David Breslow Lab

Lots of potential for future ciliary (and non-ciliary) screening applications. Great work by all authors, especially postdoc Jingbo Sun. And great collaboration with the Khokha lab!

We find that SMIM27/TZMP1 KO cells fail to form cilia. TZMP1 localizes to the transition and by IP/MS is part of the MKS complex at the transition zone. With Mustafa Khokha, we find conserved roles in ciliary function in Xenopus embryos.

Among hits, we characterize SMIM27/TZMP1 as a new microprotein component of the ciliary transition zone. A crazy gene... prev thought to be a lncRNA, it encodes a 55aa protein and overlaps another gene such that its start codon overlaps the start codon of a gene expressed from opposite strand!

We applied this technology in a series of genome-wide and targeted screens... We find known and novel ciliary regulators and we combine results from complementary screens to get multi-parameter phenotypic profiles with rich functional information.

Two methodologic highlights: 1) photoactivation in fixed cells using a PA small molecule dye, enabling use of Ab staining to define phenotypes (flexible analysis of diverse markers, including PTMs), 2) use of commercial microscope hardware and software (don't need to be an optics/programming expert)

Here we build on prior strategies that convert microscopy phenotypes into FACS-sortable fluorescence differences. The workflow combines: automated high-throughput imaging; AI-based ID of cells with desired phenotype; targeted photoactivation of these cells; cell recovery by FACS for sgRNA sequencing

A microscopy-based CRISPR screening platform enables organellar functional genomics and illuminates ciliary biology Sun et al. develop a microscopy-based CRISPR screening platform that combines ease of implementation with flexible analysis of live-cell or antibody-based markers. Screens in human cells using a serie...

Ever wanted to do a genome-scale CRISPR screen for a microscopy phenotype? Pooled CRISPR screens are amazing, but hard to combine with imaging... Excited to share our latest work in Dev Cell on a technology platform for imaging screens and applications to primary cilia: www.cell.com/developmenta...

An enzymatic cascade enables sensitive and specific proximity labeling proteomics in challenging biological systems - Nature Communications Proximity labeling allows proteomic mapping of subcellular structures. Here, Sroka et al. develop in situ APEX activation (iAPEX) to overcome limitations of labeling specificity and H2O2 toxicity, app...

Thrilled to share "in situ APEX activation" (iAPEX), a proximity labeling technology for subcellular #proteomics applied to primary #cilia. iAPEX uses an enzymatic cascade, in which a D-amino acid oxidase locally produces H2O2 to activate ascorbate peroxidase.
www.nature.com/articles/s41...

A versatile cohesion manipulation system probes female reproductive age-related egg aneuploidy - Nature Aging To study pathways that lead to aneuploidy during aging, the authors provide a system that enables cohesion protein depletion in mouse oocytes, mimicking effects that occur during aging. They uncover a...

We built a targeted protein degradation–based system to mimic reproductive age-related aneuploidy in young eggs - revealing how chromosome errors associated with female infertility arise with age. 🧬✨
With @jiyeonleem.bsky.social and our team at Yale MCDB.

Read: www.nature.com/articles/s43...

Great work by all authors, especially first Breslow lab grad student Shane Elliott. And thanks also to excellent collaborations at Yale with labs of Angelique Bordey and Tony Koleske

3) it is noteworthy that a GOF CRISPRa screen was able to uncover a connection to a disorder caused by somatic activating mutations; possibly CRISPRa screening may be broadly useful for studying such diseases caused by somatic mutations ...

Potential implications: 1) aberrant cilia disassembly may be a recurrent feature of FCD that could contribute to pathogenesis, 2) excess cilia disassembly may be pathologic and could be considered a non-canonical basis for ciliopathy (typically caused by impaired formation of cilia), ...

As FCD is often caused by somatic GOF mutations, we wondered if aberrant cilia disassembly may occur in FCD. We found that FCD-linked mutations in SARM1 or RhoA act like GOF variants and potentiate cilia loss. Cilia loss via SARM1 also occurs for mTORC1-activating alterations commonly seen in FCD...

From hits, we defined a cilia disassembly pathway formed by GPCRs (F2R, LPAR1), SARM1 NADase, centrosomal Ca signaling, and RhoA.This pathway is necessary and sufficient for cilia disassembly.
Serendipitously, we noticed overlap between pathway components and genes mutated in an FCD cohort...

A CRISPR activation screen reveals a cilia disassembly pathway mutated in focal cortical dysplasia A gain-of-function screen uncovers a cilia disassembly pathway linked to genes somatically mutated in neurodevelopmental disease.

