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THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. 900 THIRD AVENUE NEW YORK. N. Y. 10022 Mem or andum To: Dr. H. McAllister and Staff From: D.H.Ford Re: Site visit with Dr. William Petri, University of Virginia at Ch ar lottesville, VA, Oct. 13, 1993. Grant No. 3594 entitled "Mechanism of Entamoeba histolytica resistance to human compliment C5b9" Goals: 1.Determine how anti-adhesin antibodies potentiate lysis of Entamoeba histolytica by C5b-9. 2. Determine how galactose-specific adhesin inhibits assembly of the C5b-9 pore. and 3. Determine the mechanism of expression of C5b-9 resistance in Entamoeba histolytica. Progress: Inasmuch as this CTR supported program was only initiated July 1, 1993, there is 7iittZe oz:no progress which can be attributed to CTR support. In view of this, I was fortunate to be able to attend a seminar in which this program was discussed. Dr. Petri initiated discussion with an overview of the problem wherein this protozoan parasite infects a half billion people annually and is a major cause of parasitic death. Unfortunately, these parasites resist killing by the C5b-9 membrane attack complex of ccxnplement that is deposited on the amebic cell membrane. This resistance can be overcane by an mAb to the galactose adhesin., suggesting that the adhesin on the cell membrane of the parasite protects it. Details of the specific components of this program were then discussed by 5 of Dr. Petri's graduate students, details of which are presented in his grant proposal. 1. How and at what step does mAb 3D12 block the effect of C5b-9 on adhesin?. Preliminary data indicated that the effect of the anti- body occurred after binding tda the cecl l. surface. 2. The region of adhesin recognized by the antibody is in a 170kDa subunit rich in cysteine. Preliminary results were presented for all the projects listed under experimental designs and procedures for groups 1 and 2. It appears from the presentations by these students and one post doc that Dr. Petri has allocated a separate phase of the overall program to each student and then coordinates their individual efforts. All-in- all, it was an interesting series of presentations in which the students appeared knowledgable with the the various techniques required for their individual components as well as being familiar with what the others were undertaking.With this active and enthusiastic team I would be surprised if excellent progress was not accomplished. DHF