2025 was a year full of great scientific discoveries and breakthroughs. Here, I want to highlight 10 papers that got me really excited. Of course, this is a highly subjective selection and I am sure I am forgetting some papers that I would love to include, but here it goes: (1/12)

Tags, reporters, luciferase — oh my! To celebrate the expansion of the Promega Plasmid Collection, we’re spotlighting some of our most popular blogs on the technologies researchers rely on every day — tools you can access through Addgene.

I wrote down some of my thoughts down on the current race to build virtual cell models. Overall, excited and wary about the work ahead. Also, it's my first post to Substack; getting more excited about it as a replacement for X and Blue Sky. srikosuri.substack.com/p/the-elusiv...

The elusive virtual cell

Rosetta Stone or Moby Dick?

srikosuri.substack.com

Lux Capital & @wolfejosh.bsky.social are launching the Lux Science Helpline - a $100M commitment to support American scientists whose research is threatened by funding cuts, bureaucratic hurdles, and career roadblocks - that expands our Lux Labs program. www.luxcapital.com/news/our-hel...

An update: After the diagnosis change to AML/myeloid sarcoma, we got a lot of great input. We’ve decided to go to St Jude’s to enroll in a clinical trial. We left for Memphis yesterday. We’ll be staying here for the next several months. Anxious but ready for the path ahead.

Quick update: Thanks so much for the outpouring of support and help. We learned a lot in the last week and the tumor is actually a myeloid sarcoma likely derived from early AML, with the hope of possible targeted therapies as well (KMT2Ar).

Sri Kosuri@srikosuri.bsky.social · last yr.

It’s been a tough few weeks. My 10yo daughter was diagnosed with a very rare, aggressive cancer called interdigitating dendritic cell sarcoma (IDCS). I’m reaching out to identify clinicians/patients who have encountered pediatric IDCS or other (non-LCH) dendritic or histiocytic sarcomas cases.

It’s been a tough few weeks. My 10yo daughter was diagnosed with a very rare, aggressive cancer called interdigitating dendritic cell sarcoma (IDCS). I’m reaching out to identify clinicians/patients who have encountered pediatric IDCS or other (non-LCH) dendritic or histiocytic sarcomas cases.

Serenity now

a man in a kitchen with a sweater on that says oh no i am fine serenity now .

ALT: a man in a kitchen with a sweater on that says oh no i am fine serenity now .

media.tenor.com

This is part of my effort of rewriting all materials for my UT Austin dataviz class in Quarto. It's going very well. Most importantly, I now have live exercises integrated into the site, thanks to Quarto live. Check it out here: wilkelab.org/SDS366/

Claus Wilke@clauswilke.com · 2y ago

Some years ago I wrote a simple R app to explore colors in HCL space. While it's clunky, it still is my preferred way of selecting colors, because it offers features other color selectors don't normally have. Today, thanks to shinylive, the app is available standalone. 🧵

Check out our work, where we discover how receptor GPCR senses pH! We solved a longstanding question by developing foundational GPCR DMS tech dev + structural bio! Led by brilliant PhD student @matthewkhoward.bsky.social and Nick Hoppe w/ @amanglik.bsky.social! www.cell.com/cell/fulltex...

Molecular basis of proton sensing by G protein-coupled receptors

Howard et al. combine mechanistic deep mutational scanning, cryo-EM, and constant-pH molecular dynamics simulations to provide a holistic view of proton activation in human pH-sensitive GPCRs.

cell.com

Matt Howard@matthewkhoward.bsky.social · 2y ago

Happy New Year! (and first post here 😀) Excited to share the final version of our work where we combine deep mutational scanning, cryo-EM, and molecular dynamics to further resolve the mechanisms of pH sensing in GPCRs. 🧵(1/n) www.cell.com/cell/fulltex...

Today's holiday ☕ reading is this 2024 paper on PARIS, a bacterial defense system shaped like a literal propeller that responds to viral infection by hitting the cellular self-destruct button - cleaving an essential tRNA. www.nature.com/articles/s41...

A virally encoded tRNA neutralizes the PARIS antiviral defence system - Nature

Structural and functional studies reveal how viral proteins trigger the phage antirestriction induced system (PARIS) to degrade host tRNA and how viral tRNAs suppress the PARIS nuclease and thereby ov...

nature.com

Really beautiful paper by @kjarmache.bsky.social revealing read-write mechanisms of histone ubiquitylation by Polycomb complexes - through an intricate interplay of ubiquitin binding and ubiquitin transfer. Congratulations to all authors! www.nature.com/articles/s41...

Read–write mechanisms of H2A ubiquitination by Polycomb repressive complex 1 - Nature

Cryo-electron microscopy and biochemical studies elucidate the read–write mechanisms of non-canonical PRC1-containing RYBP in histone H2A lysine 119 monoubiquitination and their roles in maintaining e...

nature.com

Out now - National Academies consensus report on Understanding and Addressing Misinformation About Science 🧪 It was a privilege to serve as one of the 15 committee members from a wide range of scientific disciplines who put this report together. Quick 🧵1/ www.nationalacademies.org/our-work/und...

