Research Associate - Institute of Human Virology
Education and Training
My work has concerned the molecular mechanisms of protein toxin translocation. After completion of my Masters in Chemistry at the University of York (2005), I undertook a PhD in Biology at the University of York (in the laboratory of Prof. Colin Kleanthous, now at Oxford University) studying the translocation mechanism of the Colicin E9 protein. Specifically, I investigated how Colicin E9 parasitized the Tol-Pal system in the periplasm in order to achieve internalization.
After completion of my PhD, I joined Dr. Eric Sundberg at the Boston Biomedical Research Institute, in 2009, to examine the interaction of directly evolved T-cell receptor that binding to Toxic Shock Syndrome proteins from Streptococcus pyogenes and Staphylococcus aureus. It was here that we began research on the translocation mechanism of the oncogenic protein CagA, from Helicobacter pylori, through a Type Four Secretion System.
This research continued when the Sundberg lab moved to the University of Maryland, Baltimore in 2011. My research has focused on several other proteins of the Type Four Secretion System as well as a group of human proteins which are displayed on epithelial cell surfaces that are essential for the translocation of CagA.
My research utilizes my expertise in protein expression and purification to characterize these proteins using a suite of biophysical techniques including; Isothermal titration calorimetry; Analytical ultracentrifugation; X-ray crystallography; Small angle X-ray scattering; Cyro electron-microscopy.
CagA is injected by H. pylori through a Type Four Secretion System into host gastric epithelial cells where is perturbs several host signaling pathways including the dysregulation of kinase-dependent signal transduction cascades and the apoptotic program, causing the majority of all diagnosed gastric cancers. We have been investigating how CagA is delievered through the Type Four Secretion System, specifically the interaction with its chaperone, CagF, a protein which is essential for CagA’s successful translocation. We have also investigated the role of CagL, which decorates the pilus of the Type Four Secretion System that is also required for CagA translocation.
Our collaborators recently identified the HopQ protein from H. pylori which too is vital for CagA translocation. HopQ is unusual as it not part of the Type Four Secretion System operons in H. pylori. They identified HopQ interacts with a family of host cell surface proteins called carcinoembryonic antigen-related cell adhesion molecules (CEACAMs). We have solved crystal structures of several CEACAMs as well as complexes between HopQ and CEACAMs. CEACAMs have been identified not only as receptors for several pathogenic bacteria such as Escherichia coli, Moraxella catarrhalis, Neisseria meningitides and Neisseria gonorrhoeae, but are also deregulated in many cancers.
Helicobacter pylori, CEACAMs, X-ray crystallography
Daniel A. Bonsor, Qing Zhao, Barbara Schmidinger, Evelyn Weiss, Jingheng Wang, Daniel Deredge, Robert Beadenkopf, Blaine Dow, Wolfgang Fischer, Dorothy Beckett, Patrick L. Wintrode, Rainer Haas, Eric J. Sundberg (2018). The Helicobacter pylori adhesin protein HopQ exploits the dimer interface of human CEACAMs to facilitate translocation of the oncoprotein CagA. EMBO Journal, 37(13), e98664
Daniel A. Bonsor, Sebastian Günther, Robert Beadenkopf, Dorothy Beckett and Eric J. Sundberg (2015). Diverse oligomeric states of CEACAM IgV domains. Proceedings of the National Academy of Sciences of the United States of America, 112(44), 13561-13566
Daniel A. Bonsor, Kieu T. Pham, Robert Beadenkopf, Kay Diederichs, Rainer Haas, Dorothy Beckett, Wolfgang Fischer, and Eric J. Sundberg (2015). Integrin engagement by a helical RGD motif is regulated by a pH-induced displacement of a neighboring alpha helix. Journal of Biological Chemistry, 290(20), 12929-12940.
Daniel A. Bonsor, Evelyn Weiss, Anat Iosub-Amir, Tali H. Reingewertz, Tiffany W. Chen, Rainer Haas, Assaf Friedler, Wolfgang Fischer, Eric J. Sundberg (2013). Characterization of the translocation-competent complex between the Helicobacter pylori oncogenic protein CagA and the accessory protein CagF. Journal of Biological Chemistry, 288(46) 32897-32909.