RUI: m-Survivin Expression in Differentiating Lymphocytes

Haverford College, Haverford PA

Investigators

Abstract

Apoptosis, or programmed cell death, is utilized extensively in the functioning immune system. During development, cells which express potentially auto-immune or functionally irrelevant receptors are excised before they reach maturity. In addition, once a lymphocyte has participated in an antigen-specific response, it may be eliminated either passively, following growth factor withdrawal, or actively, after interaction with cells bearing death-inducing signals. In this project, the role of the IAP (Inhibitors of APoptosis) family of anti-apoptotic proteins will be explored in normal lymphocytes. IAPs share a unique, 70 amino acid BIR (Baculovirus Inhibitor of apoptosis Repeat) domain and most function by inhibiting some of the caspase enzymes which play a central role in apoptosis. Mouse- (m)-survivin, the central focus of this work, is the smallest and simplest of these interesting IAP proteins. The thesis to be investigated is that different anti-apoptotic molecules may function at particular stages in the lymphocyte life-cycle. In particular, it is posited that survivin acts to preserve lymphocyte viability in cells which are undergoing rapid proliferation and/or are subject to active selective pressure. The signals and conditions which induce m-survivin expression in B and T lymphocytes, both in vivo and in vitro will be investigated and the relative kinetics of IAP expression will be compared with those of other anti-apoptotic proteins. The lymphocyte subpopulations in which m-survivin is expressed will be defined, and the experiments will also explore the effects of over-expression of survivin on the capacity of lymphocytes to withstand induction of cell death. Finally, a novel modification of mRNA differential display methodology, first developed by the PI's laboratory will be employed to characterize the expression of multiple members of the BIR-containing family in differentiating lymphocytes. This research will be conducted at an undergraduate institution. The primary participants will be senior year and summer research undergraduates in the PI's laboratory at Haverford College. Significant contributions to the work are expected from undergraduate students who are members of under-represented groups. Students are involved at every stage of the research, from selection of their individual projects to presentation of the work, either at local or national meetings or in final written form. The control of apoptosis is a burgeoning field of research with major implications for the regulation of cellular proliferation across the eukaryotic kingdom.