Excited to share our latest work on a new cilia disassembly pathway and a link between this pathway and the neurological disorder focal cortical dysplasia: www.science.org/doi/10.1126/...
Brief summary: we used a genome-wide CRISPRa GOF screen to identify negative regulators of ciliary signaling...

Nuclear receptor-neurotransmitter coupling links behavior to metabolic state Animals must flexibly respond to environmental stimuli to survive, and optimal responses critically depend on the organism's current needs. Many organisms have evolved both cell-intrinsic and intertis...

I'm thrilled to share our new preprint, in which we've found that neurotransmitters can be chemically "marked" as a way to incorporate metabolic history - such as diet or life stage. www.biorxiv.org/content/10.1... Led by Porhathai "Un" Malaiwong, Allen Schroeder and Tia Brown. (1/6) 🧵

It seems there are many type 4 R01s issuing mult years of funding at once, possibly in lieu of standard non-competing renewals (i.e. MYF). I see ~220 awards, >450 grant-years, >$175m direct costs. I'm not familiar with type 4, but looks like ~10X as many since May than all of last year.

Calling all biologists! 📢

Is your research at the cutting edge of synthetic biology, genomics or AI?

Apply to join our team of world-class scholars!🔬🦠

Tenure-track Assistant Professor
Anticipated Start Date: July 1, 2026

#hiring #genomics #biology
apply.interfolio.com/172428

Establishing a Fixed Time Period of Admission and an Extension of Stay Procedure for Nonimmigrant Academic Students, Exchange Visitors, and Representatives of Foreign Information Media Unlike most nonimmigrant classifications, which are admitted for a fixed time period, aliens in the F (academic student), J (exchange visitor), and most I (representatives of foreign information media...

Very few PhD students finish within 4 years. But international students will need to do that if US proposed visa rules change go through.

Sound reasonable to you?

Fed register is accepting comments for next month. Details at the link & comment button

www.federalregister.gov/documents/20...

“The Senate Committee on Appropriations is scheduled to release its proposal for NIH’s 2026 budget later this week…The committee could include language that would prohibit the multiyear funding plan or extend the timeline for the transition.”🧪

Want to publish a NIH-funded paper in Nature? Well - unless your institution has an agreement with Springer, you'll have to be mega-rich to be compliant with NIH's new no-embargo policy. Springer is insisting on gold OA - that's $12,690 and that's extortion.

That is very helpful! Colleague here was just persuaded to pay a >$10k APC for a Cell Press journal - nice to know this may be unnecessary

Nice that JCB / RUP has clear guidance with their ‘Green’ option. Any idea if Cell Press or Nature journals allow this?

the word alert is in a purple circle ALT: the word alert is in a purple circle

ACTION ITEM-----ACTION ITEM

Implementation of Schedule F

This is what a lot of us have been worried about.

This allows for many civil service positions to replaced with political appointees. This could include NIH institute directors and even POs.

BUT THERE IS A COMMENT PERIOD...

1/n

We're live! @inikon.bsky.social used modular proximity labeling to identify ciliary EV cargo in #celegans. This EV-TurboID approach can be applied in cell- & tissue-specific manners to define the composition of distinct EV subtypes, a major challenge of the EV field.

www.nature.com/articles/s41...

Trump promised scientific breakthroughs. Researchers say he’s breaking science. NIH funding for biomedical research has abruptly fallen by billions of dollars, with many grant decisions on hold. Trump officials say they’re reviewing the agency.

Powerful new Washington Post story up...

wapo.st/426d9fT

(Gift link)

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Application at NINDS now shows Apr 10 council date in eRA Commons. NIGMS application shows May 22, which is the date that was planned by GM for the following cycle. Both apps were originally supposed to have Council in Feb...

Trypanosome doublet microtubule structures reveal flagellum assembly and motility mechanisms The flagellum of Trypanosoma brucei drives the parasite’s characteristic screw-like motion and is essential for its replication, transmission, and pathogenesis. However, the molecular details of this ...

Trypanosome doublet microtubule structures reveal flagellum assembly and motility mechanisms | Science www.science.org/doi/10.1126/...

Congrats to Anna Seminara on her paper out today in @cp-cellchembiol.bsky.social reporting a new approach to metabolite depletion using a bacterial ABC transporter, applied to study the antioxidant ergothioneine in H. pylori!

Stand up for science event on March 4th at 5:30pm at East Rock Brewery!

CT folks! Let’s come together and make signs for #standupforscience! @luskinglab.bsky.social