The electron microscopy core (EM Core) houses and maintains all the instrumentation, in particular an FEI Tecnai F30 electron microscope with a field emission gun operating at 300 kV, needed for the recording of high-resolution images of complexes between influenza virus hemagglutin (HA) and the Fabs of neutralizing antibodies. These complexes will be analyzed either as symmetrical displays on an icosahedral scaffold or as HA rosettes.. It also contains another high-resolution instrument (an FEI Tecnai F20 that will be installed at Brandeis during the next 12 months) and two smaller instruments for sample screening. The electron microscopes will be maintained by Dr. Chen Xu (Brandeis). Furthermore, the EM Core provides computing facilities to process the image data and produce high-quality 3D reconstructions. An image processing pipeline for medium throughput processing of these structures will be set up by Dr. James Chen (Brandeis).

Public Health Relevance

Detailed 3D images of complexes between viral proteins and Fabs of neutralizing anfibodies will be privide clues about the strength of immune response to different viral anfigens. Using the 3D images, specific structural features determining the immunodominance of different epitopes will be identified. This information will be used to design new and more efficient vaccines, in particular vaccines against influenza.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01AI089618-04
Application #
8720677
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02453
Jackson, Katherine J L; Liu, Yi; Roskin, Krishna M et al. (2014) Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements. Cell Host Microbe 16:105-14
Schmidt, Aaron G; Xu, Huafeng; Khan, Amir R et al. (2013) Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody. Proc Natl Acad Sci U S A 110:264-9