The circadian clock has profound impacts on living organisms on earth. It maximizes the fitness of an organism by enabling it to coordinate metabolism and behavior with its environment. However, studies that unequivocally demonstrate the fitness benefits are scarce and the underlying molecular mechanisms are poorly known. The surprising discovery that the Arabidopsis clock component, CCA1, is a key regulator of RPP4-mediated resistance against the oomycete pathogen Hyaloperonospora arabidopsidis (Hpa) leads to this first in depth study of the interplay between the circadian clock and plant immunity mechanisms.
Aim 1 of this study will focus on the dissection of the regulatory circuitry between CCA1 and the resistance protein RPP4 using molecular genetics and systems approaches. A mathematical model will be made to explain how RPP4 perturbs CCA1-mediated rhythmic expression of defense genes resulting in programmed cell death of the infected cell and resistance to Hpa.
Aim 2 will investigate the role of the circadian clock in systemic acquired resistance to test the hypothesis that the clock is reset during this immune response to redirect the resource to defense and promote cell survival. There are striking parallels between plant defense mechanisms and animal innate immunity. The influence of the circadian clock on animal immune responses has also been reported. However, in depth studies are challenging because of the inherent complexities of animal circadian clocks (central and peripheral) and of the microflora. Therefore, the proposed Arabidopsis-Hyaloperospora study will have a great advantage in revealing the design principles underline the interplay between the circadian clock and immunity besides providing detailed molecular mechanisms. The system perspectives on plants immune mechanisms will help us design better strategies to control crop disease and reduced the use of pesticides, which are hazardous to the environment and human health. Plant health has always had a significant impact on human health as demonstrated by the infamous Irish potato famine in 1840s, which was caused by Phytophthora infestans, a close relative of Hpa used in this study. With the world population exploding, developing better and safer agricultural practices is not a choice, but a necessity.

Public Health Relevance

The circadian clock affects many aspects of human lives including jetlag, obesity, and immunity. However, the molecular mechanisms are poorly understood because humans have the complex central clock in the brain as well as peripheral clocks in different organs. This project will use a simpler organism, thale cress, to study how the circadian controls the timing of plant immune responses against infection and develop new ways to control crop disease and reduce the use of pesticides hazardous to human health and environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM099839-01A1
Application #
8368842
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Sesma, Michael A
Project Start
2012-09-17
Project End
2016-07-31
Budget Start
2012-09-17
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$290,738
Indirect Cost
$100,738
Name
Duke University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Zavaliev, Raul; Dong, Xinnian; Epel, Bernard L (2016) Glycosylphosphatidylinositol (GPI) Modification Serves as a Primary Plasmodesmal Sorting Signal. Plant Physiol 172:1061-1073
Zhou, Mian; Wang, Wei; Karapetyan, Sargis et al. (2015) Redox rhythm reinforces the circadian clock to gate immune response. Nature 523:472-6
Zheng, Xiao-Yu; Zhou, Mian; Yoo, Heejin et al. (2015) Spatial and temporal regulation of biosynthesis of the plant immune signal salicylic acid. Proc Natl Acad Sci U S A 112:9166-73
Saleh, Abdelaty; Withers, John; Mohan, Rajinikanth et al. (2015) Posttranslational Modifications of the Master Transcriptional Regulator NPR1 Enable Dynamic but Tight Control of Plant Immune Responses. Cell Host Microbe 18:169-82
Fonseca, Jose Pedro; Dong, Xinnian (2014) Functional characterization of a Nudix hydrolase AtNUDX8 upon pathogen attack indicates a positive role in plant immune responses. PLoS One 9:e114119