John A. T. Young
B.Sc., Biochemistry, University of Dundee, United Kingdom
Ph.D., Human Genetics, University College London and Imperial Cancer Research Fund, United Kingdom
Postdoctoral Fellow, University of California San Francisco
John A. T. Young, a Professor in the Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, studies the cell biology of virus infection and anthrax intoxication. His laboratory is identifying and characterizing cellular factors that contribute to the early steps of infection by HIV and other retroviruses, influenza virus, and filoviruses such as Ebola virus. These studies are giving novel insights into virus-host interactions and are suggesting new therapeutic strategies for combating virus infection. The Young laboratory has also identified both known cellular receptors for anthrax toxin. Current research in the lab is aimed at understanding how these receptors, along with other cellular factors, regulate anthrax toxin entry into cells. Soluble versions of a cellular receptor are also being developed as receptor decoys to efficiently neutralize anthrax toxin.
"A major goal of our work is to reveal how host cell proteins
either contribute to or defend against infection by important
human microbial pathogens, such as HIV, influenza virus, Ebola
virus and the bacterium that causes anthrax. Knowledge of the
roles played by this cellular machinery provides new insights
into the cell biology of microbial infections and could suggest
new broad-spectrum antimicrobial approaches."
A major focus of Young's work is on the HIV
virus. HIV/AIDS continues to be a serious
global problem. The virus can remain "hidden"
in a latent form in infected individuals
for years, even after long-term suppression
with highly active antiretroviral therapy.
Moreover, viral drug resistance represents a
formidable problem, creating an urgent need
for new classes of antiretrovirals.
HIV begins its assault by injecting its core,
which contains single-stranded RNA, into
a host cell. Once inside, the viral RNA is
converted into double-stranded DNA—a
process known as reverse transcription—and
the original viral RNA is degraded. Another
enzyme, integrase, mediates the final step
of the genome conversion, where the viral
double-stranded DNA slips into the host's
DNA, allowing it to take advantage of the
host cell's genetic machinery to replicate and
propagate itself. During these early steps of
infection, the virus relies heavily on its host
cell to lend a helping hand, which makes it
particularly vulnerable to antivirals and host
To identify cellular processes that either
facilitate or defend against HIV-1 infection,
Young and his collaborators use systems
biology approaches to investigate the roles
played by individual genes in the genome
of host cells. These experiments have
uncovered ZASC1, a new regulator of virus
gene expression. They have also revealed
that sulfonation—a type of chemical modification—
regulates viral gene expression. A
number of cellular factors they have identified
restrict HIV infection, some of which
play known roles in innate immunity, one of
the body's defense mechanisms that protect
against microbial infections. In addition, virus
countermeasures of these host defenses
are being identified. Young anticipates that
these discoveries will open up new avenues
for the development of drugs that specifically
interfere with HIV replication.
Awards and Honors
- Eli Lilly and Company Research Award in Microbiology and Immunology
- Fellow, American Academy of Microbiology
Bruce, J.W., Ahlquist P., and Young, J.A.T. (2008) The host cell sulfonation pathway contributes to retroviral infection at a step coincident with provirus establishment. PLoS Pathogens November; 4(11): e1000207.
König, R., Zhou, Y., Elleder, D., Diamond, T.L., Bonamy, G. M.C., Irelan, J.T., Chiang, C., Tu, B.P., De Jesus, P.D., Lilley, C.E., Seidel, S., Opaluch, A.M., Caldwell, J.S., Weitzman, M.D., Kuhen, K.L., Bandyopadhyay, S., Ideker, T., Orth, A.P., Miraglia, L.J., Bushman, F.D., Young, J.A.T., Chanda, S.K. (2008) Global analysis of host-pathogen interactions that regulate early stage HIV-1 Replication. Cell. Volume 135, Issue 1, 49-60.
Scobie, H.M., Marlett, J.M., Thomas, D., Rainey, G.J.A., Lacy, D.B., Collier, R.J. and Young, J.A.T. 2007. Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation. PLoS ONE. 2:e329.
Scobie H.M., Wigelsworth D.J., Marlett J.M., Thomas D., Rainey, G.J.A., Lacy D.B., Manchester, M. and Young J.A.T. 2006. Anthrax Toxin Receptor 2-Dependent Lethal Toxin Killing in vivo. PLoS Pathogens. 2:e111.
Rainey, G.J., Wigelsworth, D.J., Ryan, P.L., Scobie, H.M., Collier, R.J. and Young, J.A.T. 2005. Receptor- specific Requirements for Anthrax Toxin Delivery into Cells. Proc. Natl. Acad. Sci. U.S.A. 102(37):13278-13283.
Narayan, S. and Young, J.A.T. 2004. Reconstitution of Retroviral Fusion and Uncoating in a Cell-free System. Proc. Natl. Acad. Sci. U.S.A. 101:7721-7726.
Scobie, H.M., Rainey, G.J.A., Bradley, K.A. and Young, J.A.T. 2003. Human Capillary Morphogenesis Protein 2 Functions as an Anthrax Toxin Receptor. Proc. Natl. Acad. Sci. U.S.A. 100:5170-5174.
Bradley, K.A., Mogridge, J., Mourez, M., Collier, R.J. and Young, J.A.T. 2001. Identification of the Cellular Receptor for Anthrax Toxin. Nature. 414:225-229.
Mothes, W., Boerger A.L., Narayan, S., Cunningham, J.M. and Young, J.A.T. 2000. Retroviral Entry Mediated by Receptor Priming and Low pH Triggering of an Envelope Glycoprotein. Cell. 103:679-689.
Salk News Releases
- Salk Institute and Sanford-Burnham study selected most-cited paper in Molecular Biology & Genetics, January 4, 2011
- NIH awards $21 million grant to study early stages of HIV-1 infection, August 12, 2010
- Nomis Foundation's $6.5 million gift supports research in Immunobiology; Salk ends fundraising year above $31-million mark, June 28, 2010
- Novel regulatory step during HIV replication, November 13, 2008
- What HIV Needs, October 2, 2008
- Innovative dual action anthrax vaccine-antitoxin combination, October 5, 2007
- Unexpected features of anthrax toxin may lead to new types of therapies, August 29, 2005
- Several minute intermediate stage in virus-cell fusion discovered; possible window of opportunity for drug development, June 8, 2005
- A New View of HIV, June 7, 2004
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