Title: The intersection of development and innate immune system function in Arabidopsis.
NIH RO1GM107444-01
07/01/13-06/30/17
This proposal focuses on the dissection of a plant immune system signaling network that is repeatedly targeted by effectors from pathogens from three kingdoms. We will determine whether the host proteins targeted by multiple pathogen effectors have functions in disease resistance responses, with a particular emphasis on the sub-network featuring a set of transcription factors, called TCPs, that regulate normal development.
Project Summary: Plants are critical for human health and well being. We eat plants, or animals that ate plants before we ate them; we use plant fibers for our clothes and our homes; we rely on plants to provide ecosystems conducive to environmental well being. Plants provide us with oxygen. Without plants, human life would be impossible. Hence, research to understand plant growth, health and productivity is explicitly relevant to human health and well being, as was stressed in the 2009 National Research Council report: ‘A New Biology for the 21st Century: Ensuring the United States Leads the Coming Biology Revolution.’
Plant research contributes significantly to understanding of basic processes in humans. Comparative analyses in plants led to the identification of protein families or domains involved in human disease and development. A majority of human genes suspected or known to play a role in disease have orthologs in plants -- for example, 70% of genes implicated in cancer have plant orthologs. The experimental ease of Arabidopsis genetics, genomics, and cell biology leads to discoveries about fundamental processes shared across all eukaryotes, especially those processes that cross reference normal development with a host’s response to microbial pathogens, the focus of this proposal.
This new project takes advantage of completed NIH supported research that revealed how the effector protein (virulence factor) repertoires from a bacterial and a eukaryotic oomycete pathogen deploy effectors that converge onto an interconnected set of intracellular host targets. This convergence is striking as these two pathogens, which are separated by ~2 billion years of evolution, have very different life styles and virulence mechanisms. These data supported the overall hypothesis that pathogens usurp normal developmental and cell biological process to counteract host immune responses.
In this new proposal, our goal is to understand the functional processes of development and immunity governed by a specific subset of ancient and conserved transcription factors, called TCPs, that are repeatedly targeted by diverse pathogen effectors, and that form a tight sub-network in the current Arabidopsis interactome. TCP proteins are well-characterized regulators of development, but novel players in defense. Thus, this proposal provides a rare opportunity to dissect the molecular mechanism of transcriptional coordination across conflicting developmental and defense cues. TCP genes are an ancient gene family found in pteridophytes, lycophytes, moss and some algal species, representing an evolutionary history of about 650 million years, which enable us to study the trajectory of co-evolution of developmental and immune functions.
Knowledge emerging from our experiments will benefit investigations of animal pathogens, since human pathogens also manipulate normal host cell physiology by targeting critical regulators of normal cell function.