MOLECULAR ARCHITECTURE OF VIRUSES
Research Interests
Research in the Ke Lab aims to understand viral structure and function by dissecting key macromolecular complexes upon host-pathogen interactions. We will take advantage of the state-of-the-art technique of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), which allows high-resolution structure determination of macromolecules in their native environment. We are also interested in developing and applying machine learning to process low signal-to-noise ratio micrographs. Ultimately, the Ke Lab aims to uncover molecular insights into cancer-causing viral diseases, providing a basis for antiviral therapy and vaccine development.
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Below are examples of cryo-ET applications in investigating viruses and their interactions with host cells.
Journey to find a SARS-CoV-2 virion: cryo-ET
Zoom-in view from a TEM grid (3 mm in diameter) into a square (~100 µm), then into a hole (2 µm in diameter), then into a single SARS-CoV-2 virus (~100 nm in diameter).
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Images were taken from a Titan Krios transmission electron microscope operating at cryogenic temperature (around -190 ºC).
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A series of images at different tilt angles are presented, followed by a 3D tomographic reconstruction of the virion. Spike trimers protruding away from the viral membrane are visible.
SARS-CoV-2 spike protein dynamics
Spike trimer reconstruction indicates different tilt angles relative to the viral membrane. This morph animation of spike proteins indicates protein dynamics on the viral membrane, calculated based on different tilt angles derived from subtomogram averaging results.
SARS-CoV-2 variants
A comparison morph animation between the Alpha variant (B.1.1.7) and its ancestor (B.1) indicates a mutation at residue 570 induces structural changes. This was achieved by single-particle cryo-EM imaging of native virions.
HIV-1 maturation
HIV-1 Matrix protein undergoes substantial structural maturation to form very different lattices in immature and mature HIV-1. This is achieved by investigating mature and immature HIV-1 virions, followed by subtomogram averaging to high-resolution (sub-nanometer) to resolve the structural differences in these two different lattices.
Measles Virus Structural Organization
Measles virus ribonucleoprotein complex (RNP) averages and its spatial organization with Matrix lattice within a measles virus particle released from infected cells. The two colors depict the two classes of RNP with different helical pitches.
Respiratory Syncytial Virus Assembly
Respiratory syncytial virus assembly stages are captured by cryo-electron tomography from virus-infected cells. Here, initiation, elongation, assembly, and scission events are captured in one single micrograph. Green is the membrane, red is the fusion glycoprotein, and magenta is the viral ribonucleoprotein complex (RNP).