TOR (target of rapamycin) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, and cellular energy. TOR was originally discovered in budding yeast but is conserved in all eukaryotes including plants, worms, flies, and mammals. The discovery of TOR led to a fundamental change in how one thinks of cell growth. It is not a spontaneous process that just happens when building blocks (nutrients) are available, but rather a highly regulated, plastic process controlled by TOR-dependent signaling pathways. TOR is found in two structurally and functionally distinct multi-protein complexes, TORC1 and TORC2, each regulating its own set of downstream effector pathways. The two TOR complexes, like TOR itself, are highly conserved. TORC1 in yeast and mammals mediates temporal control of cell growth by regulating several cellular processes including translation, transcription, ribosome biogenesis, nutrient transport, and autophagy. TORC2 in yeast and mammals mediates spatial control of cell growth by regulating the actin cytoskeleton. Thus, the two TOR complexes constitute an ancestral signaling network conserved throughout eukaryotic evolution to control the fundamental process of cell growth. While the role of TOR in controlling growth of single cells is relatively well understood, a major challenge now is to understand the role of TOR signaling in coordinating and integrating overall body growth and metabolism in multi-cellular organisms. This will require elucidating the role of TOR signaling in individual tissues. As a continuation of our longstanding interest in TOR, the overall goal of the proposed research is to further characterize TOR signaling in yeast and mammals. As a central controller of cell growth and metabolism, TOR plays a key role in development and aging, and is implicated in disorders such as cancer, cardiovascular disease, obesity, and diabetes. Our findings may be of fundamental and medical importance.