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Zid Lab

@zidlab.bsky.social

UC San Diego Biochemistry studying RNA localization and mitochondria

1,806 Followers  |  222 Following  |  9 Posts  |  Joined: 22.08.2023  |  1.7535

Latest posts by zidlab.bsky.social on Bluesky

Polaroid snapshot of Omar Quintero-Carmonas and me (Ximena)

Polaroid snapshot of Omar Quintero-Carmonas and me (Ximena)

Beautiful green-yellow tree just outside of the Bottomley House at the University of Richmond against a pretty blue sky

Beautiful green-yellow tree just outside of the Bottomley House at the University of Richmond against a pretty blue sky

A red brick building typical of University of Richmond campus

A red brick building typical of University of Richmond campus

My seminar poster has my talk title "Cells Build Robust Organelles from Noisy Processes: Lessons from Algae and Yeast," plus information like the location and date of the talk

My seminar poster has my talk title "Cells Build Robust Organelles from Noisy Processes: Lessons from Algae and Yeast," plus information like the location and date of the talk

Had an amazing time visiting University of Richmond during peak foliage, learned about the innovative teaching and science we'd see more of around the country, and shared my own stochastic biophysics work, old and new. Thank you @omqu.bsky.social for my first ever dept seminar & campus visit

19.11.2025 05:13 β€” πŸ‘ 2    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0
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Metabolic environment-driven remodeling of mitochondrial ribosomes regulates translation and biogenesis Zheng et al. demonstrate that mitochondria remodel the structure and composition of mitochondrial ribosomes in response to metabolic state. This structural β€œgear-switching” mechanism fine-tunes mitoch...

Metabolic environment-driven remodeling of mitochondrial ribosomes regulates translation and biogenesis: Molecular Cell www.cell.com/molecular-ce...

06.11.2025 18:37 β€” πŸ‘ 6    πŸ” 2    πŸ’¬ 0    πŸ“Œ 0
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Secretome translation shaped by lysosomes and lunapark-marked ER junctions - Nature Live-cell imaging of mRNA encoding secretome proteins and translated nascent peptide markers show that secretome translation occurs at endoplasmic reticulum junctions near lysosomes, requires lun...

www.nature.com/articles/s41...
Secretome translation shaped by lysosomes and lunapark-marked ER junctions

05.11.2025 17:03 β€” πŸ‘ 11    πŸ” 5    πŸ’¬ 0    πŸ“Œ 2

Neuronal compartmentalization results in impoverished axonal mitochondria https://www.biorxiv.org/content/10.1101/2025.10.27.684882v1

29.10.2025 19:15 β€” πŸ‘ 5    πŸ” 2    πŸ’¬ 0    πŸ“Œ 1
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Pan-modification profiling facilitates a cross-evolutionary dissection of the thermoregulated ribosomal epitranscriptome Pan-Mod-seq enables systematic, multi-modification mapping of rRNA across life. Applying it to diverse organisms reveals that hyperthermophiles dynamically install stabilizing modifications to support...

Amazing paper from collaborators Schraga Schwartz and Moran Shalev-Benami at Weizmann. Nucleotide resolution sequencing of 16 RNA modifications from diverse organisms cultured under basal and 'extreme' conditions + enzymology, structure, synthesis, and biophysics.

www.cell.com/cell/fulltex...

24.10.2025 17:20 β€” πŸ‘ 11    πŸ” 2    πŸ’¬ 1    πŸ“Œ 1

Our collab w. V Goel, @nicholas-aboreden.bsky.social , J Jusuf, G Blobel, L Mirny, @irate-physicist.bsky.social out in @natsmb.nature.com www.nature.com/articles/s41...

Was co-submitted with @allanaschooley.bsky.social @jobdekker.bsky.social whose paper should also come out soon

Brief thread πŸ‘‡

20.10.2025 18:36 β€” πŸ‘ 55    πŸ” 18    πŸ’¬ 2    πŸ“Œ 2

And it's out!
Our paper on the optimization of smFISH to quantify cytokine mRNAs in T cells is published in EMBO Journal.
Using this protocol, we gathered interesting insights on cytokine mRNAs co-expression and localization in these teeny tiny human cells.
www.embopress.org/doi/full/10....

15.10.2025 21:31 β€” πŸ‘ 29    πŸ” 11    πŸ’¬ 1    πŸ“Œ 0
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From MBoC: Timothy J. Stasevich, Colorado State University, developed All Probes Plasmids (APPs) to simplify single-mRNA translation imagingβ€”just 2 plasmids for multicolor, long-term tracking. www.molbiolcell.org/doi/10.1091/... #CellBiology

13.10.2025 22:24 β€” πŸ‘ 27    πŸ” 9    πŸ’¬ 0    πŸ“Œ 0
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I am thrilled to share our latest story led by the incredibly talented Brooke D’Arcy and Camila Musso. We discover a rich world of local gene expression in radial glia, essential neural and glial precursors, and develop a new method for sub-cellular mRNA manipulation. www.biorxiv.org/content/10.1...

