| Citation | S. Numa is regarded by many as the most distinguished molecular biologist now working in Japan. Apart from periods at the Harvard Medical School Department of Biological Chemistry and the Max-Planck-Institut at Munich, he has been throughout his career on the academic staff of the Kyoto University Faculty of Medicine. In Germany he made important contributions on acetyl-coenzyme-A functions, which he developed extensively in a series of studies in Japan. This work led him to studies of the regulation of such function at the level of messenger RNA. Subsequently he initiated molecular genetic studies of the protein precursors of neuropeptides, a new field of which he was a pioneer. He identified such a precursor for corticotropin (ACTH), and subsequently cloned the cDNA for this precursor protein, termed pro-opiomelanocortin, and thus determined its full amino acid sequence. This was a major breakthrough for the whole field of neuropeptides, opening new vistas. He and his co-workers went on to clone and sequence the precursor protein of the enkephalins, pre-proenkephalin. Yet another precursor protein, that for dynorphin and alpha-neo-endorphin, was then similarly elucidated by his group. His laboratory further identified and sequenced by recombinant DNA techniques the precursor of the corticotropin-releasing factor (CRF) hormone. He went on to establish the DNA sequences of the full genes, with their introns, for pro-opiomelanocortin, for pre-proenkephalin and for the CRF precursor. Our concepts of the origin and control of whole families of neuropeptides have been clarified by the fundamental discoveries thus made. Professor Numa has more recently turned his attention to the molecular biology of receptor proteins. For the nicotinic acetylcholine receptor, he was one of the first to apply successfully the powerful methods of molecular genetics, and his group achieved the astonishing feat of cloning and sequencing all the cDNAs for the receptor structure (from the electric organ), representing four genes, resulting in the determination for the first time of the primary structure of an entire receptor protein. From this, that laboratory has gone on to report the DNA and full protein sequences derived from genes encoding muscle acetylcholine receptor polypeptides, including, as a further tour-de-force, analysis at the genomic level for human muscle. His contribution on the acetylcholine receptor could reasonably be claimed to be the most illuminating of any laboratory on it to date. In each of the above-mentioned studies, Profesor Numa has followed investigations in depth. Thus, he examined and interpreted the distribution of introns and exons in each of the above-described families of genes, he compared the same gene in different species and its mRNA in different tissues, and he analysed flanking DNA sequences, and their determination of gene transcription. The extraordinary productivity of his laboratory is combined with high accuracy and rigorous standards of evidence. Neurobiologists and molecular biologists generally regard his achievements as truly outstanding, and they are proving in practice to be an inspiration to other laboratories. Thus, Professor Numa's work has been recognised in the award of 3 Japanese and 3 international prizes. |