Oliver's research focus

Related studies — current research focus

The foundational and most closely related studies behind the “pattern over time, not just average level” question above, ranked by scientific significance rather than publication date:

Year	Evidence	Study	Authors
2026	M	Inferring feedback regulation from static snapshots of a single signal A method for reading a signal’s change over time out of still images — and it finds AKT feedback that exists only in a narrow window at G1/S, which the authors attribute to mTORC1/S6K1→IRS1 while stating their data do not establish that edge uniquely.	Ginzberg M Kafri R
2026	M	Mathematical modeling of dietary timing- and protein quality-responsive liver circadian clock and its function on ribosome biogenesis Treats mTORC1 as a rhythm set by the timing and quality of amino acid intake rather than a fixed level, and asks what the shape of that rhythm does to ribosome biogenesis. A prediction, not a measurement — the model is in silico.	Lu L Androulakis IP
2026	M	Fluorescent protein ticker tape (FPTT): Multiplexed recording of transcriptional dynamics in living cells and in vivo A new multiplexed live-cell biosensor platform that, built and validated independently of JOS2024, directly visualized mTOR activity oscillating across the cell cycle — orthogonal confirmation that the pattern of mTOR signaling over time is a real, reproducible phenomenon rather than an artifact of one assay.	Wang R JJJiang J
2024	M	mTORC1 activity oscillates throughout the cell cycle, promoting mitotic entry and differentially influencing autophagy induction The paper that sparked this focus — mTORC1 activity is lowest in mitosis/G1 and highest in S/G2, and this timing, not just average level, shapes autophagy sensitivity.	Joshi JN Valvezan AJ
2020	M	AIMTOR, a BRET biosensor for live imaging, reveals subcellular mTOR signaling and dysfunctions The enabling technology behind the question. AIMTOR reads mTOR activity live in single cells and separately in the cytosol, at the lysosome, in the nucleus and near mitochondria — which is what turns a pulsatile or oscillatory hypothesis from something arguable into something measurable. It came five years after TORCAR (ZHO2015), the first live mTORC1 reporter, and adds compartment-specific versions in a bioluminescence format.	Bouquier N Ollendorff V
2019	R	Molecular logic of mTORC1 signalling as a metabolic rheostat Conceptual framework from Joshi 2024's own senior author — mTORC1 as a graded rheostat rather than an on/off switch.	Valvezan AJ Manning BD
2017	M	mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability Same lab's translational angle — TSC-mutant cells' nucleotide synthesis as a druggable weak point.	Valvezan AJ Manning BD
2015	A	Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system One of two studies in this corpus that hold the compound constant and vary only when it is given (the other, OKA2013, varies the time of day): weekly or every-fifth-day rapamycin spared glucose tolerance, beta-cell function and the immune system that daily dosing impaired, while still inhibiting mTORC1. Read the scope honestly — this is organismal pharmacology rather than cell-level signalling, and it measured side effects, not benefit. It belongs here because it is the same claim in a different register: the pattern, not the average, decided the outcome.	Arriola Apelo SI Lamming DW
2015	M	Dynamic Visualization of mTORC1 Activity in Living Cells The first genetically encoded reporter of mTORC1 activity: a FRET sensor that shows mTORC1 changing in living cells, in real time and compartment by compartment. It found activity in the nucleus and at the plasma membrane as well as at the lysosome, with different signals lighting up different places. Without a live reader, the question of whether the pattern matters could not be asked of mTORC1 at all.	Zhou X Zhang J
2014	M	Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome Closest mechanistic precedent to the “timing, not just level” question — shows TSC complex localization, not just abundance, gates mTORC1.	Menon S Manning BD
2012	M	TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1 Completed the parts list of the TSC complex whose GAP activity Joshi 2024 studies across the cell cycle.	Dibble CC Manning BD
2012	M	Temporal coding of insulin action through multiplexing of the AKT pathway The cleanest cell-level proof that timing carries information in this pathway: a pulse of insulin and a sustained dose became transient and sustained AKT signals, and S6K answered only the transient one. It sits one step upstream of mTORC1 and uses a rat liver cell line, so it is not mTORC1's own rhythm. What it shows is the principle the question rests on: same pathway, same molecules, and the shape of the signal decides which output responds.	Kubota H Kuroda S
2011	M	Lysosomal positioning coordinates cellular nutrient responses The spatial counterpart to Menétrey 2014, one storey up: with nutrients available lysosomes move out to the cell periphery and mTORC1 is active there; starvation pulls them into a cluster around the nucleus, output falls and autophagy is released. Where the compartment sits, not how much of it there is, carries the signal — and it sets the rate of autophagy directly.	Korolchuk VI Rubinsztein DC
2003	M	Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb Founding paper — first to show TSC1/TSC2 acting as the GAP complex for Rheb, the discovery the whole TSC→mTORC1 axis rests on.	Tee AR Cantley LC
2003	M	Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling Companion founding paper, published independently and simultaneously with Tee et al. 2003 — same weight, same discovery.	Inoki K Guan KL
2002	M	TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling Established the Akt→TSC2→mTOR link — the exact “known regulatory input” Joshi 2024 shows is bypassed during interphase.	Inoki K Guan KL

