96-00587 Johansen The organization of the nucleus is exceedingly complex and is intricately interrelated with gene expression, cell differentiation, and cell division. During each cell cycle, the chromosomes must be faithfully replicated, the complex nuclear matrix must be duplicated and reorganized, and microtubule assembly must be coordinated. Studying nuclear reorganization events that occur during mitosis should provide significance insights into cell cycle control and into the role of nuclear organization in nuclear functions. Therefore, it is important that as yet unknown components of the nuclear structure be identified as well as the regulatory molecules involved in the process of reorganization. A monoclonal antibody, mAb2A, has been isolated and has been shown to label Drosophila nuclei in a cell cycle-specific pattern: The antibody recognizes a nuclear meshwork at interphase, a spindle-like structure during prophase, and the mitotic spindle at metaphase. This antibody recognizes a novel nuclear protein, JIL-1, that contains two ser-thr-like catalytic domains bounded by a moderate (15 KD) C-terminus and a large (90KD) N-terminal domain. This tandem kinase domain coupled with its cell-cycle specific localization pattern in the nucleus suggests that JIL-1 may be involved in signal transduction events regulating and/or responding to mitotic events. The identifications of mutants in JIL-1 in combination with perturbation studies with molecular and biochemical analysis will hopefully provide insights into the function of JIL-1 and possibly identify the signal transduction pathway(s) in which it operates. The educational component of the CAREER proposal employs two broad approaches: First, a more formalized development of courses that target larger groups of students and are designed to improve accessibility and understanding of genetics to major in the life sciences; Second, a very individualized approach counseling students in planning their careers and personally working with them on independent research projects. %%% The organization of the nucleus is exceedingly complex and is intricately interrelated with gene expression, cell differentiation, and cell division. During each cell cycle, the chromosomes must be faithfully replicated, the complex nuclear matrix must be duplicated and reorganized, and microtubule assembly must be coordinated. Studying nuclear reorganization events that occur during mitosis should provide significance insights into cell cycle control and into the role of nuclear organization in nuclear functions. Therefore, it is important that as yet unknown components of the nuclear structure be identified as well as the regulatory molecules involved in the process of reorganization. The educational component of this CAREER proposal employs two broad approaches: First, a more formalized development of courses that target larger groups of students and are designed to improve accessibility and understanding of genetics to major in the life sciences; Second, a very individualized approach counseling students in planning their careers and personally working with them on independent research projects. ***