PEOPLE
Wes Sundquist, Director
Pamela Bjorkman Debbie Eckert Nels Elde Adam Frost Chris Hill Tom Hope Janet Iwasa Grant Jensen Michael Kay Anthony Kossiakoff Neil King Walther Mothes Elisabetta Viani Puglisi Barbie Ganser-Pornillos Greg Voth Mark Yeager Scientific Advisory Board Collaborative Development Program Awardees |
Pamela Bjorkman
Our laboratory is interested in protein-protein interactions, particularly those mediating immune recognition. We use X-ray crystallography and biochemistry to study purified proteins, and electron and confocal microscopy to examine protein complexes in cells. Following upon our electron tomography (ET) studies of receptor-mediated transport of IgG across intestinal epithelial cells, we are now conducting ET imaging studies of HIV-1-infected human tissue and equivalent samples from humanized mouse models to characterize sites of infection at high resolution during a natural infection. We are focusing on gut-associated lymphoid tissue, which is an early site for HIV replication and CD4 T-cell depletion and using immuno-EM to identify HIV virions and cell subtypes of interest (e.g., the Th17 subset of CD4 T-cells) to determine which cells are infected and subsequently involved in large amounts of viral budding and dissemination). Topics that can be addressed by 3-D imaging of HIV-infected tissues include: (i) quantitative analysis of numbers and types of infected cells, including their positions with respect to each other and within the tissue as a function of the length of infection, viral load, and the presence or absence of anti-retroviral drugs; (ii) quantitative analyses of global viral location and state (i.e., intracellular versus extracellular locations, numbers of fusing versus budding virions, and immature versus mature viruses), again as a function of length of infection and the presence or absence of anti-retroviral drugs; (iii) mapping routes of virus trafficking in infected cells with respect to cell boundaries and how the ultrastructure of those cells is altered during the course of the HIV replication cycle; (iv) comparisons of budding of HIV from the plasma membrane versus into intracellular locations as a function of cell type; and (v) quantitative comparisons of virus transmission during the course of infection, which may be pertinent to understanding the propensity for viral spread via cell-to-cell transmission or infection by free virions within different tissues or organs.
Pamela Bjorkman, PhD Howard Hughes Medical Institute Division of Biology and Biological Engineering, 114-96 California Institute of Technology 1200 E. California Blvd. Pasadena, CA 91125 Phone: (626)395-8350 Fax: (626)792-3683 Email: bjorkman@caltech.edu Lab webpage: http://www.its.caltech.edu/~bjorker/  |