Maslowski MMIMiC Lab

Great news! Abstract deadline is extended till next Friday, 3rd October!

Interested in host-microbe interactions and how we can apply findings to develop immunotherapies? The come join us for an exciting workshop in October @cruk-si.bsky.social
www.crukscotlandinstitute.ac.uk/events/125-s...

If you are UK-based and working on any aspect of microbiomes (human, plant, insect, soil, animal, ...), please do sign up to Microbiome-Net for details of networking, funding and training opportunities.

forms.office.com/pages/respon...

Cancer research ‘set back years’ as visa fees drive scien... With vital studies being shelved and foreign experts turning down jobs, leading charity urges ministers to act

“High visa fees are putting off some of the world’s most talented scientists from coming to the UK,” said Foulkes, with “We need to be able to compete for the world’s best scientists.” research institutes forced to divert funds from labs to pay fees.”
observer.co.uk/news/nationa...

Congratulations Cassie and team! Great to see it out, well done.

And we did make it! Amazing day! We’re so grateful to all the friends, family and colleagues who helped us reach our fundraising goal!

Extremely hot #BigHike

We’re off on the #BigHike! Beautiful day for it, raising money for @cancerresearchuk.org
fundraise.cancerresearchuk.org/page/kendles...

@cancerresearchuk.org

Bugs against Cancer team Cancer is happening right now, which is why we're fundraising right now for Cancer Research UK. There’s no time to lose! Donate today and help bring forward the day when all cancers are cured. Donatin...

The team is swapping pipettes for hiking boots to take part in the CRUK Big Hike in the Trossachs in a couple of weeks' time. We'd be grateful for any contributions to the CRUK who fund us and so much vital cancer research! fundraise.cancerresearchuk.org/team/bugs-ag...

Happy big birthday @roscobacterium.bsky.social ! Celebrated in style at lab meeting with Tiramisu made by @celespin.bsky.social 😋

We are incredibly proud to announce that the School of Cancer Sciences has been awarded the prestigious Athena Swan Gold Award ⭐

An exciting opportunity to work on gamma deltas in breast cancer👇🏻. A great lab in a great institute!

Summary of some our activities by our very own @roscobacterium.bsky.social for world cancer day.

Fighting fire with fire: could Salmonella treat bowel cancer? - Cancer Research UK - Cancer News Our researchers are modifying Salmonella into a treatment that works with the immune system to attack bowel cancer from two sides at once.

Nice write up by CRUK (yet to join Bluesky!) on our recent work! @cruk-si.bsky.social
news.cancerresearchuk.org/2025/01/23/f...

Thanks! ☺️

a black and white drawing of a cat with the words `` thank you '' written above it . ALT: a black and white drawing of a cat with the words `` thank you '' written above it .

Thanks if you made it this far! This has been a really fun project with lots of twists and turns. Do check it out if it takes your interest! A lot of hard work from Alastair and super collaboration with @bendinglab.bsky.social @sarahdimeloe.bsky.social and thanks to the input from all authors 12/12

And this mechanism also fits for E.coli. EV5 shows E. coli Nissle, another popular probiotic and BCT vector also causes aborted T cell activation - so caution I guess if you wanna couple this with checkpoint blockade (as there are no checkpoints to block if T cells are disabled). 11/12

Before you go - a couple of fun side notes from the sup figures. FIRST, we could have missed this phenotype without the Timer system, EV1 shows comparison with the Nr4a1-GFP and Nr4a1-Timer. GFP gives the impression all is fine bc it sticks around-don't get the info of seeing it turned off. 10/12

What about back in vivo, can it still work? Well the Asnase-deficient STm still controls tumour growth, despite losing some effect on tumour stemness. SO, bringing T cells back on board is a good thing. That's where this story ends, for now! Much to unpick still! 9/12

...not quite. Would have been a neat bundle of joy as is, but then we wondered about the effect on the tumour cell...so we looked and yup, Asn depletion is also reducing tumour c-myc...but that's a good thing! Use of the Asnase-KO STm restores tumour c-Myc and 'stemness' 8/12

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After a few rabbit holes we finally pin it down to ASPARAGINE! STm express an asparaginase (as do E. coli), and gobble up asparagine in the TME. T cells REALLY need it (c-myc really needs it). So we remove Asnase and T cells now activate beautifully - JOB DONE?! 7/12

What's going on? TCR signal transduction is fine...mTOR/AKT are fine. Finally (took us a while!) we found c-myc was the culprit - T cells in presence of STm TCM could not upreg protein levels required for metabolic switch, so activation aborts....cool....but why? 6/12

Turn to RNAseq and by 16hrs stim CD4's have failed metabolic reprogramming -> check functionally by seahorse - yep T cells can't upreg glycolysis, oxphos also impaired. This occurs even with just the conditioned medium of STm-infected org's, so it's soluble 5/12

T cells are dysfunctional. IFNy doesn't correlate with TCR activity, ↓PD-1 & ↓ polyfunctionality. Tumour organoid--T cell co-culture shows arrested TCR signalling after 24-48 hrs aCD3/CD28 stim. What is going on? 4/12

We used TCR reporter mice (Nr4a3-Timer) crossed with IFNy and induced colonic tumours with AOM/DSS (previous pub Mackie, JCI Insight shows efficacy of attenuated STm in this model). Like others we see ↑CD4 and CD8 infiltration and ↑IFNy...BUT...3/12

a white cat is sitting on a box with the words `` why why '' written above it . ALT: a white cat is sitting on a box with the words `` why why '' written above it .

20 years of literature tells us Salmonella (STm) cancer therapy works just fine (in mice) if there are no T cells - yet many (including us) are looking at ways to target T cells alongside STm. We set out to find out WHY! 2/12

Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity | EMBO Molecular Medicine imageimageAttenuated Salmonella show promise as cancer therapeutics, yet T cells play no role in efficacy, limiting combined checkpoint blockade therapies or induction of immune memory. Improving T ce...

Finally! A🧵for our recent paper 🎉 #Immunosky #microsky #metabolism www.embopress.org/doi/full/10..... A cool host-microbe story, with some fun TCR signalling and metabolism so a bit for everybody. (quite long, so get some popcorn!) 1/12

First off, we do see ↑CD4&8 infiltration and ↑IFNy...but there's something not quite right...IFNy does not correlate with TCR engagement, and we see poor polyfunctionality.

We used Nr4a1-Timer TCR reporter mice crossed with an IFNy reporter - then induced colonic tumours using AOM/DSS (prev pub showing STm reduce tumour burden in this model).