More on EBV and multiple sclerosis (a topic I’ve written about before). Not only does EBV cause MS, it also appears that MS relapses are linked with EBV reactivation. This may mean that inhibiting reactivation could inhibit relapses.
Synthetic tissue-specific enhancer sequences for mice. I wrote about the Stark lab’s Drosophila enhancer research previously on this blog. But mice are cooler than Drosophila (fight me, fly people!)
Old news in this corner of the Internet, but several antibody vendors (Thermo Fisher is the worst but not the only one) are selling antibodies with faked validation data! I’m just waiting for the day when synthetic binders are good enough to replace antibodies in research.
A variant of twin prime editing1 which drives the integration of large pieces of DNA at targeted sites in the genome. Besides the usual experiments with cancer cell lines, they also tested it with HSPCs and T cells which are more clinically relevant. This appears efficient at the sites they demonstrated in the paper, but it looks like it would take considerable optimization for each new target site. Still pretty cool!
Development of human iPSC-derived brain organoids transplanted into mice genetically engineered to lack most of the cerebral cortex. The genetic knockout strategy was interesting: they made a Cre recombinase “kill switch” that killed any cell expressing Emx1, which is a marker of cortical progentitors:
Design of allosterically controlled enzymes, from David Baker’s lab. The basic idea is that they start with an active enzyme, use RFdiffusion to design an inactive conformation, then design binders that stabilize either the active or the inactive conformation.
Design of new AP-1 family transcription factors by shuffling existing protein domains.
Atlas of somatic mutation rates in normal cells. Relevant for IVG, where minimizing the mutation load of the starting somatic cells is important. From the abstract:
We report the mutation rates and mutational signatures of 53 normal cell types. Most show evidence of linear mutation accumulation over time with single base substitution mutation rates ranging from ∼3.5/year/diploid genome in spermatogonia and sperm, to ∼20/year in postmitotic neurons, ∼50/year in mitotically active colorectal epithelial cells, ∼60/year in kidney proximal tubule cells and hepatocytes, 100s/year in sun-exposed skin epidermal cells and 10-50/year in the remainder.
Comprehensive lineage tracing during mouse embryonic development. This would be really cool to do in a primate embryo. From the abstract:
From one E13.5 embryo bearing ∼7 integrations of a constitutively expressed prime editor and 11 integrations of 6-unit circTAPE, we recover ∼1.75M single-nucleus transcriptomes and reconstruct a time-calibrated phylogeny of 1,340,794 annotated cells.
Similar to my rotation project in David Liu’s lab all the way back in 2019. Since I didn’t end up joining the Liu lab, the project didn’t really go anywhere though.
lineage browser from the last link
https://next-cell.org/app#view=backbone&level=traj&mode=dendro&k=140000&thr=60
"Old news in this corner of the Internet, but several antibody vendors (Thermo Fisher is the worst but not the only one) are selling antibodies with faked validation data! I’m just waiting for the day when synthetic binders are good enough to replace antibodies in research."
So much research is based on WBs that are basically crap. The US govt should sue these companies for effectively defrauding the public for 30 years. As for modern standards- whenever possible, a CRISPR KO and plasmid rescue should be performed to validate ANY antibody as a standard operating procedure, specially for polyclonals from large vendors.