Linda Sinclair

Linda Sinclair

@lindavsinclair.bsky.social

Immunologist, working with Cantrell Lab. Interested in LOTS - focused on nutrient and metabolic control of the immune system. (opinions are my own)

2.4K followers581 following39 posts

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Linda Sinclair
@lindavsinclair.bsky.social

I am overjoyed to present our latest paper on Autophagy in CD8 Tcells! www.nature.com/articles/s41... It was, as all ‘sciencing’ is, a huge team effort. I will try to do it some justice in the following thread 😊 1/n @cantrell-lab.bsky.social @immpres.bsky.social @ajmhowden.bsky.social

nature.comAutophagy repression by antigen and cytokines shapes mitochondrial, migration and effector machinery in CD8 T cells - Nature ImmunologySinclair et al. combine quantitative proteomics and an autophagy flux reporter to map autophagy substrates and triggers during CD8 T cell differentiation. Proteins degraded and fueled by autophagy in ...

Linda Sinclair reposted

David Finlay
@davidfinlaytcd.bsky.social

****2-NBDG does not measure glucose uptake**** Just your regular reminder of this fact 😁. See the rigorous proof of this fact in @lindavsinclair.bsky.social 2020 paper. This paper was 6 years ago!! Stop using 2NBDG to measure glucose uptake already 🙄 pmc.ncbi.nlm.nih.gov/articles/PMC...

pmc.ncbi.nlm.nih.govSingle Cell Glucose Uptake Assays: A Cautionary TaleAssays to monitor the metabolic state or nutrient uptake capacity of immune cells at a single cell level are increasingly in demand. One assay, used by many immunologists, employs 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose ...

Linda Sinclair reposted

drakesmith-lab.bsky.social
@drakesmith-lab.bsky.social

2 new efforts: from Megan Teh on metabolism of CD8 Tcells in iron deficiency and why they love aspartate (+ @sarahdimeloe.bsky.social @lindavsinclair.bsky.social); & reviewing the strong influence of iron on immunity @joefrost.bsky.social www.nature.com/articles/s41... www.nature.com/articles/s41...

nature.comIron and the immune system - Nature Reviews ImmunologyIron is crucial for cellular metabolism, but its availability varies greatly within and between individuals and populations. This Review highlights how iron regulates innate and adaptive cellular and ...

Linda Sinclair reposted

Sparwasser Lab
@timsparwasser.bsky.social

Special issue Immunometabolism and Beyond: from Liver to Brain! European Journal of Immunology Article types: reviews and research articles Submission deadline 1 November 2025 Thanks to Nadja, Matteo and Bin for this wonderful opportunity! #immunometabolism #EJI #CRC1292 #CRC355 #CRC156 #FZI

Linda Sinclair reposted

Masahiro Ono @ Tocky Lab
@monotockylab.bsky.social

What if Tregs are not a separate lineage, but part of spontaneously activated T cells? In this work, we integrate this idea with our recent findings: Adult T cell leukemia (ATL) is not 'Treg cancer', challenging the current concept of Treg as a distinct entity.🧵(1/4) academic.oup.com/discovimmuno...

academic.oup.comSpectrum of Treg and self-reactive T cells: single cell perspectives from old friend HTLV-1Summary. Despite extensive regulatory T cell (Treg) research, fundamental questions on in vivo dynamics remain to be answered. The current study aims to di
Linda Sinclair
@lindavsinclair.bsky.social

Our review on Protein Synthesis and Metabolism in T cells is out @annualreviews.bsky.social @cantrell-lab.bsky.social Protein Synthesis and Metabolism in T Cells #proteomics #immunometabolism #Tcells www.annualreviews.org/content/jour...

annualreviews.orgProtein Synthesis and Metabolism in T Cells | Annual ReviewsT lymphocytes are essential for immune responses to pathogens and tumors. Their ability to rapidly clonally expand and differentiate to effector cells following infection, and then to curb effector fu...

Linda Sinclair reposted

Derek Mann
@damann1.bsky.social

Very excited to be just a weekend away from this UK conference on neutrophil biology that we are hosting at Newcastle. It includes international keynotes but most important the majority of speakers are early career researchers. #immunology #inflammation #neutrophils #humandisease

Linda Sinclair reposted

Emma Slack
@mucosalimmunology.bsky.social

Two weeks left to apply for a postdoc position with the Slack group! Please spread the word!

