Oliver's mTOR Atlas Evidence Platform
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Roberto Zoncu

Showed as a postdoc that mTORC1 senses amino acids from inside the lysosome, through the v-ATPase and Ragulator. His Berkeley lab has since mapped how the Rag GTPases and the folliculin complex switch mTORC1 on, and how lysosomal cholesterol feeds into the same system

Professor, UC Berkeley (Molecular & Cell Biology) · postdoc with David Sabatini · PhD, Yale · neuroscience, University of Pisa · Born in Sardinia, Italy

Zoncu Lab, UC Berkeley (Berkeley, California, USA) ↗ Lab lineagetrained under David M. Sabatini → Bluesky@robzonculab.bsky.social ↗ ORCID0000-0003-1611-1891 ↗

Roberto Zoncu Portrait: Cornell University, Weill Institute for Cell and Molecular Biology

Roberto Zoncu grew up in Sardinia in a family of physicians and studied neuroscience at the University of Pisa before crossing the Atlantic for a PhD in cell biology at Yale. He then joined David Sabatini's lab at the Whitehead Institute as a postdoc, turning his skill in live-cell imaging on a question nobody had answered: how does mTORC1 actually 'know' that amino acids are present inside the cell?

Zoncu helped show that mTORC1 is recruited to the surface of the lysosome — the cell's recycling organelle — by the Ragulator–Rag docking complex, and that amino acids inside the lysosome are read out from the inside by the v-ATPase proton pump, an 'inside-out' sensing mechanism. Since starting his own lab at UC Berkeley in 2014, he has extended this picture to cholesterol sensing and to how faulty lysosomal mTORC1 signalling contributes to neurodegenerative disease.

The timeline below traces Zoncu's studies gathered in this Atlas.

Milestones in the Atlas

A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.

YearEvidenceStudy
2010 M Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids SAN2010 Co-discovers that the Ragulator-Rag complex docks mTORC1 onto the lysosomal surface — the physical site where nutrient sensing happens.
2010 R mTOR: from growth signal integration to cancer, diabetes and ageing ZON2010 Authoritative review of mTOR from growth-signal integration to disease.
2011 M mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase ZON2011 Shows mTORC1 reads amino-acid levels from inside the lysosome via the v-ATPase, an 'inside-out' sensing mechanism.
2012 A Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival EFE2012 Rag-GTPase control of mTORC1 is essential for neonatal autophagy and survival to fasting.
2012 M Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1 BAR2012 Ragulator was reported as a guanine-nucleotide exchange factor for RagA/B on the lysosome; later work places Ragulator's exchange activity on RagC and assigns RagA GTP loading to SLC38A9, so the tethering role is the better-established one.
2012 M A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB SET2012 A lysosome-to-nucleus mechanism uses mTOR-dependent TFEB phosphorylation to sense lysosomal state.
2013 M The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 TSU2013 FLCN-FNIP is a GAP for RagC/D; GDP-bound RagC/D is required for the Rag heterodimer to bind mTORC1, promoting its lysosomal recruitment and activation by amino acids.
2015 M Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1 WAN2015 The lysosomal transporter SLC38A9 signals arginine sufficiency to mTORC1.
2016 M Dynamics of mTORC1 activation in response to amino acids MAN2016 Live imaging shows mTORC1 moves to lysosomes within 2 minutes of amino acid addition and peaks by 5 minutes, in step with leucine arriving in lysosomes; phosphorylation of classic mTORC1 targets lags behind, suggesting mTORC1 passes briefly through the lysosome before acting on substrates elsewhere.
2017 M Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex SUX2017 Hybrid structural model of the RagA/C-Ragulator mTORC1 activation complex.
2018 M A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffold LAW2018 A nutrient-induced affinity switch in the Rag-Ragulator scaffold controls mTORC1 lysosomal recruitment.
2019 M Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex LAW2019 Solves the structural mechanism of a Rag GTPase activation checkpoint involving the lysosomal folliculin complex.
2023 R The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease GOU2023 Authoritative review of the molecular basis of nutrient sensing and signalling by mTORC1 in disease.
2026 M A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation. ESP2026 Co-author identifying a nutrient-independent lysosomal TBK1/ULK1 pathway that inhibits FLCN to release TFEB, hijacked by ATP6V1B2 mutations in follicular lymphoma.

