Recommended Readings: Shixin Liu, Ph.D. September 29

Special Seminar
Monday, September 29, 2014
4:00 p.m., Carson Family Auditorium

Shixin Liu, Ph.D.
Postdoctoral Fellow,
California Institute for Quantitative Biosciences (QB3),
University of California, Berkeley

Visualization and Manipulation of Single Biomolecular Machines

Recommended Readings

Empirical Articles

Chistol, G., Liu, S., Hetherington, C. L., Moffitt, J. R., Grimes, S., Jardine, P. J., & Bustamante, C. (2012). High degree of coordination and division of labor among subunits in a homomeric ring ATPase. Cell, 151(5), 1017–1028. doi:10.1016/j.cell.2012.10.031

Liu, S., Abbondanzieri, E., & Rausch, J. (2008). Slide into action: dynamic shuttling of HIV reverse transcriptase on nucleic acid substrates. Science, 322(5904):1092-1097. doi: 10.1126/science.1163108.

Liu, S., Chistol, G., Hetherington, C. L., Tafoya, S., Aathavan, K., Schnitzbauer, J., … Bustamante, C. (2014). A viral packaging motor varies its DNA rotation and step size to preserve subunit coordination as the capsid fills. Cell, 157(3), 702–713. doi:10.1016/j.cell.2014.02.034

Liu, S., Harada, B. T., Miller, J. T., Le Grice, S. F. J., & Zhuang, X. (2010). Initiation complex dynamics direct the transitions between distinct phases of early HIV reverse transcription. Nature Structural & Molecular Biology, 17(12), 1453–60. doi:10.1038/nsmb.1937

Review Papers

Liu, S., Chistol, G., & Bustamante, C. (2014). Mechanical operation and intersubunit coordination of ring-shaped molecular motors: insights from single-molecule studies. Biophysical Journal, 106(9), 1844–58. doi:10.1016/j.bpj.2014.03.029

Recommended Readings: David D. Ho, M.D. April 21

Monday Lecture Series
Monday, April 21, 2014
4:00 p.m., Carson Family Auditorium

David D. Ho, M.D.
Irene Diamond Professor
Senior Physician
Scientific Director
Chief Executive Officer
Aaron Diamond AIDS Research Center
The Rockefeller University

Long-acting Antibodies and Drugs as Prophylactics in HIV Prevention

Recommended Readings:

Empirical Papers

Andrews, C. D., Spreen, W. R., Mohri, H., Moss, L., Ford, S., Gettie, A., … Ho, D. D. (2014). Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus. Science, 343(6175), 1151–1154. doi:10.1126/science.1248707

Baeten, J. M., Donnell, D., Ndase, P., Mugo, N. R., Campbell, J. D., Wangisi, J., … Celum, C. (2012). Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. The New England Journal of Medicine, 367(5), 399–410. doi:10.1056/NEJMoa1108524

Grant, R. M., Lama, J. R., Anderson, P. L., McMahan, V., Liu, A. Y., Vargas, L., … Glidden, D. V. (2010). Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. The New England Journal of Medicine, 363(27), 2587–2599. doi:10.1056/NEJMoa1011205

Song, R., Oren, D. a, Franco, D., Seaman, M. S., & Ho, D. D. (2013). Strategic addition of an N-linked glycan to a monoclonal antibody improves its HIV-1-neutralizing activity. Nature Biotechnology, 31(11), 1047–1052. doi:10.1038/nbt.2677

Review Articles

Spreen, W. R., Margolis, D. a, & Pottage, J. C. (2013). Long-acting injectable antiretrovirals for HIV treatment and prevention. Current Opinion in HIV and AIDS, 8(6), 565–571. doi:10.1097/COH.0000000000000002

Recommended Readings: Michel C. Nussenzweig, M.D., Ph.D.

