bsky.social

Very happy to share this work led by @tommclean.bsky.social and @ainsley-beaton.bsky.social. The conserved Streptomyces sensor kinase CutS senses disulphide bond formation outside the cell. If it fails CutS activates CutR which switches on production of foldase HtrA3 www.biorxiv.org/content/10.1...

biorxiv.orgExtracellular redox sensors control the protein secretion stress response in StreptomycesTranslocating unfolded polypeptides across membranes is essential in all domains of life and in bacteria requires the conserved Sec machinery and ATP. Bacterial Sec substrates fold outside the cell an...

Tom McLean reposted

Ainsley Beaton
@ainsley-beaton.bsky.social

Further insight into how CutRS functions in Streptomyces and some thoughts on how its redox state detection via conserved dual cysteine residues in the extra cellular domain of a sensor kinase may be present in almost all bacteria @tommclean.bsky.social @matthutchings.bsky.social

bioRxivpreprint@biorxivpreprint.bsky.social

Extracellular redox sensors control the protein secretion stress response in Streptomyces https://www.biorxiv.org/content/10.1101/2025.03.20.644377v1

Tom McLean reposted

Matt Hutchings
@matthutchings.bsky.social

Very happy to share this work led by @tommclean.bsky.social and @ainsley-beaton.bsky.social. The conserved Streptomyces sensor kinase CutS senses disulphide bond formation outside the cell. If it fails CutS activates CutR which switches on production of foldase HtrA3 www.biorxiv.org/content/10.1...

biorxiv.orgExtracellular redox sensors control the protein secretion stress response in StreptomycesTranslocating unfolded polypeptides across membranes is essential in all domains of life and in bacteria requires the conserved Sec machinery and ATP. Bacterial Sec substrates fold outside the cell an...

Tom McLean reposted

Matt Hutchings
@matthutchings.bsky.social

Redox control of antibiotic biosynthesis in Streptomyces. Remarkable work led by @katienoble241.bsky.social and Rebecca Devine demonstrates why antibiotic biosynthesis is often switched on in solid cultures and off in liquid. www.biorxiv.org/content/10.1...

biorxiv.orgRedox control of antibiotic biosynthesisStreptomyces bacteria make diverse specialised metabolites that form the basis of ~55% of clinically used antibiotics. Despite this, only 3% of their encoded specialised metabolites have been matched ...

Tom McLean reposted

Tung Le
@tunglejic.bsky.social

Cool “Behind the paper” article on our recent KorB-KorA sliding clamp-locking clamp story. I remember Chris Thomas and Lewis Bingle (Birmingham) taught me about these proteins when I was an undergrad, and I kept remembering they said the mechanism was not clear!!! www.nature.com/articles/s41...

nature.comSliding clamp protein enables long-range gene silencing in a bacterial plasmid - Nature MicrobiologyLong-distance gene regulation is uncommon in bacteria, and its molecular mechanisms are unclear. Using a combination of structural, biochemical and single-molecule techniques, researchers revealed tha...

Tom McLean reposted

Nature Microbiology
@natmicrobiol.nature.com

OUT NOW: KorB is a DNA clamp which slides along DNA to mediate long-range gene silencing upon interaction with the clamp-locking KorA protein by Tung Le & co @johninnescentre.bsky.social www.nature.com/articles/s41...

nature.comKorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid - Nature MicrobiologyStructural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in th...
Tom McLean
@tommclean.bsky.social

Super excited to share the peer-reviewed version of the KorAB paper. Amazing to work such talented collaborators and thanks to the reviewers for making the work even better! www.nature.com/articles/s41...

nature.comKorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid - Nature MicrobiologyStructural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in th...

Tom McLean reposted

Timothée Poisot
@ctrlalttim.com

New paper in PLOS Biol with @graciellehigino.bsky.social et al.: "Postdoctoral scientists are mentors, and it is time to recognize their work". We argue that ensuring that post-docs receive proper credit for ALL their labour would benefit all academia.

journals.plos.orgPostdoctoral scientists are mentors, and it is time to recognize their workPost-doctoral scientists are effective mentors for graduate students. This Perspective discusses how failures to properly credit them for this role has negative consequence for everyone and suggests p...

Tom McLean reposted

Géraldine Laloux
@lalouxlab.bsky.social

First post in this place 💙our last story on the #ParABS system and the unique behaviour of #ParB during the #Bdellovibrio cell cycle is now alive at #PLOSGenetics! We love the revised version (thanks to the 3 super reviewers & great editorial advice). Read it here dx.plos.org/10.1371/jour...

dx.plos.orgCell cycle-dependent organization of a bacterial centromere through multi-layered regulation of the ...Author summary The precise distribution of genetic material to the progeny is essential for all living organisms, and the ParABS system is critical for this process in most bacteria. Our study provide...