Michign State University,PhD
Complex biology is a new paradigm in biology; many of biological phenomena can be understood as emergent properties that arise from the complex system. Complex biology research group is striving to understand how complex webs of direct and indirect interactions of various molecules such as DNA, RNA, and proteins have developed, and how the spatial and temporal interactions underlie the emergent biological processes.
One of the major questions in our group is how time is incorporated into aging process along lifespan and how aging process is regulated at a systems level. Arabidopsis thaliana has been used as our primary model system to understand how plants know when and how to die. Toward understanding the temporal-spatial dynamics of functional and regulatory transitions throughout life history, we are employing systems level analyses including NGS and computational approaches in Arabidopsis. One of our new technological challenges is integration of phenome with other -omics data along lifespan and its application in understanding the evolutionary mechanism of aging and senescence. Senescence and death is in part systemically controlled at the organismal level. We are employing rice as a model system to understand the mechanism underlying the systemic senescence. We are also studying interaction of the two plant timing mechanisms, aging and circadian clock.
Complex biology research group is extending our aging research into animal aging to reveal the time-dependent changes of spatial, temporal molecular and informational webs along the aging process of animal system including mice and worms.
Plant Senescence and Life History
Plant senescence and the concomitant death are among the most dramatic developmental events we encounter in nature, as we observe during whole plant death of several crop plants and during the death process of autumn leaves. Plant senescence and death have a biological “purpose”. Plants accumulate nutrients during the growth phase through carbon fixation and, at the senescence stage, relocate the nutrients to other organs such as developing seeds as a part of the parental investment. Thus, senescence and death in plants are evolutionarily acquired developmental strategies for better fitness. The senescence process is also critically important for humanity: Plants are the primary source of food on earth and the senescence process involving the disassembly and relocation of the nutrients is responsible for production of many important foods such as rice, corn, and wheat, etc. In fact, what we eat mostly are nutrients primarily derived from senescing leaves of crop plants. As the senescence process is critical for fitness of plants, when to die and how to die are under intricate genetic program integrating information on age of plants and organs as well as on environmental and endogenous effectors.
Our overall goal is to gain insights into system-level understanding of senescence and cell death processes in plants from the aspect of life history strategy at molecular, cellular, intercellular, organ and organismal levels and thereby to obtain breakthrough knowledge to improve plant productivity.
Specific Research Aims
– Identification of spatio-temporal network dynamics with finding of key regulatory modules during life history and senescence
– Identification of key molecular and cellular mechanisms regulating senescence and death in the context of life history strategy
– Understanding interaction of endogenous and exogenous signals with life history and senescence
– Understanding evolution of senescence and death in plants
A. Multi-dimensional transcriptome analysis of the Arabidopsis leaf along lifespan
Leaves, during their lifespan, undergo developmental, physiological, and metabolic shifts, ending with senescence and death. The developmental shifts during the leaf lifespan involve temporal changes in expression of multiple types of RNA, contributing to age-dependent functional and regulatory shifts. We have performed comprehensive analyses of Arabidopsis transcriptomes over the entire lifespan of the leaf organ, using total RNA and small RNA sequencings. Comparison of the regulatory processes between the growth phase and the aging phase showed that the aging in plant is a highly coordinated process via multi-layered regulatory networks involving various types of regulatory RNAs.
- Comprehensive analysis of Arabidopsis transcriptomes over the entire lifespan of the leaf organ, using total RNA and small RNA sequencings.
– Functional analysis of senescence regulatory factors including transcription factors and non-coding RNAs
– Understanding functional and regulatory transition throughout the life history
B. Temporal dynamics of molecular networks along life history and senescence
Aging and senescence are induced by an extensive range of developmental and environmental signals and controlled by multiple, cross-linking pathways. Elucidation of this complex process requires the systems-level view of molecular networks and network modules, overcoming the current, individual component-based view. Furthermore, aging and senescence are not static, but dynamic process, which are regulated by temporal changes of molecular networks for the functional and regulatory transition of cells, organs, and organisms. Thus, identification of the multilayered networks and key modules encoding senescence processes throughout life history will be a crucial next step toward better understanding of senescence and death processes.
– Network dynamics along life history and senescence
System-level understanding the integrated network for multi-gene family underlying aging
– Regulatory modules associated with life history and senescence
Understanding evolutional principles of functional network modules to increase adaptability of a system and to allow rapid/robust informational flow through the network
– Functional and regulatory transition along life history and senescence:
Studying how the NAC transcriptional factor networks are shifting along the life span and how the network transition controls aging process
C. Dynamics of nuclear architecture along leaf aging
The organization of chromatin in the nucleus is important for transcription coordination required for many biological functions both in animals and plants. It has been broadly accepted that the packing of chromatin in the nucleus is not random but structured at several hierarchical levels. During leaf aging, epigenetic change of chromatin including decondensation of heterochromatin and histone modification occurs in the nuclei. We hypothesize that topological changes of chromatin take place in a regular and orderly pattern, resulting in transition of developmental program along leaf aging. Thus, we will investigate how topological properties of chromatin are involved in reprogramming of transcriptional regulation along leaf aging.
