1/A picture is worth a thousand words but what if they can say more?! We developed live-cell FLIM approaches to track protein interactions within RNA-protein condensates – Our first paper is now out in @JCellBiol! https://t.co/UF6T43xwqv
Excited to share our new paper: 'LASER couples damage sensing to ESCRT assembly for lysosome repair.' Congrats to dream team @clairegoul and @aakritijain24 for uncovering a new lysosome repair pathway and its connection to neurodegeneration. https://t.co/ZdGtlU0wke
Wu and Hegde annotate & analyze the topology of 4,863 human endoplasmic reticulum–inserted membrane proteins & their 20,546 transmembrane domains, showing transmembrane domains inserted by different pathways can tolerate different biophysical properties https://t.co/PUO8qu4UWu
5.5 years and two babies later, my postdoctoral work is finally out in Cell today! So very grateful to everyone who made this possible.
Nuclear envelope budding enables export of large transcripts in muscle... https://t.co/cIDGyUvNlA
We have developed a cysteine-free, highly thermostable tagging system, UTag, that enables single-mRNA translation tracking in live cells. You may wonder how different tagging systems affect translation kinetics—we addressed this by performing a systematic comparison.
First post, big news: thrilled to announce our first lab paper is out in Science Advances! We show that AMPK activation can suppress liver cancer development. Grateful to our team and excited for what’s next.
https://t.co/8HzNFi1BGL
1/ Thrilled to share our new paper in @Nature: “CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly.” From our lab together with @apsarruda, led by co–first authors @alymathiowetz and @EmilyMeymand. 🥳
https://t.co/LHO31rNaxi
New work describes our efforts to achieve CRISPR editing of the mitochondrial genome.
https://t.co/8Jc51WnEmg
The CRISPR toolbox has revolutionized the study of nuclear DNA, but the mitochondrial genome (mtDNA) has remained out of reach, mainly because there are no known ways to deliver sgRNAs across both outer and inner mitochondrial membranes.
Yet many organisms have evolved mechanisms to transport RNAs across their mitochondrial membranes. Trypanosomes, for example, do not encode any tRNAs in their mtDNA, and must import all of them from the cytosol to support intra-mitochondrial protein translation.
We started with yeast. We engineered a strain that must repair a STOP codon in mtDNA (an arginine biosynthesis gene) to survive. After screening a library of sgRNA import sequences, we identified one that enables a small degree of functional CRISPR editing in mitochondria.
Graduate student Sifei Yin obtained these exciting results several years ago, and spent the intervening time understanding how sgRNA import works, and how to make it better. Read the paper to learn what she uncovered!
1/ New preprint out! We show that PROTAC-induced ubiquitination can bypass canonical ERAD to degrade ER membrane proteins. Wonderful collaboration w/ @DanNomura and huge credit to grad student superstar Sydney Tomlinson!
https://t.co/CT5knDfjSM
In Memoriam: Bert W. O'Malley, M.D.
It is with great sadness that we announce the death of Dr. Bert W. O'Malley, Baylor College of Medicine chancellor, and former chair of the Department of Molecular and Cellular Biology. He also served as the associate director of basic research in the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine.
Considered the ‘founding father’ in the field of molecular endocrinology, Dr. Bert O’Malley was born in Pittsburgh, Pa. and received his Bachelor of Science degree from the University of Pittsburgh and his medical degree from the University of Pittsburgh School of Medicine. He did his clinical internship and residency training at Duke University Medical Center and spent four years at the National Institutes of Health, where he was head of the Molecular Biology Section of the Endocrine Branch of the National Cancer Institute of the National Institutes of Health.
He then served as the Lucious Birch Professor and Director of the Reproductive Biology Center at Vanderbilt University before joining Baylor College of Medicine as chair of the Department of Molecular and Cellular Biology in 1973, a position he held for 45 years.
During his time in this role, the department was routinely listed in the top five in the nation in securing National Institutes of Health funding; more than five times as No. 1. He published more than 700 papers and holds 29 patents in the fields of gene regulation, molecular endocrinology, steroid receptor and coactive action and cell proteomics and metabolism.
