Amy Gladfelter

Last updated

Amy S. Gladfelter
Amy Gladfelter headshot 2018.jpg
Born (1974-04-27) April 27, 1974 (age 50)
Alma mater
Children2 [1]
Awards
Scientific career
FieldsCell biology, Biophysics, Molecular Biology
Institutions
Website mgm.duke.edu/personnel/amy-gladfelter-phd

Amy S. Gladfelter (born April 27, 1974) is an American quantitative cell biologist who is interested in understanding fundamental mechanisms of cell organization. She was a Professor of Biology and the Associate Chair for Diversity Initiatives at the University of North Carolina at Chapel Hill, before moving to Department of Cell Biology at Duke University. [5] She investigates cell cycle control and the septin cytoskeleton. [6] She is also affiliated with the Lineberger Comprehensive Cancer Center and is a fellow of the Marine Biological Laboratory in Woods Hole, MA.

Contents

Gladfelter studies the spatial organization of multinucleate cells, also called syncytia, which are cells with many nuclei that share a common cytoplasm. Her lab at Duke University is broadly interested in understanding why syncytia have arisen in diverse contexts within the tree of life. [7] [8] [9] [10]   Syncytial cells are found throughout the human body, including in bone, blood, muscle, and placental tissue, and throughout the natural world, including in fungi, algae and in many animals during their development. Many tumors become syncytial, while certain viruses, including SARS-CoV-2, can induce cells to fuse.  Additionally, Gladfelter studies the assembly of the septin cytoskeleton and how aberrant septin structure affects its function. [11] [12] [13] [14] [15] [16] Her research program uses microscopy, biophysical and genetic approaches to study cell biology.

Education

Amy Gladfelter trained at Princeton University (AB) with Bonnie Bassler, at Duke University (Ph.D.) with Daniel Lew and at UniBasel Biozentrum (post-doc) with Peter Philippsen before starting her independent career at Dartmouth in the Biological Sciences department in 2006, where she remained until 2016.

Cell biology research

The two main research focuses of the Gladfelter lab are how the cytoplasm is spatially organized and how cells sense their own geometry. Her team uses a variety of model systems to study syncytia, including Ashbya gossypii, Neurospora crassa, myotubes and the syncytiotrophoblast of human placenta to study the architecture of the cytoplasm. Gladfelter is also seeking out new fungal systems derived from the marine environment that are extremophiles and show morphologic characteristics not found in more conventional model systems. [17]

Gladfelter made the discovery that the nuclei of the multinucleate fungus Ashbya gossypii, despite sharing the same cytoplasm, progress through the cell cycle independently. [18] This has led to further work uncovering how liquid-liquid phase separation of RNAs and proteins can permit autonomy among syncytial nuclei and help to establish cell polarity. Recently, the lab has begun examining phase separation in the context of SARS-CoV-2 infection, with a focus on understanding mechanisms of viral packaging.

Another area that Gladfelter's lab explores is how cells sense their shape. [7] Gladfelter and her lab have extensively studied the ability of a conserved family of proteins called septins, which localize to areas of the cell that change shape or are highly curved, to sense cell curvature. [19] [20] [21]

Awards and honors

Selected works

On cytoplasmic organization
On cell shape and septin assembly

Related Research Articles

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<span class="mw-page-title-main">Retromer</span>

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Septins are a group of GTP-binding proteins expressed in all eukaryotic cells except plants. Different septins form protein complexes with each other. These complexes can further assemble into filaments, rings and gauzes. Assembled as such, septins function in cells by localizing other proteins, either by providing a scaffold to which proteins can attach, or by forming a barrier preventing the diffusion of molecules from one compartment of the cell to another, or in the cell cortex as a barrier to the diffusion of membrane-bound proteins.

