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THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. Memorandum To: Dr.J.F.Glenn and Staff From: D.H.Ford Re: Site visit with Dt. Richard Wright,Webb-Waring Lung Institute, Denver CO, October 10, 1990. Grant No.2603R1 entitled "Regulation of yeast Xanthine oxidase gene expression." Goals: To identify the gene encoding yeast xanthine dehydrogenase/ xanthine oxtdase, determine its base sequence and to study the regulation of the XO gene by oxygen, 027, H2O21 metals and various mutants constructed in vitro. Overview and Discussion:Following a brief introduction by Mrs. Z. Millerj the new Director for Webb-Waring, Dr. John Repine outlined some of the changes which have occurred recently. One of course was the transfer of Dr. Wright from the Boulder campus of the University of Colorado. A more major.addition has been the appoint- ment of Dr. Joe McCord from Alabama to direct a Molecular Biological component of the Institute. The current group of investigators appear to represent a more multidisciplinary group, but who all have a major interest in oxygen- and oxygen-mediated processes which under- lie many diseases.including those of the pulmonary, vascular, endo- crine and nervous systems as well as problems associated with cancer and arthritis. All members of the Institute are currently members of the University Health Science Faculty. As of now, while there may be other areas of research which may be considered at Webb-Waring, the principal focus and theme for research will be on the'good and bad' rol.s of oxygen and oxidants. Results:Dr.Wright presented an excellent overview of the free radical XD/XO situation in relation to disease.,which was most instructive. However, his own work, using the yeast model to obtain the gene encoding for this system appears to be moving rather slowly. While he has several preparations of yeast XD/XO activity, purification is progressing slowly. He has now obtained a cDNA encoding XD/XO from ab drosophila, which he believes will facilitate,,the full length XD protein in YE334 yeast cells after galactose induction. Fortunately, Dr. Wright has been able to discuss the use of a yeast model with Dr. Hagerman at the University Health Science Center, which should be of considerable help for him. Comments: Dr. Wright is a young and apparently very bright investigator who is only a few years beyond his post-doctoral work. He is enthus- iastic and knowledgable, but will no doubt benefit from his associa- tion with such Senior investigators as Dr. McCord. Thus, while his project appears to be off to what might be considered a slow start, I have no doubt that it will improve with time. Further, since his support from CTR only commenced 9 months ago, one can not expect him to have already completed his three-year study. It will certainly be interesting to follow this young man's investigation5and see how they mature with time. DHF