Laboratory of Chemical Biology for Drug Discovery
Graduate School of Pharmaceutical Sciences
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-033, Japan
TEL & FAX +81-3-5841-4775 (office room)
Staff:
Toichi TAKENAKA, Ph.D., Professor
(pharmacology and drug discovery)
Takao ISOGAI, Ph.D., Professor,
(genome science, molecular biology, chemical biology and genetics)
Ai WAKAMATSU, Assistant Professor
(genome science and molecular biology)
Research field:
Studies on chemical biology for drug discovery based on genome sciences
Research Subjects:
The laboratory of Chemical Biology for Drug Discovery was established on
April 1, 2007 with an endowment from Astellas Pharm Inc. for establishing
a new concept and basis in a medicinal science by coordinating research
with Graduate School of Pharmaceutical Sciences, The University of Tokyo
and other academic institutions. In the laboratory, both research technologies,
chemical biology and genome science, are used for a new drug target discovery
research described below.
1. Medicinal science study using small molecule compound-immobilized new
affinity resin method developed by our previous NEDO project for the drug
target protein analysis.
2. Medicinal science study focusing on human mRNA variations related to
diseases and cell differentiation by splicing and transcription start sites
for the drug target search and evaluation using FLJ human full-length cDNAs
and the constructed cDNA database, and expression profiling data from human
culture cells and tissues.
3. Research target diseases: cancer, neural disease and autoimmune disease.
Research Topics:
1. FLJ Human cDNA Database focused on mRNA variations
Human gene number was estimated to be 20 - 25 thousand. However number
of human mRNA varieties was predicted to be about 100 thousand. The varieties
are caused by variations of transcription start site (TSS) and splicing.
We developed efficient human splicing variant cDNA cloning and evaluation
systems, and then obtained more than one thousand of full-length sequenced
cDNAs. In addition we constructed the sequence analysis database focused
on mRNA variations using human genome and cDNA sequences, FLJ Human cDNA
Database (http://flj.hinv.jp/, http://flj.lifesciencedb.jp).
For construction of FLJ Human cDNA Database focused on mRNA variations, about 1.4 million of our 5'-ESTs of full-length cDNAs by oligo-capping method, 20,979 of isolated and sequenced FLJ full-length human cDNAs, 82,452 of full-length sequenced human cDNAs (30,326 cDNAs of our FLJ project and 52,126 cDNAs of KIAA, MGC, DKFZ and other institutions), 29,761 of human RefSeq, 47,585 of human Ensembl gene transcripts, about 110 thousand of our 3'-ESTs and about 4.3 million of ESTs from UniGene except our ESTs were mapped to human genome sequence. Clustering of cDNA sequences were done based on the mapping results.
In our human cDNA project, we obtained about 30 thousand of FLJ human full-length sequenced cDNAs and about 1.4 million of 5'-ESTs of FLJ full-length cDNAs from about 100 kinds of cDNA libraries consist of human tissues and cells constructed by oligo-capping method. The majority of the insert cDNA sizes was over 2 kb and the average full-length rate of 5'-ends of cDNAs was 90%. And our FLJ cDNAs were covered about 80% of human genes. Then we developed efficient human splicing variant cDNA cloning and evaluation systems. About 21 thousand of finished grades of full-length sequenced cDNAs were newly obtained and about 12 thousand of those were isolated as splicing variant cDNAs. In addition we constructed the sequence analysis database focused on mRNA variations using human genome and cDNA sequences. After those sequences were mapped onto the human genome sequences, clustering of the cDNA sequences were done based on the mapping results. Functional annotations described below were done. (1) cDNA cluster information: a) mRNA variation viewer. In this viewer variations of ORFs, domains and motifs are able to be viewed and expression profiles by our 5’-ESTs of high full-length rate cDNAs are also shown. b) annotation 1, genome positions and locus information of cDNA clusters; (2) cDNA information: a) annotation 2, genome locus information of cDNA sequences; b) annotation 3, functional annotations of cDNA sequences and the translated amino acid sequences such as BLAST analysis results, Pfam, SignalP, SOSUI, GO (Gene Ontology) and so on. Annotations described above are able to be searched and viewed in FLJ human cDNA database. Constructed FLJ human cDNA database will be useful for selection and evaluation of human mRNA variations by TSS and splicing.
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