To combat viruses, host cells have developed weapons to sabotage the delivery of viral genetic code into their nuclei. There are specialised proteins that either prematurely crack open the protective viral capsid encasing the virus—exposing its genetic material to degradation—or lock the DNA in so it cannot enter the nucleus.

Till Böcking wants to understand how these and other molecular machines work.

By reconstituting these protein interactions—and watching them work using single molecule imaging—Till can see just what is required for the machines to run. He also hopes his findings will help in drug design to improve these machines and fight disease.

We develop fluorescence imaging approaches to visualise the dynamics of self-assembly processes at the single molecule level. The advantage of single molecule measurements is that they can resolve the kinetics of processes without the need for synchronisation and permit the detection of short-lived intermediates in the reaction pathways that are otherwise averaged out in traditional ensemble measurements.

Our work draws on approaches from the physical sciences with development of microfluidic imaging devices, surface chemistry approaches and development of automated image analysis software.

Current projects

  • Interactions between viral capsids and host cell machinery 
  • Pore-forming proteins in infection and immunity

Highlighted publications

  1. Dickson CF; Hertel S; Tuckwell AJ; Li N; Ruan J; Al-Izzi SC; Ariotti N; Sierecki E; Gambin Y; Morris RG; Towers GJ; Böcking T; Jacques DA, 2024, 'The HIV capsid mimics karyopherin engagement of FG-nucleoporins', Nature, 626, pp. 836 - 842, http://dx.doi.org/10.1038/s41586-023-06969-7
  2. Faysal KMR; Walsh JC; Renner N; Márquez CL; Shah VB; Tuckwell AJ; Christie MP; Parker MW; Turville SG; Towers GJ; James LC; Jacques DA; Böcking T, 2024, 'Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure', eLife, 13, http://dx.doi.org/10.7554/eLife.83605
  3. Renner N; Kleinpeter A; Mallery DL; Albecka A; Rifat Faysal KM; Böcking T; Saiardi A; Freed EO; James LC, 2023, 'HIV-1 is dependent on its immature lattice to recruit IP6 for mature capsid assembly', Nature Structural and Molecular Biology, 30, pp. 370 - 382, http://dx.doi.org/10.1038/s41594-022-00887-4
  4. Brown JWP; Alford RG; Walsh JC; Spinney RE; Xu SY; Hertel S; Berengut JF; Spenkelink LM; Van Oijen AM; Böcking T; Morris RG; Lee LK, 2022, 'Rapid Exchange of Stably Bound Protein and DNA Cargo on a DNA Origami Receptor', ACS Nano, 16, pp. 6455 - 6467, http://dx.doi.org/10.1021/acsnano.2c00699
  5. Guinness CM; Walsh JC; Bayly-Jones C; Dunstone MA; Christie MP; Morton CJ; Parker MW; Bocking T, 2022, 'Single-molecule analysis of the entire perfringolysin O pore formation pathway', eLife, 11, http://dx.doi.org/10.7554/eLife.74901

Our experts

Team members

Students

  • Martin Do (PhD Candidate)
  • Upasana Gupta (PhD Candidate)
Research Theme

Biophysics | Microbiome, Infection, Immunity and Inflammation |