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References

  1. Sedwick, Caitlin (February 17, 2014). "Amy Gladfelter: Fungi with a streak of individuality". Journal of Cell Biology. 204 (4): 464–465. doi:10.1083/jcb.2044pi. PMC   3926962 . PMID   24535821.
  2. 1 2 "The 2016 Faculty Scholars". Howard Hughes Medical Institute. Retrieved November 30, 2017.
  3. 1 2 "Faculty Mentoring Award". Dartmouth. Archived from the original on December 28, 2017. Retrieved November 30, 2017.
  4. 1 2 Chapman, Keith (July 20, 2012). "Ten Professors Honored with Faculty Awards". Dartmouth. Dartmouth News. Retrieved November 30, 2017.
  5. "The Gladfelter Lab". The Gladfelter Lab. Retrieved February 15, 2024.
  6. "The Gladfelter Lab". The University of North Carolina at Chapel Hill. Retrieved November 30, 2017.
  7. 1 2 "Research Questions". The Gladfelter Lab. Retrieved October 8, 2019.
  8. Lee, Changhwan; Zhang, Huaiying; Baker, Amy E.; Occhipinti, Patricia; Borsuk, Mark E.; Gladfelter, Amy S. (June 24, 2013). "Protein aggregation behavior regulates cyclin transcript localization and cell-cycle control". Developmental Cell. 25 (6): 572–584. doi:10.1016/j.devcel.2013.05.007. ISSN   1878-1551. PMC   4113091 . PMID   23769973.
  9. Zhang, Huaiying; Elbaum-Garfinkle, Shana; Langdon, Erin M.; Taylor, Nicole; Occhipinti, Patricia; Bridges, Andrew A.; Brangwynne, Clifford P.; Gladfelter, Amy S. (October 15, 2015). "RNA Controls PolyQ Protein Phase Transitions". Molecular Cell. 60 (2): 220–230. doi:10.1016/j.molcel.2015.09.017. ISSN   1097-4164. PMC   5221516 . PMID   26474065.
  10. Langdon, Erin M.; Qiu, Yupeng; Ghanbari Niaki, Amirhossein; McLaughlin, Grace A.; Weidmann, Chase A.; Gerbich, Therese M.; Smith, Jean A.; Crutchley, John M.; Termini, Christina M.; Weeks, Kevin M.; Myong, Sua (May 25, 2018). "mRNA structure determines specificity of a polyQ-driven phase separation". Science. 360 (6391): 922–927. Bibcode:2018Sci...360..922L. doi:10.1126/science.aar7432. ISSN   1095-9203. PMC   6192030 . PMID   29650703.
  11. Gladfelter, Amy S.; Bose, Indrani; Zyla, Trevin R.; Bardes, Elaine S. G.; Lew, Daniel J. (January 21, 2002). "Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p". The Journal of Cell Biology. 156 (2): 315–326. doi:10.1083/jcb.200109062. ISSN   0021-9525. PMC   2199227 . PMID   11807094.
  12. DeMay, Bradley S.; Meseroll, Rebecca A.; Occhipinti, Patricia; Gladfelter, Amy S. (April 2009). "Regulation of distinct septin rings in a single cell by Elm1p and Gin4p kinases". Molecular Biology of the Cell. 20 (8): 2311–2326. doi:10.1091/mbc.e08-12-1169. ISSN   1939-4586. PMC   2669037 . PMID   19225152.
  13. DeMay, Bradley S.; Bai, Xiaobo; Howard, Louisa; Occhipinti, Patricia; Meseroll, Rebecca A.; Spiliotis, Elias T.; Oldenbourg, Rudolf; Gladfelter, Amy S. (June 13, 2011). "Septin filaments exhibit a dynamic, paired organization that is conserved from yeast to mammals". The Journal of Cell Biology. 193 (6): 1065–1081. doi:10.1083/jcb.201012143. ISSN   1540-8140. PMC   3115802 . PMID   21670216.
  14. Meseroll, Rebecca A.; Occhipinti, Patricia; Gladfelter, Amy S. (February 2013). "Septin phosphorylation and coiled-coil domains function in cell and septin ring morphology in the filamentous fungus Ashbya gossypii". Eukaryotic Cell. 12 (2): 182–193. doi:10.1128/EC.00251-12. ISSN   1535-9786. PMC   3571309 . PMID   23204191.
  15. Bridges, Andrew A.; Zhang, Huaiying; Mehta, Shalin B.; Occhipinti, Patricia; Tani, Tomomi; Gladfelter, Amy S. (February 11, 2014). "Septin assemblies form by diffusion-driven annealing on membranes". Proceedings of the National Academy of Sciences of the United States of America. 111 (6): 2146–2151. Bibcode:2014PNAS..111.2146B. doi: 10.1073/pnas.1314138111 . ISSN   1091-6490. PMC   3926015 . PMID   24469790.
  16. McQuilken, Molly; Jentzsch, Maximilian S.; Verma, Amitabh; Mehta, Shalin B.; Oldenbourg, Rudolf; Gladfelter, Amy S. (2017). "Analysis of Septin Reorganization at Cytokinesis Using Polarized Fluorescence Microscopy". Frontiers in Cell and Developmental Biology. 5: 42. doi: 10.3389/fcell.2017.00042 . ISSN   2296-634X. PMC   5413497 . PMID   28516085.
  17. Gladfelter, Amy S.; James, Timothy Y.; Amend, Anthony S. (March 2019). "Marine fungi". Current Biology. 29 (6): R191–R195. doi: 10.1016/j.cub.2019.02.009 . ISSN   0960-9822. PMID   30889385.
  18. Gladfelter, Amy; Hungerbuehler, Katrin; Philippsen, Peter (January 30, 2006). "Asynchronous nuclear division cycles in multinucleated cells". The Journal of Cell Biology. 172 (3): 347–362. doi:10.1083/jcb.200507003. PMC   2063645 . PMID   16449188.
  19. Ewers, Helge; Tada, Tomoko; Petersen, Jennifer D.; Racz, Bence; Sheng, Morgan; Choquet, Daniel (2014). "A Septin-Dependent Diffusion Barrier at Dendritic Spine Necks". PLOS ONE. 9 (12): e113916. Bibcode:2014PLoSO...9k3916E. doi: 10.1371/journal.pone.0113916 . ISSN   1932-6203. PMC   4262254 . PMID   25494357.
  20. Hu, Qicong; Milenkovic, Ljiljana; Jin, Hua; Scott, Matthew P.; Nachury, Maxence V.; Spiliotis, Elias T.; Nelson, W. James (July 23, 2010). "A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution". Science. 329 (5990): 436–439. Bibcode:2010Sci...329..436H. doi:10.1126/science.1191054. ISSN   1095-9203. PMC   3092790 . PMID   20558667.
  21. Takizawa, P. A.; DeRisi, J. L.; Wilhelm, J. E.; Vale, R. D. (October 13, 2000). "Plasma membrane compartmentalization in yeast by messenger RNA transport and a septin diffusion barrier". Science. 290 (5490): 341–344. Bibcode:2000Sci...290..341T. doi:10.1126/science.290.5490.341. ISSN   0036-8075. PMID   11030653.
  22. "NSF Award Search: Award#0301028 - Postdoctoral Research Fellowship in Microbial Biology for FY 2003". www.nsf.gov. Retrieved October 8, 2019.
  23. "2010 MBL Research Awards". Marine Biological Laboratory. Retrieved November 30, 2017.
  24. "2011 MBL Research Awards". Marine Biological Laboratory. Retrieved November 30, 2017.
  25. "2012 MBL Research Awards". Marine Biological Laboratory. Retrieved November 30, 2017.
  26. "Amy Gladfelter". Marine Biology Laboratory. Retrieved November 30, 2017.