In new study, we measure how all mutations to rabies G affect cell entry & antibody neutralization Sheds light on constraints on type III fusion proteins, suggests ways to stabilize G vaccine antigens, and quantifies antibody robustness to rabies variation www.biorxiv.org/content/10.1...

Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations

Rabies virus causes nearly 60,000 human deaths annually. Antibodies that target the rabies glycoprotein (G) are being developed as post-exposure prophylactics, but mutations in G can render such antib...

biorxiv.org

What do GWAS and rare variant burden tests discover, and why? Do these studies find the most IMPORTANT genes? If not, how DO they rank genes? Here we present a surprising result: these studies actually test for SPECIFICITY! A 🧵on what this means... (🧪🧬) www.biorxiv.org/content/10.1...

Specificity, length, and luck: How genes are prioritized by rare and common variant association studies

Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes. Although these methods are conceptually similar, we show by anal...

biorxiv.org

The responses to this are why change is not really going to happen within the universities themselves. I’m excited that AI has the possibility to break the cost curves to broad access to education. Lots of work to do, and thanks to those putting in that work to build a brighter future.

Joshua Gans@joshgans.bsky.social · 2y ago

So excited to tell you about my new venture with @afinetheorem.bsky.social called All Day TA (@alldayta.bsky.social) open.substack.com/pub/joshuaga...

I'm thrilled to announce a new preprint describing collaborative work with Ajay Jain and Ann Cleves Jain, "Deep-Learning Based Docking Methods: Fair Comparisons to Conventional Docking Workflows". arxiv.org/abs/2412.02889

Deep-Learning Based Docking Methods: Fair Comparisons to Conventional Docking Workflows

The diffusion learning method, DiffDock, for docking small-molecule ligands into protein binding sites was recently introduced. Results included comparisons to more conventional docking approaches, wi...

arxiv.org

"Wuhan lab samples hold no close relatives to virus behind COVID" That should settle it, right? The problem, of course, it won't because we're dealing with conspiracy theories and not scientific inquiry - no amount of additional data will change un-evidenced beliefs. www.nature.com/articles/d41...

Wuhan lab samples hold no close relatives to virus behind COVID

Shi Zhengli, the virologist at centre of COVID lab-leak theory, reveals coronavirus sequences from Wuhan institute.

nature.com

Is there a way to do starter pack for people to block? Would love to just block folks en masse that are cheering on the execution of a company CEO b/c they hate capitalism or whatever. It's insufferable.

James Catterson@scotsfriction.bsky.social · 2y ago

Agreed. I've seen some quite shocking posts from US colleagues about it actually. And these are prestigious scientists I'm talking about too. 😔

Could one envision a synthetic receptor technology that is fully programmable, able to detect diverse extracellular antigens – both soluble and cell-attached – and convert that recognition into a wide range of intracellular responses, from gene expression and real-time fluorescence to modulation..

Have been thinking about Brian Thompson and his family all day. This one hits home. You kiss your kids goodbye and get on a plane, eat dinner with colleagues prepare your presentation and walk toward the conference hotel. A scenario we all have lived dozens of times. The family must be devastated 😞

First post on bsky to highlight our latest work on smell receptors (www.nature.com/articles/s41...). Odorant receptors are notoriously challenging to work with - we used a classic strategy from protein engineering to get a peek into how these receptors recognize such a diversity of smells.

go.bsky.app/QTL6EqT

The final report from the COVID Sub Committee is released and it is as expected given that the origin "has been contorted by politics, while scientific discourse has been abandoned in pursuit of a preferred, coordinated narrative", as I stated in my written testimony. BUT, there's a bombshell.. 🧵👇

Three BioML starter packs now! Pack 1: go.bsky.app/2VWBcCd Pack 2: go.bsky.app/Bw84Hmc Pack 3: go.bsky.app/NAKYUok DM if you want to be included (or nominate people who should be!)

New blogpost: The ABCs of Alphafold 3, Boltz and Chai-1 blog.booleanbiotech.com/alphafold3-b...

💡💥Here’s a modest proposal I’ve been pondering for a while on how to change the PEER REVIEW process and start more community-driven SCIENCE FUNDING. Lots of feedback/discussion welcomed! Other variants of the idea might exist already—not claiming originality. (a long 🧵) (1/9)

Anyone’s dm’s still broken? I keep on getting an error called “bad token method”. DMs haven’t worked from the start for me. I’ve tried reinstalling the app and logging off and then back in. Anyone have any fixes?

Heterozygous mutations in leptin receptor gene (LEPR) do not cause obesity. The finding goes against the rationale for a recent clinical trial that test setmelanotide for obesity treatment in heterozygous carriers of LEPR variants. Delplanque et al. AJHG www.sciencedirect.com/science/arti...