Robert A Lindquist
Researcher in David Sabatini's group at the Whitehead Institute who ran large image-based RNAi screens for regulators of TORC1 signaling and helped build the CellProfiler image-analysis software
Whitehead Institute for Biomedical Research, Sabatini lab (papers 2006–2011, affiliation at the time of the studies) · current position not confirmed
Robert Lindquist is a co-author on two cell-biology papers from David Sabatini's lab that changed how the field thinks about mTORC1, the growth-control complex. The 2007 paper (SAN2007) found PRAS40, a brake that sits inside mTORC1. When insulin is missing, PRAS40 holds the complex back. Insulin switches on the kinase Akt, Akt tags PRAS40 with a phosphate, and the brake lets go. This helped explain how a hormone sets how strongly mTORC1 works.
The 2008 paper (SAN2008) answered a different question: how does mTORC1 know that amino acids, the building blocks of proteins, are available? The answer was the Rag GTPases, small switch proteins that bind raptor, part of mTORC1. When amino acids are present, the Rags bring mTORC1 to the place in the cell where its activator Rheb sits. Both findings come from experiments in cultured cells.
Lindquist's own line of work in the lab was screening technology. He is first author of a 2011 Genome Research paper that knocked down genes one by one in fruit-fly cells grown on printed microarrays and read the effect on TORC1-S6K signaling by microscope, which found new regulators of the pathway. He was also a co-author of the 2006 Genome Biology paper describing CellProfiler, open-source software that measures cell features in microscope images, and of the 2008 follow-up CellProfiler Analyst. PubMed lists him at the Whitehead Institute in Cambridge, Massachusetts. A current position could not be confirmed from an official source.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2007 | M | PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase SAN2007 Co-author on the cell study that identified PRAS40 as an insulin-controlled brake inside mTORC1. |
| 2008 | M | The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 SAN2008 Co-author on the cell study showing that the Rag GTPases bind raptor and tell mTORC1 that amino acids are present. |
Co-authors in the Atlas 6
People with a profile here who share at least one study with Robert A Lindquist.
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- Carson C. Thoreen 2 shared studies Used Torin1, one of the first ATP-competitive mTOR inhibitors, to reveal functions of mTORC1 that rapamycin cannot block. He then showed that mTORC1 controls translation of mRNAs for the protein-making machinery mainly through the 4E-BP proteins
- David M. Sabatini 2 shared studies Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
- Timothy R. Peterson 2 shared studies Discovered DEPTOR, an inhibitor that binds mTOR in both complexes and is overexpressed in some multiple myelomas. He also showed that mTORC1 controls fat synthesis by regulating where the enzyme lipin 1 sits in the cell, and through it the SREBP pathway
- Yasemin Sancak 2 shared studies Showed as a Sabatini-lab graduate student, in parallel with Kun-Liang Guan's lab, that the Rag GTPases relay amino-acid signals to mTORC1, and that Ragulator anchors them to the lysosome where mTORC1 is switched on. She also identified PRAS40 as an insulin-regulated inhibitor of mTORC1
- Liron Bar-Peled Showed as a Sabatini-lab graduate student that Ragulator switches the Rag GTPases on, acting as their GEF. He also discovered GATOR1 and GATOR2; GATOR1 switches the Rags off and its genes are mutated in some cancers
- Seong A. Kang Contributed to the Sabatini-lab studies that identified PRAS40 and DEPTOR, two of the cell's own mTOR inhibitors, and to the first characterisation of the mTOR inhibitor Torin1
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