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'''Research Summary'''
'''Research Summary'''


Our research focuses on functional genomics of tRNA, RNA epigenetics and RNA folding.
Our research focuses on (i) functional genomics and biology of tRNA including microbiomes and (ii) epitranscriptomics including microbiome-host interactions.


Translational regulation is related to the dynamic properties of tRNA that constantly change to facilitate stress response and adaptation to new environments and to control gene expression. We developed microarray methods that measure tRNA abundance, fraction of aminoacylation and misacylation at the genomic scale. We are exploring roles of tRNA in translational control in mammalian cells.
'''tRNA biology:''' Translational regulation relies on the dynamic properties of tRNA that constantly change to facilitate response and adaptation to new environments and to control gene expression. We developed high throughput sequencing technologies that measure tRNA abundance, charging and modifications in one single sequencing library. We are investigating the roles of tRNA in translational control and extra-translational functions in mammalian cells.
'''Microbiome:''' We also developed tRNA-seq as another approach for microbiome characterization. Standard microbiome characterizations include 16S-seq or shotgun metagenomics. Although powerful, these DNA-based methods do not directly report the microbiome activity such as dynamic gene expression which requires the studies of RNA in the microbiome. Our microbiome tRNA-seq results show extensive variations of tRNA abundance and modification patterns in microbiomes from different sources. We also show that tRNA modification dynamics in the microbiome correlates with tuning the expression of specific microbial proteins, indicating that tRNA-seq can provide new insights in microbiome biology. We are further developing this approach to explore the potentials of tRNA-seq to study microbiomes from humans and from the oceans.


A central tenet of biology is the accurate flow of information from nucleic acids to proteins through the genetic code. It is commonly believed that translation deviating from the genetic code is avoided at all times. We discovered that mammalian cells can deliberately reprogram the genetic code through tRNA misacylation upon innate immune activation and chemically triggered oxidative stress. The reprogramming is regulated by fluctuating levels of reactive oxygen species (ROS) in the cell. We are investigating how regulated mis-translation is used as a mechanism for stress response.
'''Epitranscriptomics:''' Over 100 types of post-transcriptional RNA modifications have been identified in thousands of sites in the transcriptome. They include methylation of bases and the ribose backbone, rotation and reduction of uridine, base deamination, addition of ring structures and carbohydrate moieties, and so on. mRNA modifications are involved in cell differentiation, proliferation, and many other cellular functions and human diseases. Some mRNA modifications can also be removed by cellular enzymes, resulting in the dynamic regulation of their functions. We are investigating the function and mechanisms of mRNA modifications such as N6-methyladenosine (m6A) in the regulation of gene expression. For example, we discovered that m6A modification can alter the local mRNA structure to regulate binding of mRNA binding proteins transcriptome-wide (m6A switch), resulting in changes in mRNA abundance and alternative splicing.  


Over 100 types of post-transcriptional RNA modifications have been identified in thousands of sites from bacteria to humans. They include methylation of bases and the ribose backbone, rotation and reduction of uridine, base deamination, addition of ring structures and carbohydrate moieties, and so on. RNA modifications are involved in stress response, environmental adaptation, and antibiotic resistance. Some modifications can be removed by cellular enzymes, leading to dynamic regulation of their function. We are investigating the function of RNA modifications in cell growth, adaptation and development.
'''Microbiome-host interactions through epitranscriptomics:''' We are working on elucidating the function of mammalian host mRNA and tRNA modifications in response to the gut microbiome. We found that microbiome reprograms the host m6A modifications transcriptome-wide in a tissue-dependent manner, suggesting that this dynamic epitranscriptomic mark is used in yet unknown ways in microbiome response. We also found that a microbiome dependent, host tRNA modification alters the cellular small RNA pool, suggesting yet another pathway of microbiome response through RNA modifications.


We are also investigating how RNA folds during transcription to understand RNA folding and structural rearrangement in the cell.


<font color=#000000 size=2> [[Pan Lab |Main]] | [[Pan:What we do|What we do]] | [[Pan:Who we are|Who we are]] | [[Pan:Research positions|Research positions]] | [[Pan:Press|Press]] |  [[Pan:Publications|Publications]] | [[Pan:Protocols|Protocols]] | [[Pan:Links|Links]] | [[Pan:Contact us|Contact us]]
 
<font color=#000000 size=2> [[Pan Lab |Main]] | [[Pan:What we do|What we do]] | [[Pan:Who we are|Who we are]] | [[Pan:Press|Press]] |  [[Pan:Publications|Publications]] | [[Pan:Methods|Methods]] | [[Pan:Links|Links]] | [[Pan:Contact us|Contact us]]

Latest revision as of 12:47, 26 December 2018

Research Summary

Our research focuses on (i) functional genomics and biology of tRNA including microbiomes and (ii) epitranscriptomics including microbiome-host interactions.

tRNA biology: Translational regulation relies on the dynamic properties of tRNA that constantly change to facilitate response and adaptation to new environments and to control gene expression. We developed high throughput sequencing technologies that measure tRNA abundance, charging and modifications in one single sequencing library. We are investigating the roles of tRNA in translational control and extra-translational functions in mammalian cells.

Microbiome: We also developed tRNA-seq as another approach for microbiome characterization. Standard microbiome characterizations include 16S-seq or shotgun metagenomics. Although powerful, these DNA-based methods do not directly report the microbiome activity such as dynamic gene expression which requires the studies of RNA in the microbiome. Our microbiome tRNA-seq results show extensive variations of tRNA abundance and modification patterns in microbiomes from different sources. We also show that tRNA modification dynamics in the microbiome correlates with tuning the expression of specific microbial proteins, indicating that tRNA-seq can provide new insights in microbiome biology. We are further developing this approach to explore the potentials of tRNA-seq to study microbiomes from humans and from the oceans.

Epitranscriptomics: Over 100 types of post-transcriptional RNA modifications have been identified in thousands of sites in the transcriptome. They include methylation of bases and the ribose backbone, rotation and reduction of uridine, base deamination, addition of ring structures and carbohydrate moieties, and so on. mRNA modifications are involved in cell differentiation, proliferation, and many other cellular functions and human diseases. Some mRNA modifications can also be removed by cellular enzymes, resulting in the dynamic regulation of their functions. We are investigating the function and mechanisms of mRNA modifications such as N6-methyladenosine (m6A) in the regulation of gene expression. For example, we discovered that m6A modification can alter the local mRNA structure to regulate binding of mRNA binding proteins transcriptome-wide (m6A switch), resulting in changes in mRNA abundance and alternative splicing.

Microbiome-host interactions through epitranscriptomics: We are working on elucidating the function of mammalian host mRNA and tRNA modifications in response to the gut microbiome. We found that microbiome reprograms the host m6A modifications transcriptome-wide in a tissue-dependent manner, suggesting that this dynamic epitranscriptomic mark is used in yet unknown ways in microbiome response. We also found that a microbiome dependent, host tRNA modification alters the cellular small RNA pool, suggesting yet another pathway of microbiome response through RNA modifications.


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