Paolo Guerra

Systems biologist who tracked TORC1 and PKA signalling in single yeast cells and showed that their growth signals rise and fall with the cell cycle

PhD, University of Groningen (2022, thesis on single-cell analysis of TORC1 and PKA signalling during the budding yeast cell cycle; Andreas Milias-Argeitis group; at the time of the study)

Textbook diagrams show TORC1 (the yeast version of mTORC1) as a switch that is either on, when food is plentiful, or off, when it is not. Paolo Guerra's 2022 paper in the Journal of Cell Science (GUE2022), from Andreas Milias-Argeitis' group at the University of Groningen, looked at single cells instead of averages. Using time-lapse microscopy on hundreds of budding yeast cells, the team followed where two target proteins of TORC1 and of PKA (another nutrient-sensing kinase) sat inside the cell, which shows how active the kinases are. Their activity towards ribosome building rose and fell in step with the cell cycle, even though the food supply stayed the same the whole time. Mutations in regulators upstream of TORC1 and PKA changed the rhythm, which suggests that signals from the cell's own metabolism drive part of it.

For mTOR research this means that growth signalling is not only a reaction to the outside world but also has its own internal timing tied to cell division. The work was done in yeast.

The paper was part of Guerra's 2022 doctoral thesis at the University of Groningen, on single-cell analysis of TORC1 and PKA signalling and how growth and division are coordinated. In the same period Guerra contributed to a neural-network tool that outlines yeast cells in microscope images without hand-labelled training data, and to a 2022 study on what sets the timing of the Start checkpoint that commits a yeast cell to divide. No later position could be confirmed.

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