Emma Slack@mucosalimmunology.bsky.social

Interested in microbial #metabolism, #mucosalbiology and #UTI? Then check out the open postdoctoral position in the Mucosal Immunology Group at ETH Zurich! NB: All applications must go via the ETH job portal: www.jobs.ethz.ch/job/view/JOP... Closing date: 24th Feburary 🧪🧫🔬

jobs.ethz.chPostdoctoral researcher –Understanding bacterial metabolism in the urinary tract

Linda Sinclair reposted

Perona Lab, Edinburgh, UK
@peronalab.bsky.social

I'm very pleased to have two lab positions open this week, to join our team looking at immune regulation in infection and co-infection. We're especially interested in tissue-based immunity, cytokine regulation and immune metabolism. Join us! Postdoc (3y) and research technician (12mo) posts open.

Linda Sinclair reposted

Andrew S. MacDonald
@profandrewmac.bsky.social

Very happy to share our new preprint on hallmarks of human #lung #macrophage activation by type 2 cytokines, and metabolic control of this process 🙂. #immunometabolism #ImmunoSky 🧪 @lydiabeckeriii.bsky.social @edinburgh-uni.bsky.social www.biorxiv.org/content/10.1...

biorxiv.orgHallmarks and metabolic regulation of type 2 activated human lung macrophagesAlthough human lung macrophages are heterogenous and play key roles during health and disease, the mechanisms that govern their activation and function are unclear, particularly in type 2 settings. Ou...

Linda Sinclair reposted

Payam Gammage
@mito-oncogene.bsky.social

Okey dokey here goes! First real post - please reshare if appropriate 🙏 🔔We’ve got two postdoc level positions opening in our lab! One wet lab, one computational🔔 We’re a scientifically diverse, friendly bunch working at the interface of mitochondrial biology, metabolism & cancer in Glasgow, UK.

Linda Sinclair
@lindavsinclair.bsky.social

4/n So, we used Ian Ganley's autophagy flux reporter (mCherry-GFP:LC3b) mouse: Flux can be measured by comparing the level of GFP (quenched in autolysosome) to mCherry (stable) fluorescence. *Naïve CD8 Tcells have very autophagy flux, which is REDUCED in response to TCR activation*

Linda Sinclair
@lindavsinclair.bsky.social

14/14 Finally – this work was reviewed beautifully in the accompanying News and Views. www.nature.com/articles/s41... @natimmunol.bsky.social @natureportfolio.nature.com

nature.comAutophagy repression in effector T lymphocytes redefines paradigms in T cell biology - Nature ImmunologyAutophagy, thought to be boosted by T cell receptor or cytokine stimulation, took an unexpected turn in the findings of Sinclair et al. — it is suppressed in activated T cells, facilitating their effe...
Linda Sinclair
@lindavsinclair.bsky.social

11/n Proteomics on naïve CD8 Tcells +/- VPS34 inhibition showed the predominant substrates are mitochondrial proteins. In naïve CD8 T cells mitochondria are constantly pruned to remain healthy. Blocking autophagy results in accumulation of pro-apoptotic proteins eg BAK1 and BIM, and cell death.

Linda Sinclair
@lindavsinclair.bsky.social

9/n “protected proteins” (autophagy targets) include cytolytic effectors; amino acid, glucose and lactate transporters; as well as proteins involved in metabolism (FAO, amino acid metabolism, and glycolysis)

Linda Sinclair
@lindavsinclair.bsky.social

10/n Proteins which are fuelled by autophagy during AA starvation include “protective” proteins eg cell detoxification and survival. *keeping autophagy REPRESSED in effector CD8 cells permits cytolytic and metabolic processes; whilst AA starvation drives autophagy fuelled cell survival proteins*

Linda Sinclair
@lindavsinclair.bsky.social

7/n Does extracellular AA supply/accessibility control autophagy in CD8 Tcells? Yes, autophagy repression in CD8 Tcells was dynamic, and dependent upon extracellular AA availability. In effector CD8 Tcells, this was through VPS34-dependent, but AMPK/mTORC1-independent pathways.

