Browsing by Author "Kunze, Anja"

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Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection
(Springer Science and Business Media LLC, 2023-10) Hashimi, Marziah; Sebrell, T. Andrew; Hedges, Jodi F.; Snyder, Deann; Lyon, Katrina N.; Byrum, Stephanie D.; Mackintosh, Samuel G.; Crowley, Dan; Cherne, Michelle D.; Skwarchuk, David; Robison, Amanda; Sidar, Barkan; Kunze, Anja; Loveday, Emma K.; Taylor, Matthew P.; Chang, Connie B.; Wilking, James N.; Walk, Seth T.; Schountz, Tony; Jutila, Mark A.; Bimczok, Diane
Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat (JFB, Artibeus jamaicensis) intestinal organoid model of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Upon infection with SARS-CoV-2, increased viral RNA and subgenomic RNA was detected, but no infectious virus was released, indicating that JFB organoids support only limited viral replication but not viral reproduction. SARS-CoV-2 replication was associated with significantly increased gene expression of type I interferons and inflammatory cytokines. Interestingly, SARS-CoV-2 also caused enhanced formation and growth of JFB organoids. Proteomics revealed an increase in inflammatory signaling, cell turnover, cell repair, and SARS-CoV-2 infection pathways. Collectively, our findings suggest that primary JFB intestinal epithelial cells mount successful antiviral interferon responses and that SARS-CoV-2 infection in JFB cells induces protective regenerative pathways.
Force-Mediating Magnetic Nanoparticles to Engineer Neuronal Cell Function
(2018-05) Gahl, Trevor J.; Kunze, Anja
Cellular processes like membrane deformation, cell migration, and transport of organelles are sensitive to mechanical forces. Technically, these cellular processes can be manipulated through operating forces at a spatial precision in the range of nanometers up to a few micrometers through chaperoning force-mediating nanoparticles in electrical, magnetic, or optical field gradients. But which force-mediating tool is more suitable to manipulate cell migration, and which, to manipulate cell signaling? We review here the differences in forces sensation to control and engineer cellular processes inside and outside the cell, with a special focus on neuronal cells. In addition, we discuss technical details and limitations of different force-mediating approaches and highlight recent advancements of nanomagnetics in cell organization, communication, signaling, and intracellular trafficking. Finally, we give suggestions about how force-mediating nanoparticles can be used to our advantage in next-generation neurotherapeutic devices.
Modulating motility of intracellular vesicles in cortical neurons with nanomagnetic forces on-chip
(2017-02) Kunze, Anja; Murray, Coleman Tylor; Godzich, Chanya; Lin, Jonathan; Owsley, Keegan; Tay, Andy; Di Carlo, Dino
Vesicle transport is a major underlying mechanism of cell communication. Inhibiting vesicle transport in brain cells results in blockage of neuronal signals, even in intact neuronal networks. Modulating intracellular vesicle transport can have a huge impact on the development of new neurotherapeutic concepts, but only if we can specifically interfere with intracellular transport patterns. Here, we propose to modulate motion of intracellular lipid vesicles in rat cortical neurons based on exogenously bioconjugated and cell internalized superparamagnetic iron oxide nanoparticles (SPIONs) within microengineered magnetic gradients on-chip. Upon application of 6-126 pN on intracellular vesicles in neuronal cells, we explored how the magnetic force stimulus impacts the motion pattern of vesicles at various intracellular locations without modulating the entire cell morphology. Altering vesicle dynamics was quantified using, mean square displacement, a caging diameter and the total traveled distance. We observed a de-acceleration of intercellular vesicle motility, while applying nanomagnetic forces to cultured neurons with SPIONs, which can be explained by a decrease in motility due to opposing magnetic force direction. Ultimately, using nanomagnetic forces inside neurons may permit us to stop the mis-sorting of intracellular organelles, proteins and cell signals, which have been associated with cellular dysfunction. Furthermore, nanomagnetic force applications will allow us to wirelessly guide axons and dendrites by exogenously using permanent magnetic field gradients.
Multi-curvature micropatterns unveil distinct calcium and mitochondrial dynamics in neuronal networks
(Royal Society of Chemistry, 2021-01) Khan, Hammad; Beck, Connor; Kunze, Anja
Soft-embossed highly-parallelized multi-curvature micropatterns model the impact of different curvatures (k = 0.003–0.2 μm−1) inspired by the human cerebral tissue folds on changes in spontaneous neuronal calcium signals and mitochondrial transport.