On the horizon

Not yet part of the graded corpus above — because they are either still running or have not been peer-reviewed — but directly relevant, found via ClinicalTrials.gov and bioRxiv:

Labs working on this

Research groups whose work bears most directly on the question above, grouped by how they get at it. Each one links to the lab's own page; photos link to the lab head's profile in the Atlas.

Measuring how mTOR activity changes over time, and what that timing does

• 
  Valvezan Lab

  Piscataway, NJ, USA Rutgers University (CABM)

  Alexander J. Valvezan

  Showed that mTORC1 activity rises and falls through the cell cycle, and that cells low in mTORC1 during G1 are pushed into autophagy more easily. This is the study the whole focus grew out of.

• 
  Kafri Lab

  Toronto, Canada The Hospital for Sick Children (SickKids)

  Ran Kafri

  Studies how mTORC1 sets a target size for cells, and built a method for reading how a signal changes over time out of fixed snapshots.

• 
  Albeck Lab

  Davis, CA, USA University of California, Davis

  John G. Albeck

  Films mTORC1–TFEB, AMPK and AKT signalling in single living cells and showed that mTORC1 output adjusts continuously as nutrients change.

• 
  Milias-Argeitis Lab

  Groningen, Netherlands University of Groningen

  Andreas Milias-Argeitis

  Showed in single yeast cells that TORC1 activity oscillates with the cell cycle even when nothing outside the cell changes, a yeast counterpart to the Valvezan result.

• 
  Cappell Lab

  Bethesda, MD, USA National Cancer Institute (NIH)

  Steven D. Cappell

  Found that mTOR briefly switches off the APC/C as a cell starts to divide, creating a short pulse of glycolysis the cell needs to get going.

• 
  Kuroda Lab

  Tokyo, Japan The University of Tokyo

  Shinya Kuroda

  Showed that different time courses of insulin are read out by different branches of the AKT pathway, S6K among them: an early, direct demonstration that the shape of a signal carries information, not just its level.

• 
  Zebrafish Neurogenetics Unit (Bally-Cuif)

  Paris, France Institut Pasteur

  Laure Bally-Cuif

  A 2026 preprint from the lab reports that mTORC1 sets the tempo at which dormant neural stem cells in the adult zebrafish brain move toward activation.

• 
  Scadden Lab

  Boston, MA, USA Massachusetts General Hospital & Harvard Stem Cell Institute

  David T. Scadden

  Imaged mTORC1 activity in leukaemia cells inside live mice and found that inhibiting mTORC1 at one particular moment during chemotherapy kills more cancer cells.

