January 2009


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Biosciences Graduate Students <[log in to unmask]>
Wed, 21 Jan 2009 13:54:42 -0500
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"Diane St. Germain" <[log in to unmask]>
George Mason University
To: "Dr. Charles Bailey" <[log in to unmask]>, Myung Chul Chung <[log in to unmask]>, Li Dong <[log in to unmask]>, Suhua Han <[log in to unmask]>, Serguei Popov <[log in to unmask]>, Taissia Popova <[log in to unmask]>, Anne K Taylor <[log in to unmask]>, Monique Van Hoek <[log in to unmask]>, Clint B Smith <[log in to unmask]>, Shelley C Jorgensen <[log in to unmask]>, Aarthi Narayanan <[log in to unmask]>, "Dr.Nanda Gudderra" <[log in to unmask]>, Lance Liotta <[log in to unmask]>, Emanuel Petricoin <[log in to unmask]>, Mark M Ross <[log in to unmask]>, Weidong Zhou <[log in to unmask]>, Joseph Henry Hix <[log in to unmask]>, Jessica Kidd <[log in to unmask]>, Jim Willett <[log in to unmask]>, Nathan Manes <[log in to unmask]>, Calvin B Carpenter <[log in to unmask]>, Rong Fu <[log in to unmask]>, Jennifer L Guernsey <[log in to unmask]>, Biosciences Graduate Students <[log in to unmask]>, Biology Graduate Students <[log in to unmask]>, [log in to unmask] cc: Kathy Powell <[log in to unmask]>, Peter A Becker <[log in to unmask]>
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*A Reminder --

*Dissertation Defense Announcement:
To:  The George Mason University Community*

*Yian Kim Tan
PhD Biodefense Candidate
*Date:   Thursday January 22, 2008
Time:   9:00 a.m.
Place:  George Mason University, Prince William campus
	     Discovery Hall Auditorium
Dissertation Director:  Dr. Aiguo Wu, M.D., Defense Threat Reduction Agency
Dissertation Chair: Dr. Charles Bailey, Ph.D., National Center for Biodefense and Infectious Diseases

Title: Novel Functions of Anthrax Lethal Toxin*


Bacillus anthracis is a gram positive spore-forming bacterium that can 
cause cutaneous, gastrointestinal or inhalational anthrax in many 
animals and humans. Vegetative B. anthracis generates two essential 
virulence factors: the anthrax lethal toxin and the poly-g-D glutamic 
acid capsule. The primary virulence factor is a secreted zinc-dependent 
metalloprotease toxin known as lethal factor (LF), which is introduced 
into the cytosol by protective antigen (PA) through its receptors on the 
cells. LF exerts its toxic effect through the disruption of 
mitogen-activated protein kinase kinase (MAPKK) signaling pathway, which 
is essential in mounting an efficient and prompt immune response against 
the invading pathogen. LF also mediates the destruction of host cells 
through either necrotic cell death or apoptosis pathway depending upon 
the genetic background of the cell types.

Autophagy is an evolutionary conserved intracellular process whereby 
cells break down long-lived proteins and organelles. Accumulating 
evidences suggest increasing physiological significance of autophagy in 
pathogenesis of infectious diseases. In addition to the myriad of 
effects that LT exerts on different cell types, we describe herein a 
novel effect of LT-induced autophagy on mammalian cells. Several 
autophagy biochemical markers including LC3-II conversion, increased 
punctuate distribution of GFP-LC3 and development of acidic vesicular 
organelles (AVO) were detected in cells treated with LT. Analysis of 
individual LT component revealed a moderate increase in LC3-II 
conversion for protective antigen-treated cells, whereas the LC3-II 
level in lethal factor-treated cells remained unchanged. Moreover, our 
preliminary findings suggest a protective role of autophagy in LT 
intoxication as indicated by accelerated cell death when autophagy was 
inhibited.  Separately, LT was also shown to induce harmful levels of 
reactive oxygen species (ROS) in immune cells although antioxidant 
appeared to have some protective effects against its damaging effects. 
In addition, chemotaxis analysis revealed that LT not only fail to 
elicit chemokines production in immune cells but also suppressed the 
chemokines-inducing properties of lipopolysaccharides (LPS) and 
bacterial cell wall (CW). The wide array of effects that LT exerts on 
various immune cells reflects the intricacies of the intoxication 
mechanisms. These findings enhance our understanding of anthrax 
pathogenesis and may prove to be relevant to the development of a more 
effective countermeasure against anthrax.


*A copy of the dissertation is on reserve in the Johnson Center Library, 
Fairfax campus.  The doctoral project will not be read at the meeting, 
but should be read in advance. *

*All members of the George Mason University community are invited to