Kouichi Iwasaki, PhD Assistant Professor Molecular Pharmacology and Biological Chemistry Molecular biology and genetics of a rhythmic behavior Curricula: Neurobiology Molecular Biology and Genetics E-mail:   k-iwasaki@northwestern.edu

Biological rhythms are intrinsic activities and are widely observed from single-cell organisms to higher vertebrates. These rhythms are thought to be part of an essential evolutionary adaptation. For example, the ~24-hour circadian rhythm is found in various organisms including humans, and emerged as an adaptation to the 24-hour day/night cycle. The range of biological rhythms is wide — from milliseconds through years — and includes repetitive firing of neurons (milliseconds), heartbeats (a second), breathing (seconds), internal organ peristalsis (minutes to hours), sleep cycles (hours), and ovulation cycles (weeks). Since these rhythms are intrinsic to our body physiology, it is extremely important to understand their mechanisms for medical reasons as well as for basic scientific issues.

The ultimate goal of my research is to understand the molecular and cellular mechanism of one biological rhythm, the defecation rhythm, using a model organism the nematode C. elegans. In the C. elegans experimental system, powerful genetic and molecular biological approaches are available. In particular, forward genetics has the potential to unveil new genes for various biological processes, even after the entire genome sequence is known and whole-genome assays, such as DNA microarrays, are available. Using forward genetics, new genes for various biological processes can be identified, as forward genetics relies solely on biologically relevant mutant phenotypes and not on other information such as biochemical activities and gene-expression patterns. Also, gene disruption has been very successful in the C. elegans system, for example, through the use of RNA interference (RNAi). Therefore, the feasibility of both forward and reverse genetics is a great advantage in this model system.

In the C. elegans system, physiology is generally less advanced compared to other model systems. However, my lab was the first in the world to develop calcium-imaging, tissue-culture, and electrophysiological techniques specialized to the C. elegans intestine. By combining our new physiological techniques with genetic, molecular, and genomic approaches, we should be able to strongly contribute to unveiling the regulatory mechanism of the defecation rhythm and deepening our knowledge about biological rhythm physiology in general.

Publications:

Doi, M. and Iwasaki, K. (2002) Regulation of retrograde signaling at neuromuscular junctions by the novel C2 domain protein AEX-1. Neuron. 33, 249-259

Iwasaki, K. and Toyonaga. R. (2000) The Rab3 GDP/GTP exchange factor homolog AEX-3 has a dual function in synaptic transmission. The EMBO Journal. 19, 4806-4816

Iwasaki, K. Staunton, J. Saifee, O. Nonet, M. and Thomas J. H. (1997) aex-3 encodes a novel gene product that regulates presynaptic activity in C. elegans. Neuron 18, 613-622

Iwasaki, K. and Thomas J. H. Rhythm in Genetics. (1997) Trends in Genetics. 13, 111-115.

Iwasaki, K. Liu, D. W. C. and Thomas J. H. (1995) Genes that control a temperature-compensated ultradian clock in Caenorhabditis elegans. Proc Natl Acad Sci USA. 92, 10317-10321.