BioNanopatterning: My lab focusses on developing DNA nanotechnology to understand and exploit the human innate immune system. Protein nanopatterns are essential for cellular function, and recent research indicates that our immune system is activated by nanopatterned antibody platforms. We are using DNA to determine structure-function relationships between antigen nanopatterns and immune system activation, and developing methods to exploit this activation.
Visualizing complement activation in the act: Using state of the art phase-plate electron cryo-tomography We are solving various structures of IgM in the act of activating our immune system.
Super-resolution cryoCLEM: We are also working to combine the burgeoning fields of super-resolution light microscopy with cryoEM to achieve high-accuracy localization of tagged proteins within samples prepared for cryoEM. This will allow us to perform structural biology on individual proteins within cells.
Thom Sharp is an assistant professor at the LUMC and head of the BioNanoPatterning group. At the LUMC, before starting the BioNanoPatterning lab, Thom’s research focussed on the use of electron cryo-tomography, combined with subtomogram averaging, to determine the structures of different macromolecular protein complexes of the innate immune system. Before moving to the Netherlands, Thom was a postdoc at the University of Oxford, UK, where he worked in the Division of Structural Biology (STRUBI) and the Department of Physics with Andrew Turberfield. Whilst there he designed and tested DNA-templated protein arrays as a tool for high-throughput protein structure determination using cryoTEM and single-particle analysis. Thom performed his PhD jointly between the groups of Dek Woolfson (Chemistry) and Paul Verkade (Biochemistry) at the University of Bristol, UK focussing on the utilisation of cryoEM to elucidate the superstructure of self-assembled peptide fibres, and the development of new in vivo probes for Correlative Light Electron Microscopy (CLEM).
Please contact Thomas Sharp for copies of any of our publications (email@example.com)
One-Pot Synthesis of Defined-Length ssDNA for Multiscaffold DNA Origami.
W.E.M. Noteborn, L. Abendstein and T.H. Sharp*.
Bioconjugate Chem. 2021, 32, 1, 94–98
Insights into IgM-mediated complement activation based on in situ structures of IgM-C1-C4b.
T.H. Sharp*, A.L. Boyle, C.A. Diebolder, A. Kros, A.J. Koster, P. Gros.
Proceedings of the National Academy of Sciences (2019). 116 (24), pp. 11900-11905
Correlative cryo super-resolution light and electron microscopy on mammalian cells using fluorescent proteins.
M.W. Tuijtel, A.J. Koster, S. Jakobs, F.G.A. Faas and T.H. Sharp*.
Scientific reports (2019) 9 (1), pp. 1-11