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Council for Tobacco Research

"Site Visit with Dr. Linda Hall [Gr01126b]

Date: ALBERT EINSTEIN COLLEGE OF MEDIC
Length: pages
HK1160016-HK1160017
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Abstract

SOMMERS SC;STAFF

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Type
BRONX
Author
New York
Named Person
Hk1160016-0017
Depository Date
Memorandum
Master ID
19960515

Related Documents:
Litigation
Reports on Site Visit to Assess Research Progress
Recipient
June, 1.0.
Copied
1982. Grant, N.O. 1126b Entitled "Genetic Differences, I.N. Nicotine Sensitivity, I.N. Drosophilia Melangaster Strains.""
Site
131
Box
19820610
Request
Ford
Dh
Brand
159
E
UCSF Legacy ID
nqf20a00

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Page 1: nqf20a00
Memorandum Tot Dr. S.C. Sommers and Staff From; D.H. Ford H K~1 1 60C16 Re., Site visit with Dr. Linc'a Hall, Albert Einstein College of Medicine, Bronx, New York,. June 10, 1982. Grant No. 1126B entitled "Genetic Differences in Nicotine Sensitivity in Drosophila melanogaster Strains." Despite a busy summer last year at Woodshole and a heavy te iching ]program, work on the isolation and purification of the ACh receptor of the fruit fly has continued to progress. A manuscript on this work was submitted to JBC and accepted, subject to some revision and additions of ad ditional data. Thus, much of the time since my last visit has been devoted to p'erforming additional experiments on the purification of the receptor protein and determination of its molecular size, confirming the work presented in the original manuscript. A mod ified up-to-date copy of the rewritten manuscript will be submitted to CTR within a few weeks, as well as a manuscript on a newly completed study. A large number of gels of separated receptor proteins are waiting in the freezer (based on new work) and will be processed this summer. On of the graduate students from Dr. Ne lson's group was down for about a month earlier this year learning the method of receptor preparation. Dr. Hall feels that he should be able to perform this quite well. Expects to be starting work on some new mutants involving ACh esterase obtained from Dr. W. Gelbart at Harvard. These flies have changed phenotypes but have presumably unchanged esterases. A Miss Charlene Comastri will be working with these mutanta this summer, doing binding studies in relation to sensitivity of the different mutants to nicotine. Another area being investigated is the development of a new pro'cedure for separating cell membrane fragments on a discontinuous ficbl gradient. These membrane separations will enable her to obtain pure vesicle fractions (verified by EM) which can then be used to develop a fbnctional assay for the ACh receptors. DF. Hall has also developed a contact wi th a Dr. H. Bteer at Osnabruck, Germany who will be doing EM studies to determine if there are synaptic specializations in the mutant flies vs. the wild type. Feels this information would also be useful in interpretting the data which Dr. Nelson will be obtaining on the receptors by NMR techniques.
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-2- NKQ1?600i7 Dr. Ha2l is also now considering an immunological approach wherein one might be able to assay separately for each of the 4 peptides which make up the ACh receptor, using monoclonal anti- bodies. Such an approach would permit her to determine more easily which of the 4 peptides changes in the mutant flies. Apparently such monoclonal antibodies may be obtainable from the investigators who have already worked on generating antibodies to Drosophila proteins. Dr. Hall would then simply use the monoclonals as tools to further her assays of changes in the peptides which characterize the ACh receptor. Comment: While work this past year has been somewhat slowed by the necessity to expand the data base for an accepted manuscript (completed) and by a relatively heavy teaching load, the study should proceed more rapidly during the ensuing year since Dr. Hall will have a much lightened teaching load and only plans to spend a half summer at the Woodshole laboratory this year. Her plans for the coming year with the co-worker in Germany and with the use of monoclonals to assay for change in receptor protein in the mutant flies (in conjunction with the NMR studies with Nelson) should produce some interesting information about the nicotine response in the morphology and chemistry of the fruit fly ACh receptor. Merits continued support. D.H. Ford

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