TSUKAHARA Laboratory
<Major Research Areas>Molecular biology, biotechnology

Understanding and Application of Life Phenomena through Integration of Nanotechnology and Biotechnology

Research activity

　　All living organisms on the earth, including human beings, have “genes”, which are basically composed of the same compounds across all the species. Genes are the design drawings of protein structures, and they determine when and where protein should be produced, and what kind of protein it should be. For example, although cells and organs such as skin, muscle, brain and liver have the same genome consisting of the same suite of genes, each of their cells produce different kinds of protein and have different shapes and functions. Thus, the information in genes includes orders of the time and place to read their information and generate mRNA for each protein.
　　By the way, you’ve probably heard the word “predisposition”. The word includes the diatheses of being susceptible to certain diseases and/or the effectiveness of certain medicine. Predispositions are also thought to be determined by small and personal variations in genome. We are developing DNA chips to analyze the expression levels of genes and genetic variations exhaustively. We are also investigating life phenomena using these devices. We believe that understanding these life phenomena will lead to the discovery of treatments for diseases.
　　The phenomenon of splicing is observed in living organisms, yeast or higher eukaryotes. In a genomic gene, there exists a part called “exon”, which is retained in, and “intron”, which is excluded from mRNA. During the splicing process, only exons will be joined together to generate mRNA, the design drawing of protein. We are also investigating the control mechanism of splicing, and analyzing the functions of neural-specific splicing factors. In addition, we investigate the genes that influence cellular differentiation (especially toward nerves and cardiac muscle) and conduct fundamental research on medical treatment methods.
　　 Biological molecules such as nucleic acids and proteins have the ability to construct a huge architecture through selforganization in spite of their nano-scale sizes. They are also excellent nano-materials that have the particular functions of molecular recognition ability, catalytic activity, etc. The designs of the biological molecules of these nano-materials are also drawn by genes, which are biological molecules as well. Our laboratory aims to clarify life phenomena based on molecular biology and establish new uses for bio-materials such as genes, proteins and cells.

Equipment

ABS 3130xl Genetic Analyzer (DNA sequencer), ABS GeneAmp PCR system, Stratagene Mx3000P (Multi specimens real-time PCR), Fujifilm LAS3000 multicolor (Fluorescent image analyzer), HitachiSoft CRBIO-IIe (Microarray scanner), Agilent 2100 Bioanalyzer TECAN XFLUOR4 (Multi-plate reader), Cell culture equipment including a safety cabinet and CO2 incubator

The main research achievements in the past five years

1. H. Suzuki, K. Osaki, K. Sano , A.H.M.K. Alam, Y. N akamura, Y. Ishigaki, K. Kawahara, and T. Tsukahara: Comprehensive Analysis of Alternative Splicing and Functionality in Neuronal Differentiation of P19 cells. PLoS ONE. in press.
2. A.H.M.K. Alam, H. Suzuki, T. Tsukahara: Retinoic acid treatment and cell aggregation independently regulates alternative splicing in P19 cells during neural differentiation. Cell Biology International,34, 631-343 (2010).
3. N.-H. Ab Hakim, T. Kounishi, A.H.M.K, Alam, T. Tsukahara, H. Suzuki: Alternative splicing of Mef2c promoted by Fox-1 during neural differentiation in P19 cells. Genes Cells, 15, 255-267 (2010).
4. A. Ohkubo, R. Kasuya, K. Sakamoto, K. Miyata, H. Taguchi, H. Nagasawa, T. Tsukahara, T. Watanobe, Y. Maki, K. Seio, and M. Sekine,'Protected DNA Probes'capable of strong hybridization without removal of base protecting groups, Nucleic Acids Res., 36, 1952-1964 (2008).
5. S. Uchida, S. Fuke and T. Tsukahara: Up-Regulations of Gata4 and Oxytocin Receptor are Important in Cardiomyocyte Differentiation Processes of P19CL6 Cells. J.Cellular Biochem. ,100, 629-641 (2007).