VIRUS STRUCTURE AND ASSEMBLY

PhD student project 5
(Early Stage Researcher 5, ESR5)

VIRUS STRUCTURE AND ASSEMBLY

Supervision: Albert Heck

Early Stage Researcher: Yang Yang

  

Aim:
Understanding the biophysical processes underlying assembly of macromolecular protein complexes

Methodology:
ESR5 will take virus and virus-like assemblies as model systems. ESR5 will develop and use innovative methods, primarily based on mass spectrometry. ESR5 will measure such data for a variety of model systems (representing important pathogens or employed in gene-delivery) of increasing size and complexity and bring it together with results from complementary disciplines (X-Ray, AFM, EM, H/D MS and computational modelling) to gain in-depth new understanding of macromolecular protein assembly (collaboration Gros). For HBV we like to study the association of the virus with different antibodies and probe their binding and stoichiometry, for the triatoma virus ESR5 will use native IMMS and AFM to study the biophysical properties and (dis)assembly behaviour, comparing TrV virions and empty capsids to find out how genome packaging influences assembly and stability. For the adeno-associated virus ESR5 will investigate the stoichiometry of this heterogeneous virus that may contain different Vp1;Vp2:Vp3 ratios.

Collaborators:
Gros, Braakman; Thomas (McGill); MSVision

Key publications:

  1. C. Uetrecht, R.J. Rose, E. van Duijn, K. Lorenzen and A.J.R. Heck (2010) ‘Ion mobility mass spectrometry of proteins and protein assemblies.’ Chem Soc Rev 39, 1633-55.
  2. G.K. Shoemaker, E. van Duijn, S.E. Crawford, C. Uetrecht, M. Baclayon, W.H. Roos, G.J. Wuite, M.K. Estes, B.V. Prasad and A.J.R. Heck (2010) ‘Norwalk virus assembly and stability monitored by mass spectrometry.’ Mol Cell Proteomics 9, 1742-51.
  3. C. Uetrecht, C. Versluis, N.R. Watts, P.T. Wingfield, A.C. Steven and A.J.R. Heck (2008) ‘Stability and shape of hepatitis B virus capsids in vacuo.’ Angew Chem Int Ed Engl 47, 6247-51.