Co-authors in the Atlas 35

People with a profile here who share at least one study with Roberto Zoncu.

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  • David M. Sabatini 8 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
  • Liron Bar-Peled 5 shared studies 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
  • James H. Hurley 4 shared studies Structural biologist who uses cryo-EM to show how protein machines assembled on membranes control autophagy and nutrient signalling. His lab solved structures of the Rag–Ragulator complex and of the whole mTORC1–TFEB–Rag–Ragulator assembly on the lysosome
  • Alejo Efeyan 3 shared studies Showed that the Rag GTPases, which relay amino-acid signals to mTORC1, are a life-or-death switch for newborn mice surviving the fast before their first feeding
  • Do Jin Kim 3 shared studies Structural biologist, now at Denali Therapeutics, who worked in James Hurley's lab at UC Berkeley on the protein machines of autophagy and on the Rag-Ragulator complex that brings mTORC1 to the lysosome
  • Andrea Ballabio 2 shared studies Discovered that the transcription factor TFEB is a master switch for building lysosomes (SAR2009) and for autophagy. His lab was one of the groups that showed in 2012 that mTORC1 keeps TFEB out of the nucleus from the lysosome surface, and later (2020) that constitutive TFEB activation drives the kidney disease of Birt-Hogg-Dubé syndrome
  • Choah Kim 2 shared studies Researcher in David Sabatini's lab at the Whitehead Institute who contributed to three studies on how amino acids at the lysosome are sensed by mTORC1
  • Lynne Chantranupong 2 shared studies Showed as a Sabatini-lab graduate student that the Sestrins act through GATOR2 to regulate amino-acid signalling to mTORC1. She then discovered the CASTOR proteins, the cell's arginine sensors for the pathway
  • Rachel L. Wolfson 2 shared studies Identified Sestrin2 as the direct leucine sensor of the mTORC1 pathway as a Sabatini-lab MD-PhD student. She also co-discovered KICSTOR, the complex that recruits GATOR1 to the lysosome
  • Rosalie E. Lawrence 2 shared studies Working in Roberto Zoncu's lab, uncovered the nutrient-driven affinity switch and the FLCN checkpoint that gate mTORC1 activation at the lysosome
  • Shuyu Wang 2 shared studies Co-discovered SLC38A9 as a Sabatini-lab MD-PhD student, a lysosomal amino-acid transporter that signals arginine sufficiency to mTORC1
  • Tim Wang 2 shared studies Co-developed genome-wide CRISPR screening in human cells (reported in parallel by Feng Zhang's lab) as a graduate student with David Sabatini and Eric Lander, and contributed to studies showing that the 4E-BPs mediate mTORC1's control of translation and that CASTOR1 senses arginine
  • 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
  • Zhi-Yang Tsun 2 shared studies Biologist who, as first author in David Sabatini's lab, showed that the tumour suppressor folliculin is a GAP for the RagC and RagD GTPases that carry the amino acid signal to mTORC1
  • Alessandra Esposito Lysosomal signalling and TFEB regulation
  • Alessia Calcagnì TIGEM researcher on the TFEB/TFE3 side of mTORC1 signalling; co-author on the lysosomal stress route to TFEB activation and on mouse models separating mTORC1 from TFEB/TFE3 in kidney cysts and tumours.
  • Andrew L. Markhard Contributed, as a Sabatini-lab researcher, to the discovery that Ragulator docks mTORC1 on the lysosome, and now studies metabolite signals that tell the body it has eaten
  • Ashley M. Thelen Cell biologist who did graduate work in Roberto Zoncu's lysosome lab at UC Berkeley, first author of a 2017 review on the lysosome's roles in lipid metabolism, and later a postdoctoral scholar in Philip Greenberg's lab at Fred Hutch
