Scripps Research Joint Appointments

Faculty, Kellogg School of Science and Technology

Research Focus

My research involves the systematic study of the types of antibodies that are generated against the HIV envelope glycoproteins, particularly gp41, and evaluating their relative efficacy in neutralizing the virus on a case-by-case basis. In this way, we can identify weaknesses in HIV in a very specific and rational way. We can then design specific vaccine candidates that target these weaknesses and hence may elicit superior immune (antibody) responses to HIV. We develop recombinant antibody selection strategies, and, with the combination of virus neutralization assays, envelope glycoprotein mutagenesis, and other biochemical approaches, we use the new antibodies to elucidate envelope protein structure-function and uncover the molecular requirements of HIV neutralization. We have identified and characterized a number of recombinant Fabs and single-chain Fvs against the HIV-1 envelope proteins, gp120 and gp41. Significantly, we have identified novel neutralizing epitopes on the ectodomain of gp41 that are proximal to the membrane-spanning domain or that become transiently exposed during fusion. We also immunize animals with engineered immunogens in an effort to elicit HIV neutralizing antibodies.

Education

B.S., Molecular Biology, University of British Columbia, 1992
Ph.D., Molecular Biology, Simon Fraser University, 1999

Awards & Professional Activities

01/02 to 12/03 - Elizabeth Glaser Pediatric AIDS Foundation Scholarship Award;
07/01 - IAS Young Investigator Award (Travel Scholarship);
01/00 to 12/01 - Natural Sciences and Engineering Research Council of Canada Post-doctoral Fellowship (NSERC PDF);
09/98 - 12/98 Graduate Fellowship (SFU)
05/96 - 05/98 NSERC Post Graduate Scholarship (PGS B)
05/94 - 05/96 NSERC PGS A
05/92 - 08/92 Faculty of Medicine Summer Student Research Scholarship (UBC)

Selected References

Nelson JD, FM Brunel, R Jensen, ET Crooks, RMF Cardoso, M Wang, A Hessell, IA Wilson, JM Binley, PE Dawson, DR Burton, MB Zwick (2007) An affinity-enhanced neutralizing antibody against the membrane-proximal external region of human immunodeficiency virus type 1 (HIV-1) gp41 recognizes an epitope between those of 2F5 and 4E10. (In press.)

Brunel, FM, MB Zwick, RMF Cardoso, JD Nelson, IA Wilson, DR Burton, PE Dawson. (2006) Structure-function analysis of the epitope for 4E10, a broadly neutralizing human immunodeficiency virus type 1 antibody. J Virol. 80:1680-7.

Zwick MB. (2005) The membrane-proximal external region of HIV-1 gp41: a vaccine target worth exploring. AIDS. 19:1725-37.

Cardoso RM, MB Zwick, RL Stanfield, R Kunert, JM Binley, H Katinger, DR Burton, IA Wilson. (2005) Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41. Immunity. 22:163-73.