KOSEN 한인과학기술자네트워크

1. Prokaryotic Transcription

    Multi-subunit RNA polymerase is one of the central enzymes related to the maintenance of life, synthesizing RNA transcripts from template DNA to produce proteins or regulate assorted cellular processes. Although RNA polymerase has been studied for the last five decades, its molecular mechanism is still to be elucidated due to its relatively large size and complicated structure. Prokaryotic RNA polymerases contain five subunits (two α, β, β’, and ω) and are highly conserved in all domains of life. It is advantageous to use bacterial RNA polymerases in mechanistic studies because they are relatively easy to prepare and their functions are simple to examine compared to the eukaryotic RNA polymerases. Therefore, we will study prokaryotic RNA polymerases using cryo-EM combined with assorted biochemical assays to understand the molecular mechanisms of transcription. The results from our study will deepen our understanding of certain fundamental principles in life and will provide the molecular basis for drug development efforts related to transcription processes.

2. Eukaryotic Transcription

    Eukaryotic transcription is much more complex than prokaryotic transcription and utilizes far more transcription factors and DNA elements for initiation and regulation compared to prokaryotic transcription. We are interested in the eukaryotic transcription as a fundamental mechanism of cell fate determination. The super-enhancer is a region on the genome that consists of a number of enhancers that bind to various protein factors, including RNA polymerase complexes. Failure of the formation of proper super-enhancer complexes can lead to the abnormal development of cells and cause various diseases, such as cancer. However, the formation processes of super-enhancer complexes are not well known, and the intrinsic heterogeneity and disordered structures of super-enhancer complexes will make the project more challenging. We will utilize the cryo-EM and biophysical methods to overcome these hurdles and reveal the structural architecture of the cell-fate-determining machinery.

3. Microbiome

    At the boundary between humans and the external environment, trillions of microbes, collectively referred to as the human microbiota, are widely present on the skin, respiratory trees, and in the gastrointestinal tract. The human microbiota affects humans either indirectly by producing a variety of molecules as metabolites or directly through contact with host cells. The microbiome is the term for the entire set of genes from the microbiota. The significance of the microbiome in various contexts of human life has been proven through the interdisciplinary efforts of experts in gnotobiology, genomics, cell biology, biochemistry, and analytical chemistry, but the chemical basis of how microbiota interact with the host through microbiome-derived metabolites remains obscure due to the lack of structural studies. We will investigate (1) how microbial metabolites are recognized by host receptors, and (2) how microbial metabolites are synthesized.