Linda Sinclair
@lindavsinclair.bsky.social

8/n What are the substrates of autophagy in CD8 Tcells? They are different in naïve cells and effector cells! - Proteomics on CTLs showed AA deprivation drives a loss in 55% of proteins ~ ½ of this loss was protected by VPS34 inhibition=autophagy. ½ was not (ie degraded by other mechanisms).

Linda Sinclair
@lindavsinclair.bsky.social

5/n What immune signals are regulating autophagy flux? As well as TCR-activation, Pro-inflammatory cytokines (IL-2, IL-12+IL-18, IL-4, IL-21) repressed autophagy flux; but memory cytokines (IL-15, IL-7) could not.

Linda Sinclair
@lindavsinclair.bsky.social

6/n We saw that autophagy repression correlated with the amino acid (AA) uptake capacity of the cells. ~AA starvation is an evolutionarily conserved autophagy stimulus. ~AA transporter expression is tightly regulated in Tcells: LOW in naïve, HIGH in effector cells and LOW in memory cells.

Linda Sinclair
@lindavsinclair.bsky.social

2/n The basis and framework for this behemoth study was all grown from Tom's PhD work. Tom noted protein and RNA expression of key autophagy machinery/cargo adaptors showed a disconnect during activation and differentiation of CD8 T cells. Protein INCREASED while mRNA DECREASED. What was going on?

Linda Sinclair
@lindavsinclair.bsky.social

3/n Autophagy is a degradation pathway. Is the increased protein expression of autophagy “core components” indicative of REDUCED autophagy flux post activation? (rather than increased in autophagy after immune activation, as currently understood)

Linda Sinclair reposted

Matthew Sinton 🏳️‍🌈
@mcsinton.bsky.social

Delighted to have had the opportunity to write this spotlight with @juanquintana.bsky.social and the lab, on the recent @lydialynch.bsky.social paper, showing rhythmicity of IL-17 expression in adipose! Fascinating paper, which raises loads of cool questions #immunosky www.cell.com/immunity/ful...

cell.comInterleukin-17 and fat: Timing is everythingInterleukin-17 plays a major role in controlling adipose tissue homeostasis. In a recent study published in Nature, Douglas et al. demonstrate that time-of-day-dependent expression of interleukin-17 b...

Linda Sinclair reposted

Varsha Singh
@varshasinghuk.bsky.social

Michael J Fox has had tremendous influence on people with Parkinson's Disease (PD), their carers, families and those working on PD. He is a shining example of what a single person is capable of. Well deserved recognition.

WuTangIsForTheChildren@wutangforchildren.bsky.social

Michael J. Fox receiving the Presidential Medal of Freedom from Joe Biden….why is it so dusty in here now….I’m not crying, you’re crying 🥹🙏

Linda Sinclair reposted

plasmidsaurus
@plasmidsaurus.bsky.social

Organelles meets dinos! 🦖🔬 Featuring Mitosaur, ERsaur, Golgisaur, Lysosaur, and others, it's such a creative take on the cellular world we know and love. 💚 Which dino-organelle is your favorite? Let us know below! 👇

Linda Sinclair reposted

Tcellogic (Sue Kaech)
@tcellogic.bsky.social

T cells get hungry! Check out Shixin Ma's new paper showing nutrient switching controls T cell exhaustion. Nutrients metabolized in the nucleus by ACSS2 and ACLY direct histone acetylation at key loci via binding to specific HATs, indicating a metabolic code guides our histone code. @science.org

Linda Sinclair reposted

Matthew Sinton 🏳️‍🌈
@mcsinton.bsky.social

Just recently I wrote an opinion piece with Shingo Kajimura, based around the idea that adipocytes, besides having energy storage/endocrine function, also act as immune hubs #Immunosky 🧪 1/🧵 febs.onlinelibrary.wiley.com/doi/10.1111/...

febs.onlinelibrary.wiley.comFEBS PressTraditionally, adipocytes have been viewed as energy storage units, which upregulate inflammatory factors in response to obesity. However, emerging evidence demonstrates that adipocytes are highly re...