Oliver Barton has released mTOR Atlas, a guide to 322 studies of the cellular system targeted by rapamycin
Oliver Barton has released mTOR Atlas, a guide to 322 studies of the cellular system targeted by rapamycin
Atlas version 1.0.0 was released on August 22. It covers 45 topics, and each study is annotated with its model, intervention, and measured outcome, making it possible to match the publication to the question it addresses.
The term “rapamycin” brings together findings from cells, animals, and human studies, although these represent distinct levels of evidence within the same discussion. mTOR is both a protein and the signaling system named after it. Through this system, nutrient availability affects cell growth, protein synthesis, and autophagy, the process by which cells recycle their components. Cell culture experiments clarify the mechanism. Animal experiments test it in a whole organism. Human studies measure outcomes in people.
For every study, the Atlas index provides a link to the original publication, the model, the intervention, and the outcome. Two classification schemes serve different purposes. The pyramid indicates how closely the evidence relates to an outcome measured in humans, while levels A through D distinguish different types of evidence. In the open dataset, 29 level B studies involved humans, 84 level C studies involved animals, and 205 level D entries consist of mechanistic studies and reviews. This classification helps readers interpret a result in light of the experimental conditions. For example, in an experiment with flies, the same dose of rapamycin had opposite effects on lifespan under different diets. Questions about rapamycin can therefore be divided into specific parts: which mTOR complex was affected, which dosing regimen was used, which model was studied, and what was measured.
One of the ten open question pages concerns mTORC1 and mTORC2, the two protein complexes in this system. The page separates established findings from a proposal labeled a “reasoned hypothesis” about a rapamycin regimen that inhibits mTORC1 while sparing mTORC2. To test this hypothesis, Atlas proposes a mouse experiment comparing lifespan, insulin sensitivity, and mTORC2 activity under different rapamycin regimens.
In this way, Atlas connects each paper to its model and measured outcome, and connects each open question to an experiment that could test it.