– Identification of structural modules at chromatin level in Arabidopsis
– Investigation of topological changes in chromatin on transcriptional coordination during leaf aging
– Identification of regulatory elements involved in transition of chromatin structural modules during leaf aging
D. Natural adaptation contributed by lifespan-controlling programs
Lifespan controlling programs in plants increase their fitness in local habitats by adjusting their programs to changing environments and their effective strategies have been incorporated into their genome. Their cumulative reciprocal interaction can generate diverse and distinct lifespan controlling programs in ecotypes. Here, we aim to understand how lifespan controlling programs contribute micro-evolution or fitness of ecotypes in their surrounding environments.
- Investigation of association among phenomic responses, lifespan, and various environmental cues in various accessions through PHI (Plant High-throughput Investigator) system
– Identification of genetic elements and their natural alleles for lifespan controlling programs through genome-wide association study (GWAS)
– Dissection of molecular networks in accessions with distinct lifespan history
- Hyo Jung Kim, Sung Hyun Hong, You Wang Kim, Il Hwan Lee, Ji Hyung Jun, Bong-Kwan Phee, Timilsina Rupak, Hana Jeong, Yeonmi Lee, Byoung Seok Hong, Hong Gil Nam*, Hye Ryun Woo*, and Pyung Ok Lim*. Gene regulatory cascade of senescence-associated NAC transcription factors activated by ETHYLENE-INSENSITIVE2-mediated leaf senescence signalling in Arabidopsis. J Exp Bot 65(14), 4023-4036(2014).
- Rauf M, Arif M, Dortay H, Matallana-Ramírez LP, Waters MT, Gil Nam H, Lim PO, Mueller-Roeber B, Balazadeh S. ORE1 balances leaf senescence against maintenance by antagonizing G2-like-mediated transcription. EMBO Rep. 14(4):382-8 (2013).
- Hyunmo Choi, Suyeong Jeong, Dong Su Kim, Hyung Jin Na, Jong Sang Ryu, Seung Sik Lee, Hong Gil Nam, Pyung Ok Lim* and Hye Ryun Woo*. The homeodomain-leucine zipper ATHB23, a phytochrome B-interacting protein, is important for phytochrome B-mediated red light signaling. Physiologia Plantarum 150(2):308-320(2013)
- Hye Ryun Woo, Hyo Jung Kim, Hong Gil Nam, and Pyung Ok Lim. Plant leaf senescence and death – regulation by multiple layers of control and implications for aging in general. J Cell Sci 126(Pt 21), 4823-4833(2013).
- Kang HG, Kim J, Kim B, Jeong H, Choi SH, Kim EK, Lee HY, Lim PO. Overexpression of FTL1/DDF1, an AP2 transcription factor, enhances tolerance to cold, drought, and heat stresses in Arabidopsis thaliana. Plant Science 180(4):634-641 (2011).
- Woo HR, Kim JH, Kim JY, Kim JS, Lee U, Song IJ, Kim JH, Lee HY, Nam HG, Lim PO. The RAV1 transcription factor positively regulates leaf senescence in Arabidopsis. J Exp Bot. 61(14):3947-3957(2010).
- Lim PO, Lee IC, Kim J, Kim HJ, Ryu JS, Woo HR, Nam HG. Auxin response factor 2 (ARF2) plays a major role in regulating auxin-mediated leaf longevity. J Exp Bot. 61(5):1419-1430(2010).
- Kim JH, Woo HR, Kim J, Lim PO, Lee IC, Choi SH, Hwang D, Nam HG. Trifurcate feed-forward regulation of age-dependent cell death involving miR164 in Arabidopsis. Science. 323:1053-1057(2009).
- Lim PO, Kim Y, Breeze E, Koo JC, Woo HR, Ryu JS, Park DH, Beynon J, Tabrett A, Buchanan-Wollaston V, Nam HG. Overexpression of a chromatin architecture-controlling AT-hook protein extends leaf longevity and increases the post-harvest storage life of plants. Plant J. 52(6):1140-53(2007).
- Lim PO et al. Leaf senescence. Annu Rev Plant Biol. 58:115-36 (2007)
- Lim PO et al. Molecular genetics of leaf senescence in Arabidopsis. Trends in Plant Science 8:272-278 (2003)