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 fungusAshbya 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. They predicted that virus ability to store information came from the use of nucleic acid sequences and RNA structure to encode different condensate-dependent functions. Gladfelter ultimately assumed that these functions would increase biochemical complexity, and would assist in performing multiple roles within a single cell, while only utilizing a few cellular components.[19]
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.[20][21][22] Gladfelter's lab discovered that septins are able to self-organize after deliberate disruption using an HS-AFM (high-speed atomic force microscope). The septins used their remaining pieces to self-template and reorganize into their original configuration.[23]
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