Amy S. Gladfelter | |
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Children | 2 [1] |
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Fields | Cell biology, Biophysics, Molecular Biology |
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Website | mgm |
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.
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.
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.
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. 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]
The cell nucleus is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoclasts have many. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm; and the nuclear matrix, a network within the nucleus that adds mechanical support.
Retromer is a complex of proteins that has been shown to be important in recycling transmembrane receptors from endosomes to the trans-Golgi network (TGN) and directly back to the plasma membrane. Mutations in retromer and its associated proteins have been linked to Alzheimer's and Parkinson's diseases.
Shigella flexneri is a species of Gram-negative bacteria in the genus Shigella that can cause diarrhea in humans. Several different serogroups of Shigella are described; S. flexneri belongs to group B. S. flexneri infections can usually be treated with antibiotics, although some strains have become resistant. Less severe cases are not usually treated because they become more resistant in the future. Shigella are closely related to Escherichia coli, but can be differentiated from E.coli based on pathogenicity, physiology and serology.
In cellular biology, P-bodies, or processing bodies, are distinct foci formed by phase separation within the cytoplasm of a eukaryotic cell consisting of many enzymes involved in mRNA turnover. P-bodies are highly conserved structures and have been observed in somatic cells originating from vertebrates and invertebrates, plants and yeast. To date, P-bodies have been demonstrated to play fundamental roles in general mRNA decay, nonsense-mediated mRNA decay, adenylate-uridylate-rich element mediated mRNA decay, and microRNA (miRNA) induced mRNA silencing. Not all mRNAs which enter P-bodies are degraded, as it has been demonstrated that some mRNAs can exit P-bodies and re-initiate translation. Purification and sequencing of the mRNA from purified processing bodies showed that these mRNAs are largely translationally repressed upstream of translation initiation and are protected from 5' mRNA decay.
Gideon Dreyfuss is an American biochemist, the Isaac Norris Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine, and an investigator of the Howard Hughes Medical Institute. He was elected to the National Academy of Sciences in 2012.
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.
Mitochondrial membrane transport proteins, also known as mitochondrial carrier proteins, are proteins which exist in the membranes of mitochondria. They serve to transport molecules and other factors, such as ions, into or out of the organelles. Mitochondria contain both an inner and outer membrane, separated by the inter-membrane space, or inner boundary membrane. The outer membrane is porous, whereas the inner membrane restricts the movement of all molecules. The two membranes also vary in membrane potential and pH. These factors play a role in the function of mitochondrial membrane transport proteins. There are 53 discovered human mitochondrial membrane transporters, with many others that are known to still need discovered.
The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material.
Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), is a eukaryotic protein that mediates the nuclear export of various proteins and RNAs.
Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1).
Probable ATP-dependent RNA helicase DDX20, also known as DEAD-box helicase 20 and gem-associated protein 3 (GEMIN3), is an enzyme that in humans is encoded by the DDX20 gene.
Golgi reassembly-stacking protein 1 (GORASP1) also known as Golgi reassembly-stacking protein of 65 kDa (GRASP65) is a protein that in humans is encoded by the GORASP1 gene.
Syntaxin-5 is a protein that in humans is encoded by the STX5 gene.
Citron Rho-interacting kinase is an enzyme that in humans is encoded by the CIT gene.
Anillin is a conserved protein implicated in cytoskeletal dynamics during cellularization and cytokinesis. The ANLN gene in humans and the scraps gene in Drosophila encode Anillin. In 1989, anillin was first isolated in embryos of Drosophila melanogaster. It was identified as an F-actin binding protein. Six years later, the anillin gene was cloned from cDNA originating from a Drosophila ovary. Staining with anti-anillin antibody showed the anillin localizes to the nucleus during interphase and to the contractile ring during cytokinesis. These observations agree with further research that found anillin in high concentrations near the cleavage furrow coinciding with RhoA, a key regulator of contractile ring formation.
Septin-7 is a protein that in humans is encoded by the SEPT7 gene.
The vault or vault cytoplasmic ribonucleoprotein is a eukaryotic organelle whose function is not yet fully understood. Discovered and isolated by Nancy Kedersha and Leonard Rome in 1986, vaults are cytoplasmic structures which, when negative-stained and viewed under an electron microscope, resemble the arches of a cathedral's vaulted ceiling, with 39-fold symmetry. They are present in many types of eukaryotic cells and appear to be highly conserved among eukaryotes.
Annexin A13 is a protein that in humans is encoded by the ANXA13 gene.
Gillian Margaret Griffiths is a British cell biologist and immunologist. Griffiths was one of the first to show that immune cells have specialised mechanisms of secretion, and identified proteins and mechanisms that control cytotoxic T lymphocyte secretion.
Nancy Kedersha is an American cell biologist and micrographer. She got her Ph.D. from Rutgers University where she worked in Richard Berg's lab studying the characteristics and assembly of prolyl hydroxylases. Afterwards she joined Leonard Rome's lab at UCLA as a post-doctoral fellow where she co-discovered the vault (organelle). Subsequently, she worked at ImmunoGen Inc. where she worked on staining and photographing different cancer cells. She then worked as an instructor of medicine at Brigham and Women's Hospital in Paul Anderson's lab, where her work focused on studying stress granule formation. In late-2020, she retired. In addition to her contributions as a scientist, Kedersha has been quite successful in different microscopy competitions. She is a four-time Nikon Small World finalist and in 2011 she won the Lennart Nilsson Award.
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