We apply a broad range of molecular biology, structural biology, and bio-imaging methods in our research. Cryogenic transmission electron microscopy (cryo-EM) is a versatile method for structural studies of small proteins, large complexes, viruses, and even organelles or sections of cells. Determining the detailed structures of different cellular components contributes to understanding of their basic functions and how these functions are impaired in disease.

How do viruses infect their host cells? In a project funded by the European Reseach Council ERC (BIZEB), we ask this question with focus on emerging viruses causing serious human illness. Despite the medical relevance of these viruses, very little is known about their detailed three-dimensional structure and infection mechanism. We use cryo-EM and X-ray crystallography to study how the viral envelope proteins bind to cell surface receptors, how their conformations change during endocytosis, how they catalyse the fusion of the viral and host-cell membranes, and how progeny viral particles bud from the infected cell to spread to new cells. Understanding of the viral infection mechanisms provides a rationale for developing antiviral strategies and understanding how viruses are neutralized by antibodies.

We coordinate a consortium funded by the Academy of Finland aiming at developing novel sample capture strategies for cryo-EM (SEMMA). These new methods are required for cellular assemblies that are too complex, rare or fragile to produce and purify by conventional heterologous expression and protein purification methods. 

Computational cryo-EM methods are best suited for solving  structures of macromolecular complexes that have high-symmetry and regular structures. We develop new tools to address structures with inherent flexibility and mismatches in symmetry. Such structures include many key cellular components as well as viruses and virus–receptor and virus–antibody complexes.