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Using quantitative genetic screens, researchers from Professor Sebastian Nijman’s lab learn more about the regulation of a key growth control pathway.

mTORC1 is a complex made up of many proteins that controls several vital processes in the cell including protein synthesis and the cellular recycling process, autophagy. Because fine-tuning of these processes is important, mTORC1 is part of a complicated network of regulatory pathways. While research over several decades has pieced together many links in this network, there are still some aspects that are not fully understood.

In order to discover more about mTORC1 regulation, Erica De Zan and colleagues from Sebastian Nijman’s lab at Ludwig Oxford and Thijn Brummelkamp’s lab at the Netherlands Cancer Institute carried out a set of genetic screens in haploid human cells. By investigating the mTORC1 signalling pathway in presence of drugs and genetic alterations, their paper published in Science Signaling, describes for the first time the differential requirement for the Ragulator complex subunits LAMTOR4 and LAMTOR5, depending on the cell’s nutrient status. Ragulator is involved in transport inside the cell and is a known regulator of mTORC1. The researchers also identified a previously unknown genetic interaction between the tumour suppressor FLCN and LAMTOR4, which could be harnessed for a future cancer therapeutic strategy.