Friday Lecture Series

Ph.D. Recruitment Lecture

The HIV Vaccine Problem

Michel C. Nussenzweig, M.D., Ph.D., Sherman Fairchild Professor,

senior physician, The Rockefeller University;

investigator, Howard Hughes Medical Institute

 March 8, 2012

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium


Recommended Readings

Mouquet, H., Warncke, M., Scheid, J. F., Seaman, M. S., & Nussenzweig, M. C. (2012). Enhanced HIV-1 neutralization by antibody heteroligation. Proceedings of the National Academy of Sciences of the United States of America, 109(3), 875-880

Nchinda, G., Kuroiwa, J., Oks, M., Trumpfheller, C., Chae, G. P., Huang, Y., . . . Steinman, R. M. (2008). The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells. Journal of Clinical Investigation, 118(4), 1427-1436

Scheid, J. F., Mouquet, H., Ueberheide, B., Diskin, R., Klein, F., Oliveira, T. Y. K., . . . Nussenzweig, M. C. (2011). Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science, 333(6049), 1633-1637

Trumpfheller, C., Finke, J. S., López, C. B., Moran, T. M., Moltedo, B., Soares, H., . . . Steinman, R. M. (2006). Intensified and protective CD4 + T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine. Journal of Experimental Medicine, 203(3), 607-617

Zhou, T., Georgiev, I., Wu, X., Yang, Z. -., Dai, K., Finzi, A., . . . Kwong, P. D. (2010). Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science, 329(5993), 811-817

Recommended Readings: Bruce Walker, M.D.

Friday Lecture Series

Immune Control and Immune Failure in HIV Infection

Bruce Walker, M.D., Principal Investigator,

Ragon Institute of MGH, MIT and Harvard

April 13, 2012

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium


Recommended Readings:

Huang, J., P. S. Burke, T. D. H. Cung, F. Pereyra, I. Toth, B. D. Walker, L. Borges, M. Lichterfeld, and X. G. Yu. 2010. “Leukocyte Immunoglobulin-Like Receptors Maintain Unique Antigen-Presenting Properties of Circulating Myeloid Dendritic Cells in HIV-1-Infected Elite Controllers.” Journal of Virology 84 (18): 9463-9471

Kawashima, Y., K. Pfafferott, J. Frater, P. Matthews, R. Payne, M. Addo, H. Gatanaga, et al. 2009. “Adaptation of HIV-1 to Human Leukocyte Antigen Class I.” Nature 458 (7238): 641-645

Mahalanabis, M., P. Jayaraman, T. Miura, F. Pereyra, E. M. Chester, B. Richardson, B. Walker, and N. L. Haigwood. 2009. “Continuous Viral Escape and Selection by Autologous Neutralizing Antibodies in Drug-Naïve Human Immunodeficiency Virus Controllers.” Journal of Virology 83 (2): 662-672

Matthews, P. C., A. Prendergast, A. Leslie, H. Crawford, R. Payne, C. Rousseau, M. Rolland, et al. 2008. “Central Role of Reverting Mutations in HLA Associations with Human Immunodeficiency Virus Set Point.” Journal of Virology 82 (17): 8548-8559

Pereyra, F., S. Palmer, T. Miura, B. L. Block, A. Wiegand, A. C. Rothchild, B. Baker, et al. 2009. “Persistent Low-Level Viremia in HIV-1 Elite Controllers and Relationship to Immunologic Parameters.” Journal of Infectious Diseases 200 (6): 984-990

Virgin, H. W. and B. D. Walker. 2010. “Immunology and the Elusive AIDS Vaccine.” Nature 464 (7286): 224-231

Salk Institute Leads $21M HIV Research Focusing on Early Immune System Responses

NEW YORK (GenomeWeb News) – A new research consortium led by the Salk Institute of Biological Studies and the Sanford-Burnham Medical Research Institute will use a $21 million grant from the National Institutes of Health to conduct systems biology-based studies of the earliest immune system responses to HIV infection.

The multidisciplinary research effort will include DNA sequencing, expression analysis, RNAi analysis, mass spectrometry, and other efforts aimed at discovering the cellular protein mechanisms that are the first line of defense against HIV.

Along with Salk and Sanford-Burnham, the research program will fund research at the University of California, San Francisco; Mount Sinai School of Medicine; the University of California, San Diego; Northwestern University; and the University of Pennsylvania.

