We study the trafficking and interaction of molecules and structures inside cells. Extracellular signals need to be processed in a correct manner for a cell to function properly. In many cases the signals are internalised via endocytosis and then processed in a specific manner, e.g. by sorting it to a specific destination. My lab not only tries to understand these basic sorting mechanisms but also tries to exploit our understanding of these routes to deliver cargo to specific destinations in the cell. This cargo can be endogenous receptors with ligand but more recently also of viruses (Hodgson et al., 2018) and synthetic carriers (Beesley et al., 2018). 

Our research thus focuses on the visualisation and perturbation of intracellular events both at the light and electron microscopical level and as such the lab makes extensive use and develops technology in the area of live cell imaging, Correlative Light Electron Microscopy (CLEM) and 3-dimensional electron tomography (e.g. Olmos et al., 2015). One of the exciting areas is the emergence of “Structural Cell Biology” the use of Cryo Electron Microscopy to place molecular structures in its cellular context (Paul et al., 2020)

In order to be able to perform such experiments we have to develop software and hardware tools suited for the job. As such, our research is of an interdisciplinary nature and we collaborate a lot with chemists and engineers to develop such tools.

Below are some of the topics that we are currently working on:

1. To study the very early steps of endocytosis we are using Total Internal Reflection Fluorescence (TIRF) and aim to combine those with our CLEM approach.
2. The formation of tubular extensions from endosomes and lysosomes (Brown et al., 2012).
3. Development of CLEM probes that are both fluorescent and electron dense for use in intracellular transport studies (Miles et al., 2017). In collaboration with Prof. Dek Woolfson, Chemistry, UoB.
4. Targeting and delivery of molecules to specific destinations in cells, either through tagging molecules or encapsulating them (Beesley et al., 2018). This work is done in collaboration with Carmen Galan and Dek Woolfson in Chemistry.
5. Building and visualisation of new structures inside cells (Synthetic Biology, Lee et al., 2018) in collaboration with Dek Woolfson and Martin Warren (Norwich). 
6. Correct analysis and annotation is one of the keys to success in Bioimaging. We work with Alin Achim in Engineering for instance on retracing and overlay in light and electron microscopy images. (Nam et al., 2014). 

References:

- Paul, DM., Mantell, J., Borucu U., Coombs, J., Surridge, KJ., Squire, J., Verkade, P.* and Dodding MP* (2020) In situ cryo-electron tomography reveals filamentous actin within the microtubule lumen. Journal of Cell Biology, 219(9):e201911154. doi: 10.1083/jcb.201911154.   

 - 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. 

 - 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. 

 - Lee M.J., J. Mantell, L. Hodgson, D. Alibhai, J.M. Fletcher, I.R. Brown, S. Frank, W.F. Xue, P. Verkade, D.N. Woolfson, M.J. Warren (2018). Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm. Nat. Chem. Biol. doi: 10.1038/nchembio.2535. 

 - Miles, B.T., A.B. Greenwood, D. Benito, H. Tanner, M.C. Galan, P. Verkade, and H. Gersen (2017). Direct evidence of lack of colocalisation of fluorescently labelled gold labels used in Correlative Light Electron Microscopy. Scientific Reports, 7:44666, doi: 10.1038/srep44666. 

 - Olmos, Y. L. Hodgson, J. Mantell, P. Verkade, and J.G. Carlton (2015). ESCRT-III controls nuclear envelope reformation. Nature, 522: 236–239. 

 - D. Nam, J. Mantell, D. Bull, P. Verkade^*, and A. Achim^*. (2014). A Novel Framework for Segmentation of Secretory Granules in Electron Micrographs. Med Image Anal. 18:411-424.