Tobacco Documents Online

Tui: COU:vCIL FOR TOBACCO RESEARCH--U.S.A., INC. MEMORANDCmf TO: W. U. Gardner and Staff FROM: D. H. Ford and D. Stone March 27, 1979 SUBJECT: Grant 1126R1 and Application 1126-A. Linda *1. Hall, Ph.D., Mass. Inst. of Technolo gy, Cambridge, Mass. "Genetic Differences in Nicotine Sensitivity in Drosophila MelanoLaster Strains." Site Visit on March 21; 1679. We discussed with Dr. Hall the nature of her future plans, as there is a high probability of her moving to the Genetic Unit at the Albert Einstein Medical Center next fall. She would of course plan to continue her work with Drosophila nicotine mutants, of which perhaps 20 of the mutant substrains from the 114 she has obtained appear sufficiently promising to pursue in determining what the mutational effect is on the nACh receptor. Receptor protein from a substrain she has called HR appears to be located on the X chromosome near the site for the gene which determines that a fly wing will be cross veinless. She is current3y looking for light and temperature sensitive variants in relation to nicotine resistance. She has purified the receptor to homogeneity in the wild type and in some of the mutants. With the wild type she knows the molecular subunits for the CNS nACh recep_or. With 8 of the N-resistant mutants, the receptor migrates vrith isoelectrie focusing like that of wild type fiies, while with 4 others there is a shift in the isoelectric iocusing from an isoelectric point of 6.6 (6.7 in the HR strain on which most has been done). When HR and wild type fly receptors are mixed, two peaks emerge for the twQ isoelectric points. There still remain receptor protein from the 8 additional mutant strains to analyze. When the receptor protein from mutant flies is run through an affinity column, part of the protein binds to the labeled 1251 bungarotoxin on the column and part passes through, suggesting two classes of receptor. Hopes to have receptor proteins characterize d as to isoelectric focusing for the 20 more promising strains. Then plans to establish hybrids of these substrains and determine effects on hybrids. Dr. Hall's expected move to Einstein will probably be accomplished by September. She is delaying final contract signing until the University gets her laboratory quarters establishe d so that she can move in and get directly to work. From what she says, this has required extensive building alterations. She will be taking much cf her equipment with her to Einstein, but will be unable to take a UV-vis spectrometer or a liquid .scintillation spectrometer with her from MIT, as the ones she has been using belong to her Department at MIT. Apparently the authorities at Einstein may not provide these instruments for her. The techniques which she uses require boih these instruments, and it would bc difficult for hPr to continue without replacing them. (It might be further noted that the ones she is leaving at MIT are both very old and probably in need of replacement.) It should be pointed out that Dr. Hall has requested funds for this equipment in the over . .

. ~ CTR budget applicati,3n. However, if the Einstein Medical School does provide the instruments, then the CTR budget can be adjusted. Dr. Habl is an active person who is doing exciting work in biochemical genetics, in particular in relation to how genetic mutation might alter the biochemical charac*eristic of,the nACh receptor to the extent at least in the fruit fly that it becomes resistant to nicotine (normally lethal to flies and other insects). As she expands on her information of the characterization of the nACh receptor in normal and mutant n-resistant flies, it might be interesting to determine what ESR would reveal in the mutant receptor as compared with the normal wild type. D. H. Ford P. Stone /ek I