  • Carmine Settembre Showed, as first author in Andrea Ballabio's lab, that TFEB drives autophagy as well as lysosome production, and, in parallel with other groups, that mTORC1 phosphorylates TFEB at the lysosome to keep this program switched off when nutrients are plentiful
  • Claire Goul Cell biologist who did graduate work in Roberto Zoncu's lab at UC Berkeley on lysosomes and mTORC1, first author of a major review of how mTORC1 senses nutrients and of a 2026 Nature study on how damaged lysosomes are repaired, now a scientist at CZ Biohub
  • Diego L. Medina Cell biologist at the Telethon Institute of Genetics and Medicine in Naples who showed how TFEB, the master switch for lysosome genes, is controlled by calcium released from lysosomes, and who works on lysosomal storage diseases
  • Elizabeth D. Yuan Second author on the study showing that S6K1 phosphorylates BMAL1 to link mTOR signalling with circadian protein synthesis, and co-author on the follow-up in tuberous sclerosis models.
  • Eric Spooner Manager of the Whitehead Institute's Proteomics Core Facility, whose mass spectrometry work identified proteins in complexes for many Whitehead studies, including two on amino acid sensing upstream of mTORC1
  • Gennaro Napolitano mTORC1-TFEB lysosomal signalling
  • Gregory A. Wyant Showed that the lysosomal protein SLC38A9 exports leucine and other essential amino acids out of the lysosome, letting cells grow on proteins they have taken up and broken down there
  • Chun-Yan Lim Cell biologist who trained in Roberto Zoncu's lab at UC Berkeley on how cholesterol controls mTORC1, and now publishes as corresponding author from Guangzhou National Laboratory on lysosome signalling in immunity and nutrient sensing
  • Jlenia Monfregola TIGEM postdoc and co-author on the cryo-EM structure of the mTORC1–TFEB–Rag–Ragulator megacomplex and on the TBK1/ULK1 lysosomal stress route to TFEB.
  • Jörn Dengjel Mass-spectrometry proteomics specialist in autophagy and protein homeostasis; co-author on the TBK1/ULK1–TFEB lysosomal stress pathway and on the spermidine lifespan and cardioprotection study.
  • Kuang Shen Solved, as a Sabatini-lab postdoc, cryo-EM structures of GATOR1 and of the FLCN–FNIP2–Rag–Ragulator complex, two switches that set mTORC1 activity. His UMass Chan lab studies the structural basis of nutrient sensing
  • Maria Manifava Cell biologist in Nicholas Ktistakis's group at the Babraham Institute whose live-cell imaging work spans more than two decades of research on lipid signalling, autophagosome formation and mTORC1
  • Ming-Yuan Su Structural biologist who solved cryo-EM structures of lysosomal complexes in James Hurley's lab at UC Berkeley and now leads cryo-EM studies of mTORC1 regulators as corresponding author at the Southern University of Science and Technology in Shenzhen
  • Nicholas T. Ktistakis Uses live imaging to follow the first minutes of autophagy and of mTORC1 activation
  • Ofer Moldavski Researcher who worked on lysosomes and lipid signalling in Roberto Zoncu's lab at UC Berkeley and was first author of a 2021 study on how the oxysterol 4beta-hydroxycholesterol switches on fat-making genes
  • Rachel M. Jansen First author of the cryo-EM structure showing how the arginine sensor CASTOR1 binds the GATOR2 cage when arginine is low and is released when arginine returns
  • Tuong Huynh Research associate at Baylor College of Medicine in Houston and co-author on a long run of papers from Andrea Ballabio's group on TFEB, the master switch for lysosome and autophagy genes, including the work that tied TFEB to mTOR, starvation and fat metabolism

Every researcher with a profile →

On the programme

Meetings in the Atlas calendar where Roberto Zoncu is listed among the speakers or organisers.

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