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Organelle sorting and interconnectivity

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

About This PhD Project

Project Description

Following internalisation of receptor-bound ligands into early endosomes Epidermal Growth Factor (EGF) is internalised into multi-vesicular bodies and degraded. Transferrin (Tf) however is sorted away from the endosome and recycled back to the plasma membrane. Using a Correlative Light Electron Microscopy approach (CLEM, Verkade, 2008) we found that there may be a direct connection between recycling endosomes and the plasma membrane (see Figure and Brown et al., 2012). This had not been observed before and we want to study whether this is a common mechanism and how such recycling would be regulated. The underlying sorting machinery is key in this sorting and we have created a new labelling technique that should allow visualisation of this machinery in the light and electron microscope.

SAGEs are peptide vesicles that may be used for drug delivery (Beesley et al., 2017), however strategies to let cargo escape from the endosome into the cytosol have so far been unsuccessful. The cell’s defence mechanisms (membrane repair, e.g. Galectins) appear to be stronger than the escape. We would like to understand this mechanism better so we can use that to our advantage in the design of drug delivery carriers.

My lab specialises in CLEM technology and we apply this to a wide variety of biological questions. We do this in collaboration with a number of collaborators within the faculty and beyond (e.g. Yamauchi (Hodgson et al., 2018), Dodding, Wuelfing, Hanley, Hanley, Cullen in the faculty of Life Sciences). All of these projects look at the interaction of organelles and the molecules inside them and are critically dependent on high-end imaging technology.

References

P. Verkade. (2008). Moving EM: The Rapid Transfer System as a New Tool for Correlative Light and Electron Microscopy and High Throughput for High-Pressure Freezing. Journal of Microscopy. 230: 317-328.

Brown, E., J., Van Weering, T. Sharp, J. Mantell, and P. Verkade (2012). Capturing endocytic segregation events with HPF-CLEM. Methods in Cell Biology, Volume 111: Correlative Light and Electron Microscopy, 175-201.

Beesley JL, Baum HE, Hodgson LR, Verkade P, Banting GS, Woolfson DN (2018). Modifying Self-Assembled Peptide Cages To Control Internalization into Mammalian Cells. Nano letters. doi: 10.1021/acs.nanolett.8b02633.

Hodgson L., P. Verkade, Y. Yamauchi (2018) Correlative light and electron microscopy of influenza viris entry and budding. Methods in Molecular Biology, Volume 1836: Influenza virus, 237-260.

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