Elizabeth R. Gavis
Director of Undergraduate Studies
Faculty AssistantMatt Montondo
- M.D., Stanford University Medical School
- Ph.D., Biochemistry, Stanford University Medical Center
- B.S., Biology, Yale University
Research AreaCell Biology, Development & Cancer
Research FocusRNA localization and translational regulation during development in Drosophila
Localization of proteins to particular subcellular domains is fundamental to the generation of asymmetry during development and to the polarization of differentiated cells. Many cell types employ localized translation of mRNAs to ensure restricted accumulation of proteins. As a model system, my laboratory studies the Drosophila nanos mRNA, whose localized translation is essential for patterning of the anterior-posterior body axis during embryonic development.
Two post-transcriptional mechanisms, intracellular mRNA localization and translational control, are coupled to produce Nanos protein solely in the posterior of the embryo. Localization of nanos RNA to the posterior pole of the oocyte/embryo is required to activate nanos translation, producing a gradient of Nanos protein that directs abdominal development. However, since only a subset of nanos mRNA is localized, translational repression of unlocalized nanos mRNA is essential to restrict synthesis of Nanos protein to the posterior and prevent deleterious effects of Nanos on head and thorax development.
Our goal is to understand the mechanisms of nanos mRNA localization and translational regulation, and how the two are linked. We have identified both a complex cis-acting mRNA localization signal and a translational control element (TCE) within the nanos 3' untranslated region (3'UTR). The TCE consists of two stem-loops: one stem-loop mediates repression during oogenesis while the other mediates repression during embryogenesis. Through both genetic screens and biochemical assays, we are now beginning to identify cellular factors that recognize these cis-acting sequences. Characterization of these factors will enable us to determine how mRNAs are targeted and transported to their destinations, how they are stabley anchored, and how their translation is regulated during this process. We have found that the TCE and associated factors interfere with a late step in the translation cycle. A similar mechanism may be used by microRNAs to repress translation of their targets. Detailed investigation of this mechanism is currently underway.
To investigate nanos localization at the cell biological level, we have applied a method for in vivo labeling of mRNAs with GFP. The ability to visualize GFP-labeled nanos mRNA in living oocytes has permitted dynamic analysis of RNA localization in real time and determination of the cytoskeletal requirements for localization and anchoring. We have recently extended these studies to bicoid mRNA, whose localization to the anterior of the oocyte appears to occur by a distinct mechanism.
Recent work has shown that nanos is required in a set of peripheral neurons for dendritic morphogenesis and that the TCE can mediate repression of nanos in these neurons. We are investigating whether nanos mRNA and protein are localized within the dendrites and how the TCE functions in this tissue. Based on ectopic expression studies showing that the TCE can function in several other tissues as well, we are attempting to identify additional mRNAs that are subject to TCE-mediated regulation.
Distinct -acting elements mediate targeting and clustering of polar granule mRNAs. Development. 2018 ;. .
Stochastic Seeding Coupled with mRNA Self-Recruitment Generates Heterogeneous Drosophila Germ Granules. Curr Biol. 2018 ;28(12):1872-1881.e3. .
Enclosure of Dendrites by Epidermal Cells Restricts Branching and Permits Coordinated Development of Spatially Overlapping Sensory Neurons. Cell Rep. 2017 ;20(13):3043-3056. .
Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation. Cell Rep. 2017 ;20(4):935-948. .
Germ Cell-less Promotes Centrosome Segregation to Induce Germ Cell Formation. Cell Rep. 2017 ;18(4):831-839. .
The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition. Cell Rep. 2017 ;19(1):150-161. .
A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis. G3 (Bethesda). 2016 ;6(8):2397-405. .
Fixed and live visualization of RNAs in Drosophila oocytes and embryos. Methods. 2016 ;98:34-41. .
Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals. Development. 2016 ;143(12):2147-59. .
Independent and coordinate trafficking of single Drosophila germ plasm mRNAs. Nat Cell Biol. 2015 ;17(5):558-68. .
Extensive use of RNA-binding proteins in Drosophila sensory neuron dendrite morphogenesis. G3 (Bethesda). 2014 ;4(2):297-306. .
Germ plasm anchoring is a dynamic state that requires persistent trafficking. Cell Rep. 2013 ;5(5):1169-77. .
Elizabeth Gavis (Liz) is a Professor in the Department of Molecular Biology and an Associated Faculty of the Princeton Neuroscience Institute at Princeton University. Liz became hooked on research during a summer internship at the Carnegie Institute for Embryology, just after graduating from high school. She majored in Biology at Yale University, continuing her work at the Carnegie Institute and then at Johns Hopkins University Medical School during the summer. These experiences led her to enter the MSTP and the Biochemistry Department at Stanford University Medical School, where she earned MD and PhD degrees. After a postdoctoral fellowship at the Whitehead Institute at MIT, Liz joined the Princeton faculty in 1994.
Liz's research focuses on understanding genetic regulatory mechanisms that underlie the development of a properly formed animal from a fertilized egg, with a focus on post-transcriptional control of gene expression. In addition to mentoring students and postdocs in the lab, she teaches one of the largest courses at Princeton – "Introduction to Molecular and Cellular Biology" – as well as a popular graduate level genetics course that she developed with her colleague Eric Wieschaus. Liz helped found the joint Princeton/Rutgers University MD/PhD program and served as its Princeton director. She served as President of the Drosophila Board of Directors, on which she remains active, and is a member of the Board of Directors of the Society of Developmental Biology. Liz also serves on several editorial boards and participates in mentorship programs for women in science at Princeton, Hunter College, and The College of New Jersey.
- Innovation Award, Department of Molecular Biology, Princeton University
- President, The North American Drosophila Board of Directors