“The events that occur immediately after exposure to HIV, which determines the ability of the virus to establish infection and ultimately shape the course of the disease, are very poorly understood,” Sumit Chanda, an adjunct professor at the Salk Institute, said in statement.

“This grant funds a multi-center consortium that will integrate cutting edge technologies in systems biology and next-generation sequencing, with world-leading expertise in immunology and virology to decode and model the early molecular events that occur after HIV enters the body,” Chanda added. “These projects will be fundamental towards the development of safe and effective HIV vaccines, as well as novel preventative therapies for HIV.”

The research will include next-generation sequencing focused on identifying relevant polymorphisms at Northwestern University, microarray expression analysis at Burnham and Mount Sinai, high-throughput affinity purification mass-spec approaches at UCSF, and large-scale RNAi analysis projects at Sanford-Burnham, Chanda told GenomeWeb Daily News in an e-mail.

ScienceDirect Publishes Quarterly Top 25 “Most Downloaded” Reports

ScienceDirect (Elsevier) publishes quarterly lists of the most highly downloaded papers.  ScienceDirect, Elsevier’s full text platform, offers access to over 2000 peer reviewed science/technology/medical journals.   You may subscribe to custom lists of “hottest” articles by choosing subject categories or individual journal titles.    Sign up to receive email notices at “TOP25.” Congratulations to Paul Bieniasz and other members of the Aaron Diamond research team on being among the latest “TOP25” in Biochemistry, Genetics and Molecular Biology for their article in CELL on the activity of tetherin in HIV-1 infection.

HIV-1 Rapid Immune System Damage In Early Stages of Infection

ScienceDaily (July 14, 2009) — The virus that causes AIDS is classified as a lentivirus, a word derived from the Latin prefix, “lenti-,” meaning “slow.” But new research from the NIAID-funded Center for HIV/AIDS Vaccine Immunology suggests that HIV-1 is anything but – moving at breathtaking speed in destroying and dysregulating the body’s gut-based B-cell antibody-producing system.    Read about the research conducted at Duke University.

Lemur Genome May Provide HIV Insights

ScienceDaily (Dec. 2, 2008) — The genome of a lemur from Madagascar may provide new understanding how HIV-like viruses coevolved with primates.  The discovery published online in the Proceedings of the National Academy of Sciences, could provide insight into why non-human primates don’t get AIDS and lead to treatments for humans.  Rob Gifford, PhD, researcher in infectious diseases and geographical medicine is lead author of the new study.   Gifford searched primate species DNA for strings of nucleotides that matched the modern lentivirus genome and found one lurking in the DNA of the tiny gray mouse lemur.  Gifford’s work on lentivirus-primate interaction might open doors for HIV/AIDS research.

Enhanced expression of T-cell receptors in CD8 T cells increases HIV-1 binding 450-fold

Investigators at the University of Pennsylvania School of Medicine and Cardiff University, UK have engineered T-cells which are able to recognize HIV-1 strains that typically fall under the radar.  In the November 9, 2008 advanced online Nature Medicine publication of Control of HIV-1 immune espcape by CD8 T cells expressing enhanced T-cell receptor, researchers describe T cells that bonded more strongly and in a more aggressive manner so that fewer T cells were required to control HIV-1 infection.

It is hoped that clinical trials with the engineered T-cells will begin in 2009 to establish safety.  If laboratory results can be translated effectively in the clinic, a powerful “disguise detection” therapy may emerge which could treat early-stage HIV-1 infections. 

(Extracts from ScienceDaily, November 10, 2008 and Nature Medicine published online November 9, 2008; doi:10.1038/nm.1779)

Antibody Fragment Powerful HIV Inhibitor

Previous research has shown that reducing antibodies to the smallest independently functional fragment effectively extends their utility as therapeutic agents.   Researchers at NCI identified the domain fragment, m36, as having the ability to very strongly inhibit multiple HIV strains.  It also provides new insights into how the virus invades the call and neutralizes the immune system.   This research was published online October 20, 2008.  Chen, W, Zhu Z, Feng Y, Dimitrov DS. Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizers. Proceedings of the National Academy of Sciences.