Innovation in plant signaling network - nutrient signaling integrates and coordinates gene expression, metabolism, growth, and stress- immune responses

The National Institute of General Medical Sciences awarded The General Hospital Corporation (Massachusetts General Hospital) $453,750 on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to investigate novel molecular mechanisms of nutrient signaling networks in plants, specifically exploring how Target-of-Rapamycin (TOR) signaling promotes growth and development while repressing stress-innate immunity, and to characterize calcium-sensor protein kinases (CPKs) and their roles in nitrate signaling. The research uses Arabidopsis thaliana as a model organism to address fundamental gaps in understanding glucose and nitrate signaling mechanisms that integrate gene expression, metabolism, growth, and stress-immune responses across multicellular organisms. Work is performed in Boston, Massachusetts, with a period of performance from September 1, 2026, through April 30, 2031. This Project Grant is classified as an investigator-initiated award under NIGMS's basic research portfolio, supporting the Institute's mission to increase understanding of biological processes that lay the foundation for advances in disease diagnosis, treatment, and prevention.

In multicellular organisms, growth factors and hormones are ineffective in growth promotion without the support of nutrient signaling networks. However, surprisingly little is known about the primary nutrient signaling mechanisms in plants and animals. Plants play a central role in bridging the conversion of inorganic CO2, H2O, and nitrate to organic sugars and n-molecules in the global carbon and nitrogen cycles by photosynthesis and by assimilating nitrate to generate sugars, lipids, amino acids, nucleic acids, vitamins, and diverse organic carbon-nitrogen molecules, which are essential to build and sustain lives from plants to humans. Despite the fundamental and multifaceted regulatory roles of glucose and nitrate in gene expression, metabolism, growth, and development, the diverse and precise molecular and cellular mechanisms of glucose and nitrate signaling remain largely elusive in higher plants. Hampered by gene redundancy and mutant lethality, classical genetic screens had limited success in identifying key glucose and nitrate signaling regulators in plants over the past decades. Although target-of-rapamycin (TOR)-regulated translation, metabolism, and autophagy have been extensively studied in animals and glucose and nitrate activate TOR signaling in plants, the molecular mechanisms underlying how TOR kinase directly controls cell proliferation, biomass, development, and stress signaling remain incompletely understood in multicellular organisms. Our research will explore novel molecular mechanisms of the opposite and distinct functions of TOR signaling in promoting growth and development but repressing stress-innate immunity using the plant model arabidopsis thaliana. For nitrate signaling, we have discovered surprising molecular links between specific CA2+-sensor protein kinases (cpks) and the dual functions of nodule inception-like proteins (nlps) as nitrate sensors and transcription factors in plant nitrate-signaling networks. We will build on our new findings and innovative experimental platforms to elucidate the molecular and cellular basis of the nutrient-growth networks that orchestrate system-wide transcriptome and translatome to modulate plant developmental processes. We will integrate complementary strategies and molecular, cellular, biochemical, functional genomic, chemical genetic, and systems analyses to advance our understanding of comprehensive nutrient and stress signaling mechanisms. The proposed research will establish new paradigms for TOR functions as the master integrator of nutrient and stress signaling and discover the actions of nitrate sensor complexes, nutrient-mediated CA2+ signaling, as well as transcriptional, translational, and developmental regulations with sustained scientific impact beyond plant biology.