In multicellular organisms, the majority of cells possess identical DNA sequences. However, within a single organism, there exist diverse cell types exhibiting variations in morphology, function, and gene expression patterns. These biological observations underscore the significance of regulatory processes that extend beyond the DNA sequence, collectively referred to as epigenetic regulation. Epigenetic regulatory mechanisms, encompassing chromatin modifications, chromatin structure, RNA modifications, and more, play vital roles in nearly all biological processes within eukaryotes.

The Lu Laboratory at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, is dedicated to investigating the epigenetic mechanisms that govern cell fate programming and reprogramming. The research in the laboratory primarily centers around mammalian early embryos and stem cells as key model systems. The laboratory primarily focuses on three main directions of study:

1. Mechanisms of Epigenetic Regulation

This research direction focuses on investigating the mechanisms of chromatin-based epigenetic regulation as well as RNA epigenetic regulation mediated by the poly(A) tail. We are actively engaged in exploring novel carriers of epigenetic information and understanding the mechanisms involved in writing, reading, and erasing this information. Notably, we have recently discovered the presence of widespread non-A residues within the body of RNA poly(A) tails. The number, type, position, and combinations of these non-A residues within poly(A) tails, along with the poly(A) tail length, may encode extensive epigenetic regulatory information, which may represent potentially represents an entirely novel layer of gene expression regulation that has been previously overlooked. In essence, our primary focus lies in deciphering regulatory information that is not encoded by the DNA sequence.

2. Epigenetic Regulation underlying Mammalian Development

Our research aims to unravel the intricate epigenetic regulations that govern mammalian development. To gain insights into the programming and reprogramming of cell fate during development, we primarily utilize mammalian early embryos as a model system. The early embryos offer a unique perspective as they undergo profound cell fate changes from the single-cell zygote stage onwards. By comprehending the underlying regulatory mechanisms, we strive to develop innovative strategies for various applications. These include advancing mammalian reproduction techniques, establishing pluripotent/totipotent stem cells, and achieving somatic cell reprogramming. Additionally, we employ tissue/cell regeneration as an additional model to explore the epigenetic mechanisms regulating tissue development, aiming to develop strategies for promoting tissue/cell regeneration for therapeutic purposes.

3. Application of Poly(A) Tail Epigenetic Information in mRNA-based Biotechnology

In our preliminary study, we have made a compelling discovery that non-A modifications present within the poly(A) tail of mRNA can substantially enhance mRNA translation. This finding, coupled with our proprietary technology (patent pending), holds immense potential in mRNA-based biotechnology. Our ongoing research aims to unravel the regulatory mechanisms underlying these non-A modifications within mRNA poly(A) tails, which contribute to the improved efficiency of mRNA translation. Furthermore, we intend to leverage this knowledge to develop a suite of innovative poly(A) tail-based technologies specifically tailored for the design of mRNA vaccines and therapeutics.

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