Is single-molecule protein sequencing here yet? Nature Methods

As instruments and approaches emerge for single-molecule protein analysis, some developers and early users share their first impressions with Nature Methods. 🧪

Protein codes promote selective subcellular compartmentalization Cells have evolved mechanisms to distribute ~10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must assemble. Here, we demonstrate that prote...

Cool paper using LLM to discover a protein sequence code for subcellular localization 👏

www.science.org/doi/10.1126/...

Timescales in Cell Biology

Single-molecule states link transcription factor binding to gene expression - Nature A study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription factor bind...

Beautiful single-molecule footprinting study from the Greenleaf and Bintu labs www.nature.com/articles/s41...

Coordinated inheritance of extrachromosomal DNAs in cancer cells - Nature Cooperative species of extrachromosomal DNAs are coordinately inherited through mitotic co-segregation.

Cancer cells often harbor oncogenes outside chromosomes on extrachromosomal DNA (ecDNA), which is unevenly inherited by dividing cells. We reported in Nature last week that collectives of ecDNAs are inherited together by dividing cancer cells. 1/
www.nature.com/articles/s41...

Too often we spend only two weeks choosing a problem and then many years trying solving it, but this limits our potential impact.
A must read for PhD students: Problem choice and decision trees in science and engineering.
pubmed.ncbi.nlm.nih.gov/38608651/

Decoding the epigenetics and chromatin loop dynamics of androgen receptor-mediated transcription - Nature Communications Androgen receptor (AR) is the critical driver of nearly all prostate cancer. The authors show that AR activation causes specific pre-existing chromatin loops to increase contact frequency with target ...

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

There's a lot that I'm proud of in this paper, but my favorite experiment is knocking out Raf1 and rescuing the phenotype with mitochondrial-localized Raf1 or plasma-membrane localized Raf1 and being able to separate Raf1's typical signaling function from our novel mitochondrial function.

Almost 20 years ago, Galmiche and Fueller published a review describing the role of outer-mitochondrial Raf1 in regulating apoptosis and they speculate that Raf1 may also exist inside of the mitochondria to regulate metabolism. They were right!

Mitochondrial Raf1 Regulates Glutamine Catabolism Raf1 is present within the mitochondrial matrix, where it binds GLS to regulate glutamine catabolism and tumorigenesis. In cancer, Raf1 activation occurs via mechanisms that include mutation of upstr...

Republicizing my preprint from earlier this year! We found that mitochondrial Raf1 upregulates glutamine catabolism in cancer cells.

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