10.10.2025 22:28 β€” πŸ‘ 73    πŸ” 24    πŸ’¬ 4    πŸ“Œ 3
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Online now - the Review "Interconnectivity of mitochondrial protein biogenesis and quality control" from @mitolab.bsky.social et al.

#ProteinImport #Proteaes #Proteolysis #Proteostasis

Read it here: authors.elsevier.com/sd/article/S...

10.10.2025 15:55 β€” πŸ‘ 16    πŸ” 11    πŸ’¬ 0    πŸ“Œ 0
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Mallory is a postdoc in Alexis Komor's lab. She brings gene editing to high schools, showing them what a future in science looks like. Without funding from the NSF, this outreach would not be possible. #BehindEveryBreakthrough

08.10.2025 18:01 β€” πŸ‘ 8    πŸ” 4    πŸ’¬ 1    πŸ“Œ 0
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πŸš€ Our new paper is out @natmethods.nature.com!

Kuffer & Marzilli engineered conditionally stable MS2 & PP7 coat proteins (dMCP & dPCP) that degrade unless bound to RNA, enabling ultra–low-background, single-mRNA imaging in live cells.

πŸ”— www.nature.com/articles/s41...
🧬 www.addgene.org/John_Ngo/

22.09.2025 18:27 β€” πŸ‘ 223    πŸ” 97    πŸ’¬ 6    πŸ“Œ 9
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Wonderful to see our paper on the #organelle signatures of #neurons and #astrocytes out in final form - congratulations, Shannon Rhoads and team!πŸŽ‰ t.co/BPxKlbU6Ou

17.09.2025 17:37 β€” πŸ‘ 99    πŸ” 40    πŸ’¬ 6    πŸ“Œ 1
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Leaflet-specific phospholipid imaging using genetically encoded proximity sensors - Nature Chemical Biology An approach combining bioorthogonal chemistry with genetically encoded fluorogen-activating proteins enables subcellular imaging of phospholipids and glycans, as well as the visualization of lipid tra...

Very excited to share new work out today in @natchembio.nature.com on a new approach - FACES - for selectively imaging of phospholipids and other biomolecules at spatial resolutions down to individual membrane leaflets (1/n) www.nature.com/articles/s41...

15.09.2025 18:03 β€” πŸ‘ 163    πŸ” 70    πŸ’¬ 8    πŸ“Œ 7
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HuD controls widespread RNA stability to drive neuronal activity-dependent responses Neuronal activity shapes brain development and refines synaptic connectivity in part through dynamic changes in gene expression. While activity-regulated transcriptional programs have been extensively...

Our new pre-print from the Greenberg and Churchman labs shows that activity-dependent modulation of RNA stability is a major, and underappreciated, mechanism of gene regulation in neurons. Tutorial below! www.biorxiv.org/content/10.1... (1/11)

09.09.2025 14:41 β€” πŸ‘ 66    πŸ” 22    πŸ’¬ 1    πŸ“Œ 1

Thrilled to announce our #preprint on a new factor in the last line of defense in #translation quality control out on #bioRXiv! Spearheaded by fantastic PhD student @kaushikiyer.bsky.social, supported by ChloΓ© Walter, Alina Kraft, Max MΓΌller and Lena Tittel.

09.09.2025 18:17 β€” πŸ‘ 10    πŸ” 8    πŸ’¬ 1    πŸ“Œ 0

Proximity-specific ribosome profiling using LOV-BirA reveals two distinct strategies for mitochondrially-localized translation: one for long coding sequences and one for short. It was a pleasure to contribute to this beautiful work from Jonathan Weissman @weissmanlab.bsky.social‬ and Jingchuan Luo

27.08.2025 15:29 β€” πŸ‘ 32    πŸ” 7    πŸ’¬ 1    πŸ“Œ 2
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Local Mitochondrial Physiology Defined by mtDNA Quality Guides Purifying Selection The mitochondrial genome (mtDNA) encodes essential subunits of the electron transport chain and ATP synthase. Mutations in these genes impair oxidative phosphorylation, compromise mitochondrial ATP pr...

🚨 Preprint alert! 🚨
My first first-author manuscript is out on bioRxiv!
We developed a new method to monitor mtDNA quality control in yeast, and found that a functional respiratory chain is crucial for the process. @osman-lab.bsky.social
#mtDNA #mitochondria

www.biorxiv.org/content/10.1...

12.08.2025 07:49 β€” πŸ‘ 10    πŸ” 4    πŸ’¬ 1    πŸ“Œ 0
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Side-by-side systematic characterization of novel FPs in budding yeast Fluorescent proteins (FPs) have become indispensable for biological research. Since the discovery of the first FP, Aequorea victoria green fluorescent protein (avGFP), new fluorescent proteins are con...

