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Institution

Howard Hughes Medical Institute

NonprofitChevy Chase, Maryland, United States
About: Howard Hughes Medical Institute is a nonprofit organization based out in Chevy Chase, Maryland, United States. It is known for research contribution in the topics: Gene & RNA. The organization has 20371 authors who have published 34677 publications receiving 5247143 citations. The organization is also known as: HHMI & hhmi.org.


Papers
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Journal ArticleDOI
19 Jan 2012-Nature
TL;DR: It is shown that human cells use reductive metabolism of α-ketoglutarate to synthesize AcCoA for lipid synthesis and support lipid synthesis in mammalian cells.
Abstract: Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty-acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and ATP citrate lyase in the cytosol. However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near-stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle and fatty-acid synthesis. Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis, the regulation and use of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells use reductive metabolism of α-ketoglutarate to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived α-ketoglutarate for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau tumour suppressor protein preferentially use reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon use to produce AcCoA and support lipid synthesis in mammalian cells.

1,482 citations

Journal ArticleDOI
16 Apr 2010-Cell
TL;DR: It is shown that DNA breaks in Brca1-deficient cells are aberrantly joined into complex chromosome rearrangements by a process dependent on the nonhomologous end-joining (NHEJ) factors 53BP1 and DNA ligase 4, illustrating that HR and NHEJ compete to process DNA breaks that arise during DNA replication.

1,482 citations

Journal ArticleDOI
TL;DR: This work reviews the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae and examines recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics.
Abstract: Quorum sensing is a process of cell-cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly. This process enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized. Among the many traits controlled by quorum sensing is the expression of virulence factors by pathogenic bacteria. Here we review the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing mechanisms and how each uniquely controls virulence factor production. Additionally, we examine recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics.

1,482 citations

Journal ArticleDOI
TL;DR: Two computer programs are presented, CTFFIND3 and CTFTILT, which determine defocus parameters from images of untilted specimens, as well as defocus and tilt parameters from image of tilted specimens, respectively, using a simple algorithm.

1,480 citations

Journal ArticleDOI
TL;DR: This work presents a census of 1,542 manually curated RBPs that are analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression, a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.
Abstract: Post-transcriptional gene regulation (PTGR) concerns processes involved in the maturation, transport, stability and translation of coding and non-coding RNAs. RNA-binding proteins (RBPs) and ribonucleoproteins coordinate RNA processing and PTGR. The introduction of large-scale quantitative methods, such as next-generation sequencing and modern protein mass spectrometry, has renewed interest in the investigation of PTGR and the protein factors involved at a systems-biology level. Here, we present a census of 1,542 manually curated RBPs that we have analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression. Our analysis is a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.

1,479 citations


Authors

Showing all 20486 results

NameH-indexPapersCitations
Bert Vogelstein247757332094
Richard A. Flavell2311328205119
Steven A. Rosenberg2181204199262
Kenneth W. Kinzler215640243944
Robert J. Lefkowitz214860147995
Rob Knight2011061253207
Irving L. Weissman2011141172504
Ronald M. Evans199708166722
Francis S. Collins196743250787
Craig B. Thompson195557173172
Thomas C. Südhof191653118007
Joan Massagué189408149951
Stuart H. Orkin186715112182
John P. A. Ioannidis1851311193612
Eric R. Kandel184603113560
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202330
2022228
20211,583
20201,587
20191,591
20181,394