Shelley Sazer, Ph.D.
Department of Biochemistry and Molecular Biology
Department of Molecular and Cellular Biology
Education and Awards
- Ph.D., Biological Sciences, 1988, Stanford University
- Postdoctoral, Microbiology/Biochemistry, 1988-1991, University of Oxford
- Fulford Junior Research Fellow, 1988-1990, Somerville College, Oxford
- Jane Coffin Childs Fund for Medical Research Fellow, 1988-1991
- Marc Dresden Excellence in Graduate Education Award, 1995, Baylor College of Medicine
- The Barbara and Corbin J. Robertson Jr. Presidential Award for Excellence in Education, 2009
Mitosis to Interphase Transition
Our investigations into the mitosis to interphase transition, including chromosome conformation, spindle formation and morphological changes in the nuclear envelope, are based on our characterization of a temperature sensitive mutant, pim1-d1ts, which is defective in all of these processes. pim1 encodes a guanine nucleotide exchange factor for the small evolutionarily conserved GTPase spi1/Ran.We are identifying and characterizing the regulators and effectors of this GTPase in order to understand how it influences cell cycle progression. Because Ran influences nucleoytoplasmic transport and other cellular processes by changing the stability of import carrier/cargo complexes we are also using a variety of approaches to identify these cargo proteins.
Fission yeast undergo a closed mitosis in which the mitotic spindle forms and elongates within the nucleus, which remains intact during the entire cell cycle. During mitosis the nucleus undergoes a precise sequence of shape changes from round to oblong to peanut to dumbbell before resolving into two daughter nuclei. When the Ran GTPase system is mis-regulated the nuclear envelope breaks as cells enter mitosis. In order to better understand the physical properties of the nucleus in this abnormal situation and during normal division, we are collaborating with a group of physicists to develop a computational model to describe nuclear division and generate testable hypotheses about this process.
The Spindle Checkpoint
The spindle checkpoint is a regulatory network that monitors spindle integrity and the attachment of chromosomes to the spindle. In the presence of defects, the checkpoint system arrests cells at the metaphase to anaphase transition. We have identified two evolutionarily conserved components of this system in fission yeast, Mad2p and Mph1p. We are currently focusing on the identification of novel components of this pathway and the characterization of cells in which the checkpoint system is defective.currently characterizing 60 mutants that have the hallmark characteristics of new spindle checkpoint components.