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.

Public Health Relevance

Plants express a sophisticated immune system that relies on both extracellular and intracellular receptors. This is directly analogous to the organization of te receptors in mammalian innate immune systems, including human. We recently defined a plant-pathogen immune system interactome demonstrating that evolutionarily diverged pathogen virulence factors (effectors) converge onto a limited set of host target cellular machinery, including many host transcription factors that normally control various aspects of normal plant cell growth and differentiation. We aim here to explore how plant cells integrate defense and normal development signals, and how pathogens manipulate this signaling intersection to enhance their fitness. Projected results will directly inform basic biomedical research relevant to normal and pathogen-modulated cellular and developmental signaling decisions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM107444-01
Application #
8561801
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Hoodbhoy, Tanya
Project Start
2013-09-01
Project End
2017-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$257,241
Indirect Cost
$86,241
Name
University of North Carolina Chapel Hill
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Belkhadir, Youssef; Yang, Li; Hetzel, Jonathan et al. (2014) The growth-defense pivot: crisis management in plants mediated by LRR-RK surface receptors. Trends Biochem Sci 39:447-56
We├čling, Ralf; Epple, Petra; Altmann, Stefan et al. (2014) Convergent targeting of a common host protein-network by pathogen effectors from three kingdoms of life. Cell Host Microbe 16:364-75