We request partial support for a Federation of American Societies of Experimental Biology (FASEB) conference """"""""Lipid Modifications of Proteins"""""""", August 6-11, 2000 at Copper Mountain, CO, on structure and function of the three major classes of lipid modification; acylation, GPI-anchorage, and prenylation. This meeting relates to cancer because many lipid modified proteins (such as Ras and Src) are signaling proteins frequently mutated in human cancer. Lipid modification of these proteins is required for their transforming potential. Drugs that inhibit farnesylation of Ras can cause tumor regression in animal models and are in clinical trials. Bob Bishop of Schering Plough will speak on this topic. Membrane rafts (caveolae) are signaling centers that are important in both cancer and immunology. John Hancock will speak on how rafts affect signaling though H-Ras. Several reports show that T cell signaling occurs in rafts, as will be discussed by Marilyn Resh and Tony Magee. Another important focus of the meeting is on infectious disease. Lipid modification in pathogens such as Trypanosoma, Leishmania, and Plasmodium is crucial for pathogen survival, but has features not shared by mammalian hosts, and is an attractive target for pharmacological intervention. This avenue is being actively explored by Michael Ferguson (developing strategies for inhibiting GPI-anchorage in Trypanosoma brucei), by Jeffrey Gordon (looking at myristoylation in Candida albicans), by Fred Buckner (prenylation in Trypanosoma), and by Malcolm McConville (GPI-anchorage in Leishmania). In another strategy, Gisou van der Goot will discuss inhibition of intoxication by Aeromonas hydrophila toxin, which binds GPI-anchored proteins. The goal of this meeting can be summed up in the stated mission of NIGMS: it is """"""""aimed at improving the molecular-level understanding of fundamental biological processes and discovering approaches to their control."""""""" Most participants will come from academics, with others from industry and research institutes. The conference has previously been very successful in attracting women, junior, minority, and international investigators. In addition to the themes outlined above, the following topics will be covered: Biosynthesis, trafficking and function of GPI anchored proteins; Enzymology of lipid modifications; Role of cholesterol in signaling and membrane domains; Biology of CAAX processing; and Lipid modifications and protein targeting.