(Yet another) shout-out to @joachimgoedhart.bsky.social and colleagues for their ongoing technical service to the cell biology community – in this case, the yeast cell biology community. Special kudos for making all the key plasmids available on @addgene.bsky.social. Stellar work all around!

15.08.2025 20:39 β€” πŸ‘ 25    πŸ” 10    πŸ’¬ 1    πŸ“Œ 0
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Organelle-Targeted Laurdans Measure Heterogeneity in Subcellular Membranes and Their Responses to Saturated Lipid Stress Organelles feature characteristic lipid compositions that lead to differences in membrane properties. In cells, membrane ordering and fluidity are commonly measured using the solvatochromic dye Laurdan, whose fluorescence is sensitive to lipid packing. As a general lipophilic dye, Laurdan stains all hydrophobic environments in cells; therefore, it is challenging to characterize membrane properties in specific organelles or assess their responses to pharmacological treatments in intact cells. Here, we describe the synthesis and application of Laurdan-derived probes that read out the membrane packing of individual cellular organelles. The set of organelle-targeted Laurdans (OTL) localizes to the ER, mitochondria, lysosomes, and Golgi compartments with high specificity while retaining the spectral resolution needed to detect biological changes in membrane ordering. We show that ratiometric imaging with OTLs can resolve membrane heterogeneity within organelles as well as changes in lipid packing resulting from inhibition of trafficking or bioenergetic processes. We apply these probes to characterize organelle-specific responses to saturated lipid stress. While the ER and lysosomal membrane fluidity is sensitive to exogenous saturated fatty acids, that of mitochondrial membranes is protected. We then use differences in ER membrane fluidity to sort populations of cells based on their fatty acid diet, highlighting the ability of organelle-localized solvatochromic probes to distinguish between cells based on their metabolic state. These results expand the repertoire of targeted membrane probes and demonstrate their application in interrogating lipid dysregulation.

The 4 chemically targeted Laurdan derivatives (for mitochondria, ER, lyso/endosomes, and the Golgi) that we published last year are now available (at a pretty reasonable price) from Avanti Polar Lipids (cat #880194, 880197, 880193, 880196). These have been very popular! pubs.acs.org/doi/full/10....

15.08.2025 15:57 β€” πŸ‘ 47    πŸ” 14    πŸ’¬ 1    πŸ“Œ 1
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Pew Awards 22 Researchers Biomedical Science Grants

Incredibly honored to be named a 2025 Pew Scholar in the Biomedical Sciences! 🧬 Grateful to Pew Trusts for this recognition and support, and to my awesome lab team, mentors and colleagues at @ucsdhealthsci.bsky.social Excited for what's ahead!
www.pew.org/en/about/new...

12.08.2025 16:59 β€” πŸ‘ 32    πŸ” 2    πŸ’¬ 3    πŸ“Œ 0
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ZBTB11 depletion targets metabolic vulnerabilities in KRAS inhibitor-resistant PDAC - Nature Chemical Biology Depletion of a transcriptional factor ZBTB11 using molecular glue degraders can overcome oxidative-phosphorylation-mediated KRAS inhibitor resistance in pancreatic ductal adenocarcinoma with low acute...

Excited to share our latest work developing molecular glue degraders of ZBTB11, now out in @natchembio.nature.com
www.nature.com/articles/s41...

11.08.2025 13:51 β€” πŸ‘ 51    πŸ” 16    πŸ’¬ 2    πŸ“Œ 0
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Protein language models reveal evolutionary constraints on synonymous codon choice Evolution has shaped the genetic code, with subtle pressures leading to preferences for some synonymous codons over others. Codons are translated at different speeds by the ribosome, imposing constrai...

This preprint from Helen Sakharova is one of the coolest things to come out of my lab: β€œProtein language models reveal evolutionary constraints on synonymous codon choice.” Codon choice is a big puzzle in how information is encoded in genomes, and we have a new angle. www.biorxiv.org/content/10.1...

07.08.2025 08:29 β€” πŸ‘ 215    πŸ” 83    πŸ’¬ 6    πŸ“Œ 4
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RNA triggers chronic stress during neuronal aging Neurodegenerative diseases are linked with dysregulation of the integrated stress response (ISR), which coordinates cellular homeostasis during and after stress events. Cellular stress can arise from ...

This is quite relevant - RNA triggers chronic stress during neuronal aging
Thanks @frezzalab.bsky.social for the hint!!!

www.biorxiv.org/content/10.1...