In July 2018, O’Malley was named the fourth chancellor of Baylor College of Medicine and stepped down as chair of the department to assume the role of chancellor, but continued to direct his research lab. As chancellor, he advised the president of Baylor College of Medicine, participated in strategic planning activities and acted as an ambassador for the College. He was a member of the NCI-designated Dan L Duncan Comprehensive Cancer Center at Baylor.
O’Malley changed the understanding of endocrinology in a fundamental way. He focused his research on the molecular mechanisms that guide gene regulation in endocrinology and endocrine cancers, including how hormones, receptors and coactivators contribute to the disease process. His pioneering work in this field has shown that intracellular hormones and cofactors act at the level of DNA to regulate the production of proteins and affect the function of the cell.
Research Highlights:
Dr. Bert W. O'Malley received the 2013 Endocrine Regulation Prize of the Foundation IPSEN at the 15th European Congress of Endocrinology on April 29, 2013..
O’Malley’s lab discovered and was the first to solve the structure of a functional receptor-coactivator complex on DNA capable of regulating gene transcription in vitro. In addition, he showed that steroid receptor coactivator-2 (SRC-2), which is highly elevated in a variety of tumors, is likely implicated in metabolic coordination of cancer metastasis, opening the possibility of therapeutically targeting the SRC-2 pathway.
His work with steroid receptor coactivator-3 (SRC-3), a prognostic marker for aggressive human breast cancer, showed that small-molecule inhibitors that directly bind SRC-3 cause selective degradation of the complex, hereby killing cancer cells with no observable toxicity. Small-molecule inhibitors represent a new type of oncologic drugs that target coactivators.
In addition, Dr. O’Malley’s work showed in a mouse model of heart disease, that stimulating SRC-3 with small-molecule MCB-613 initiated a complex cascade of events in tissue repair and modulation of the inflammatory response that reduced fibrosis, attenuating loss of cardiac function after myocardial infarction. These findings open the possibility of novel therapies to regulate the progression of heart failure via SRC-3.
His work also revealed a role for SRC-3 in regulatory immune T cells (Tregs) that promote cancer growth by inhibiting anti-cancer immune responses. He also showed that SRC-3 is significantly enriched in both murine and human Tregs. Inhibiting SRC-3 in Tregs in the lab stopped them from reducing the anti-tumor response, suggesting that modulating SRC-3 in Tregs might help control cancer growth.
Dr. O’Malley will be missed greatly and his contributions to cancer research will live on for decades to come.
@Gandhar_Datar joined the lab when the world was shutting down, having just gotten started with guidance from @therealDrGundry and @BrunettiLab, who then moved on in their careers. Tough work in isolation until @RibackLab joined @bcmhouston, when informal chats got us thinking about the project in a whole new way. We considered how the aberrant function of NPM1c was related (or not) to its nucleolar WT function. A great collaboration grew, with Gandhar deeply learning both hematology and biophysics! Many ppl world-wide contributed and @sciencyelmira was the closer, getting the in vivo models working. Thanks to all, including the reviewers and editors for feedback.
1/ Excited to share our new study with @Brumbaugh_JB, now out in @NatureBiotech! P-bodies selectively sequester RNAs encoding cell fate regulators, often from the preceding developmental stage. Releasing these RNAs can drive changes in cell identity. 🧵https://t.co/D7fnkJgNQ6
Today’s NCB. The cytoplasmic intrinsically disordered regions (IDRs) of ER-phagy and mitophagy receptors are interchangeable, required and sufficient for the ER and mitochondria fragmentation required for lysosomal clearance of the organelle’s portions.
https://t.co/MK6dTmBNgD
Two is better than one for organelles! Our latest work in Advanced Optical Materials shows how a fluorophore can target simultaneously lipid droplets and the endoplasmic reticulum, measuring micro-polarity during homeostasis and ferroptosis
https://t.co/NgAhRkXAx9
@AdvSciNews
How does the cBAF complex use disordered protein to engage diverse transcriptional regulators like YAP1, SOX2, and CBP/p300? San’s tweetorial and new Mol Cell paper reveal β-catenin’s role as a molecular adapter