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NIHNATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESR35

The Role of Cryptochromes in environmental regulation of growth

Active
Institution
COLD SPRING HARBOR LABORATORY, NY
Principal investigator
Vincent U Pedmale
Funding
$518K
Duration
2017–2029
Open portfolio

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Abstract

ABSTRACT A fundamental question in biology that has yet to be answered is how an organism's environment 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 the growth and modification of existing forms to adapt to the local environment. Light is among the most relevant environmental signals because it not only drives photosynthesis but also provides critical information about the local growth environment as well as diurnal and seasonal timing. Over the next few years, my laboratory will aim 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 photoreceptors, 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 and several physiological processes, like metabolism, growth, and magnetoreception. We will obtain mechanistic insights on how CRY regulates gene expression at the cellular level, which leads to morphological changes at the organismal level. We will also determine how light and the newly identified CRY2-associated molecules that we have discovered function in CRY-mediated signaling pathways. Also, our research will unravel the novel mechanisms by which CRYs, through their interaction with the RNA-binding proteins that we have discovered, control RNA metabolism, specifically that of methylated RNAs (m6A). m6A is an 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. We will also address how CRYs integrate environmental signals and modify chromatin through their interaction with chromatin remodelers, whose findings will fill a large void in this field. The success of this study will significantly improve crop productivity to feed the growing human population and aid 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 human health and disease.

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R35NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESMaximizing Investigators' Research Award C Study Section[MRAC]modificationorganismdisruptionlightplantsorgansgrowthrna

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