06.08.2025 09:18 β€” πŸ‘ 4    πŸ” 2    πŸ’¬ 0    πŸ“Œ 0
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Biochemical analysis of human eIF4E-DCP2 interaction: Implications for the relationship between translation initiation and decapping All eukaryotic mRNAs bear a 7-methylguanosine cap on their 5’ end. The 5’ cap enables mRNA translation by binding directly to eIF4E; which further recruits other factors and the 40S ribosome. Addition...

I nice little story from the lab: dx.plos.org/10.1371/jour...

04.08.2025 14:48 β€” πŸ‘ 12    πŸ” 5    πŸ’¬ 0    πŸ“Œ 0
Picture of a smiling person holding up a copy of a book.

Picture of a smiling person holding up a copy of a book.

First copies of my book are here!! As a new faculty member, I realized that in addition to my research job, I also had a leadership job…and I wasn’t prepared for that.

This book is the guide I wish I’d had then, with the goal of helping others now.
Β 
jenheemstra.com/book

26.07.2025 17:35 β€” πŸ‘ 311    πŸ” 66    πŸ’¬ 12    πŸ“Œ 4
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Beyond excited to share our #NewPaper in @cellcellpress.bsky.social! Inflamed environments acidify intracellular #pH. BRD4 senses this via transcriptional condensates, tuning #macrophage responses to match demand and consequences of #inflammation authors.elsevier.com/sd/article/S...

22.07.2025 13:24 β€” πŸ‘ 79    πŸ” 29    πŸ’¬ 6    πŸ“Œ 2
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Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions Author summary Mitochondria are essential cellular organelles that perform many important roles in regulating metabolism. They are dynamic in form, function and composition which is crucial to maintai...

Delighted to share our latest work looking at the role of the RNA-binding proteins Clu1 (yeast)/Clu (flies) in regulating the translation of #mitochondria proteins. Really interesting regulator of mito biology.

Huge, long-running effort by PDRA Leonor Miller-Fleming πŸ‘
dx.plos.org/10.1371/jour...

16.07.2025 11:35 β€” πŸ‘ 21    πŸ” 9    πŸ’¬ 1    πŸ“Œ 0
mRNA 3β€²UTRs chaperone intrinsically disordered regions to control protein activity More than 2,700 human mRNA 3β€²UTRs have hundreds of highly conserved (HC) nucleotides, but their biological roles are unclear. Here, we show that mRNAs with HC 3β€²UTRs mostly encode proteins with long intrinsically disordered regions (IDRs), including MYC, UTX, and JMJD3. These proteins are only fully active when translated from mRNA templates that include their 3β€²UTRs, raising the possibility of functional interactions between 3β€²UTRs and IDRs. Rather than affecting protein abundance or localization, we find that HC 3β€²UTRs control transcriptional or histone demethylase activity through co-translationally determined protein oligomerization states that are kinetically stable. 3β€²UTR-dependent changes in protein folding require mRNA-IDR interactions, suggesting that mRNAs act as IDR chaperones. These mRNAs are multivalent, a biophysical RNA feature that enables their translation in network-like condensates, which provide favorable folding environments for proteins with long IDRs. These data indicate that the coding sequence is insufficient for the biogenesis of biologically active conformations of IDR-containing proteins and that RNA can catalyze protein folding. ### Competing Interest Statement The authors have declared no competing interest. Pershing Square Foundation, https://ror.org/04tce9s05 G. Harold & Leila Y. Mathers Foundation National Institutes of Health, DP1GM123454, R35GM144046 Memorial Sloan Kettering Cancer Center, https://ror.org/02yrq0923, P30 CA008748

New paper:
More than 2700 human 3β€²UTRs are highly conserved. These 3β€²UTRs are essential components in mRNA templates, as their deletion decreases protein activity without changing protein abundance. Highly conserved 3β€²UTRs help the folding of proteins with long IDRs.

www.biorxiv.org/content/10.1...

07.07.2025 14:28 β€” πŸ‘ 158    πŸ” 66    πŸ’¬ 4    πŸ“Œ 5
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Drug Repurposing Screen Identifies an HRI Activating Compound that Promotes Adaptive Mitochondrial Remodeling in MFN2-deficient Cells Pathogenic variants in the mitochondrial outer membrane GTPase MFN2 cause the peripheral neuropathy Charcot-Marie-Tooth Type 2A (CMT2A). These mutations disrupt MFN2-dependent regulation of diverse as...

New work from the lab (w/ @preronabora.bsky.social @mashiatzaman.bsky.social @mitomorph.bsky.social @nanigrotjahn.bsky.social) identifying a compound that activates OMA1-DELE1-HRI signaling to induce mitochondrial remodeling in MFN2-deficient cells. Check it out πŸ‘‡
www.biorxiv.org/content/10.1...

27.06.2025 15:52 β€” πŸ‘ 25    πŸ” 6    πŸ’¬ 0    πŸ“Œ 1

@zidlab is following 20 prominent accounts