Tools for watching mTOR activity live

• 
  Zhang Lab

  La Jolla, CA, USA University of California San Diego

  Jin Zhang

  Built TORCAR, a FRET biosensor that shows mTORC1 activity in living cells as it happens, including in separate parts of the cell.

• 
  Perroy & Ollendorff teams

  Montpellier, France IGF (CNRS/INSERM) and DMEM (INRAE), University of Montpellier

  Julie Perroy & Vincent Ollendorff

  Co-developed AIMTOR, a BRET biosensor that reads mTOR activity live in single cells and in compartments such as the lysosome and the nucleus.

• 
  Ktistakis Group

  Cambridge, UK Babraham Institute

  Nicholas T. Ktistakis

  Filmed mTORC1 moving to lysosomes within two minutes of adding amino acids, before its targets are phosphorylated.

Rhythm and dosing in the whole organism

• 
  Kondratov Lab

  Cleveland, OH, USA Cleveland State University

  Roman V. Kondratov

  Found that mTOR activity in the liver follows a daily rhythm set by feeding, and compares calorie restriction with cycles of fasting and refeeding.

• 
  Androulakis Lab

  Piscataway, NJ, USA Rutgers University

  Ioannis P. Androulakis

  Models liver mTORC1 as a rhythm set by when and what an animal eats, and asks what that rhythm does to ribosome production.

• 
  Lamming Lab

  Madison, WI, USA University of Wisconsin–Madison

  Dudley W. Lamming

  Showed that rapamycin given once every five days still extends mouse lifespan with fewer side effects, so the dosing schedule matters, not just the dose.

• 
  Partridge Lab

  London, UK UCL Institute of Healthy Ageing (and MPI for Biology of Ageing, Cologne, emerita)

  Linda Partridge

  Showed that a brief course of rapamycin in early adulthood gives lasting protection against ageing, and that intermittent rapamycin feeding keeps the lifespan benefit.

Frontier questions

Five open framing questions in the Atlas grow directly out of this — not gaps in what has been measured, but questions about whether the standard way of measuring mTOR is even asking the right thing:

• Primary Does mTORC1 carry information in the pattern of its activity over time, not its average level?
  Nearly every study measures mTOR activity the way you would read a thermometer once: a single number, from a single moment, usually right after the cell was given a sudden jolt of nutrients. But real cells never get a sudden jolt. They get meals, exercise, sleep and waking — a rhythm. If what matters is the rhythm rather than the average, then the standard measurement is not just imprecise. It is answering a different question from the one being asked.
• Is mTOR signalling decided by where the complex is active, rather than by how much of it is active?
  The lysosome is normally described as mTOR's parking space. Newer structural work describes it more like a workbench: what the enzyme can reach depends on how it is docked. If that is right, two cells with the same amount of activity can be doing completely different jobs — and grinding them up to measure the total would hide exactly that.
• Does the timing of mTOR inhibition have to match the body's own pulses — feeding, exercise, sleep?
  Giving the drug once a week instead of daily is usually explained as a way to lower the dose and avoid side effects. But if the pathway cares about rhythm, the question is not how often you give it — it is whether the gaps in the drug line up with the moments the body actually needs the pathway on, like after a meal or after exercise. Nobody has tested that alignment.
• Is mTORC1 one pathway or several separable outputs — and which of them carries ageing?
  Most of the argument is about how hard to press the brake, and recently about which of the two brakes to press. Hardly anyone asks which of the things the brake controls actually needs slowing. And those things do come apart: in muscle, fixing one downstream branch rescues the problem while removing another does nothing.
• Which human ageing phenotypes are causally reversible by mTOR modulation — and is it the same mechanism in each tissue?
  Asking whether a drug makes people live longer cannot be answered in any reasonable amount of time, and aiming at it has crowded out better questions. Ageing is not one thing: the immune system, muscle, metabolism and the brain each age in their own way, and a drug might reach some of them and miss others entirely.