A fundamental question in biology, which remains unanswered, is how the environment of the organism regulates its growth and development. Unlike animals, plants neither have specific organs that see or hear various environmental stimuli nor can they move around to avoid adverse conditions. Although lacking a brain, plants can successfully integrate internal and external cues and make appropriate decisions about growth. In contrast to animals, growth in plants occurs post-embryonically, to produce new organs and for growth and modification of existing forms to adapt to the local environment. Light is among the most relevant environmental signals because light not only drives photosynthesis but also provides critical information about the local growth environment as well as diurnal and seasonal time. Over the next few years, my laboratory will address the mechanisms and the nature of inter-organ communication in plants, where in spite of lack of a nervous system, signaling to distant organs occur when exposed to a sub-optimal light environment. Our longterm goal is to understand the molecular mechanisms by which a plant perceives and responds to its light environment. To address our questions, we will use cryptochromes (CRYs), the UV-A/blue light photoreceptor, as they form the interface between the light environment and the organism. CRYs are present in diverse organisms including humans, where they regulate circadian rhythms, several physiological processes and diseases. We will obtain mechanistic insights on CRY regulation of gene expression at a cellular level that leads to morphological changes at the organismal level. We will also determine how light and the newly identified molecular factor, that we have identified controls CRY protein quantity and activity. Also, our research will unravel the novel mechanisms by which CRYs, through its interaction with the RNA-binding proteins that we have discovered, control RNA metabolism specifically that of methylated RNAs (m6A). m6A is a RNA modification that controls its fate as a reversible regulatory mark and disruption of RNA methylation leads to growth defects in plants and is linked to several human diseases. Therefore, uncovering the role of CRYs in RNA metabolism has the potential to contribute to the emerging field of methylated RNA with clinical implications. The success of this study will help to significantly improve crop productivity to feed the growing human population and in the development of optogenetic tools to target neuronal disorders. In humans, disruption of CRY activity is associated with many human disorders including cancer, inflammation, insomnia and diabetes. Understanding CRY function can lead to both prevention and treatment of these diseases. Taken together, our research will have a broad impact on agriculture and in human health and disease.

Public Health Relevance

Cryptochrome (CRY) UV-A/blue light photoreceptors are found in humans and plants where they regulate diverse processes like circadian rhythms, DNA repair, flowering, and growth. In humans, disruption of cryptochrome activity is associated with many disorders including cancer, inflammation, insomnia, and diabetes. The proposed studies aim to determine the molecular mechanisms on how plant cryptochromes interpret light quality and quantity to regulate plant growth. Understanding the mechanisms of cryptochrome signaling will lead to improvement of crop yields and human nutrition. Also, it can lead to prevention and development of therapies for diseases linked to impaired cryptochrome function. Work on plant cryptochromes will contribute to the rapidly growing field of optogenetics, which has far-reaching biomedical applications.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
3R35GM125003-03S1
Application #
9965524
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gaillard, Shawn R
Project Start
2017-08-04
Project End
2022-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724