Research Interests:
- Type III secretion system(T3SS) of Pseudomonas aeruginosa.
- Regulation of the T3SS
- T3SS mediated host cell apoptosis
- Applications
- Membrane permeability and multidrug resistance.
- Regulation of membrane
- permeability
- Drug discovery
- Sensitive detection of pathogens, toxins and chemicals.
- Technology development
- Device fabrication
Pseudomonas aeruginosa causes a wide range of infections, from minor skin infections to serious and sometimes life-threatening complications. P. aeruginosa is a causative agent of systemic infections in immunocompromised patients such as those receiving chemotherapy, elderly patients and burn victims. In special groups of patients, P. aeruginosa can also cause localized infections, particularly in the lungs of cystic fibrosis patients and corneals of certain contact lens users.
Type III secretion system (T3SS) is encoded by various animal and plant pathogens. It encodes over 30 proteins that assemble into a “needle” complex designed to deliver bacterial proteins directly into the cytoplasmic compartment of eukaryotic cells. In animal pathogens, the principle function of T3SS is to deliver anti-host-virulence-determinants into mammalian cells, thus evading host immune attack.
(i) Regulation. The T3SS of P. aeruginosa responds to various environmental signals such as low calcium, direct contact with mammalian cells and various environmental stresses. We are interested in understanding the regulatory mechanism by which the T3SS genes are regulated during various stages of host infections.
(ii) T3SS induced apoptosis..
There are four known effector molecules that are secreted by the T3SS of P. aeruginosa, including ExoS, ExoT, ExoY and ExoU. The ExoS has an ADP-ribosyltransferase activity which triggers efficient host cell death through apoptosis. We intend to understand the mechanism by which the translocated bacterial protein (ExoS) triggers host cell apoptosis and elucidate relevant apoptotic pathways.
(iii)Applications. The T3SS can be modified for the secretion/injection of various proteins of interests for the purpose of protein production, vaccine delivery, cancer therapy and many others.
Membrane permeability is actively controlled by bacteria, responding to growth environment. A two-component regulatory system has been identified in P. aeruginosa which regulates the bacterial membrane permeability. We intend to understand the molecular details of the membrane permeability control and identify chemicals that increase membrane permeability. We propose to combat and limit the development of antibiotic resistance by combined use of permeability-enhancing chemicals with antibiotics.
Sensitive detection technologies and devices are being developed for sensitive detection of various pathogens, toxins and chemicals. These are collaborative efforts with chemists and engineers.
Recent Publications: (2005-2008)
Wu, W., and S. Jin. (2005) PtrB of
Pseudomonas aeruginosa
suppresses type III secretion system under the stress of DNA damage.
J Bacteriology 187:
6058-6068.
Kim, J., K. Ahn, S. Min, J, Jia, U. Ha, W. Lian an
S. Jin. (2005) Factors triggering type III secretion in
Pseudomonas aeruginosa.
Microbiology 151:
3575-3587.
Wu, W., Y. Song, S. Jin and S. Chen. (2005) An
interactive map of regulatory networks of
Pseudomonas aeruginosa
genome. Proc Second Annual
RECOMB Satellite Workshop on Regulatory Genomics.
Qian, M., C. K. Fredrickson, S. Jin and Z. H. Fan.
(2005) Toxin detection by miniaturized
in vitro protein
expression array. Analy. Chem.
77: 5494-5500.
Song, Y., W. Wu, S. Jin, S. Chen. 2006. An
intelligent system for constructing and visualizing interactive
regulatory networks. REDCOM Proc 35: 4544-49.
Alaoui-El-Azher, M., J. Jia, and S. Jin. (2006)
Molecular ordering of Pseudomonas aeruginosa induced-apoptosis: Critical involvement of
the mitochondrial death pathway in a Fas system independent manner.
Cell Microbiol 8: 326-338.
Jia, J., and S. Jin. (2006) ExoS of
Pseudomonas aeruginosa is
sufficient to cause apoptosis.
Infect Immun 74: 6557-70.
Qian, M., C. K. Fredrickson, W. Lian, S. Jin and
H. Fan (2006) Ricin detection by signal amplification in a
miniaturized device. Analy
Chemistry 78: 7659-64.
Fan, Z. H.; Mei, Q.; Simon, A.; Fredrickson, C.
K.; Lian, W.; Jin, S. (2006) Protein synthesis in a plastic device
for toxin detection. Soc Chem & Micro-Nano Sys
1: 1026-1028.
Yang, H., Z. Shan, J. Kim, W. Wu, W. Lian, L. Zeng,
L. Xing and S. Jin. (2007) Regulatory role of PopN and its
interacting partners on type III secretion of
Pseudomonas aeruginosa.
J Bacteriology 189:
2599-609.
Brandt, S., S. Shafikhani, P. Balachandran, S.
Jin, R. Hartig, W. König, J. Engel and S Backert. (2007) Distinct
activities of Pseudomonas
aeruginosa ExoS and ExoT toxins on host actin cytoskeletal
responses induced by the
Helicobacter pylori CagA protein.
FEMS Immun Microbiol 50:
190-205.
Bai, F., Y.
Li, H. Xu, H. Xia, T. Yin, H. Yao, L. Zhang, X. Zhang, Y. Bai, S.
Jin, M. Qiao (2007) Identification and functional characterization
of PA2950, a novel gene involved in swimming motility of Pseudomonas
aeruginosa. Gene. 401:
19-27.
Guo, M., S.
Jin, C. Hew and S. Pan. (2007) Recruitment of conjugative DNA
transfer substrate to Agrobacterium type IV secretion apparatus.
Proc. Natl. Acad Sci. USA. 104: 20019-24.
Poon, K., E. L. Westman, E. Vinogradov, S. Jin
and J. Lam (2008)
Functional characterization of MigA and WapR: rhamnosyltransferases
involved in outer core oligosaccharide biosynthesis of
Pseudomonas aeruginosa. Infect and Immun 190: 1857-65.
Galle, M., M. Haegman, H. Yang, S. Jin, P. Schotte and R. Beyaert.
(2008) The Pseudomonas
aeruginosa type III secretion system plays a dual role in the
regulation of caspase-1 mediated IL-1β processing.
J Cell Mol Med 12:1767-76.
Luo, Q., and
S. Jin (2008) Molecular derterminants in regulation of the
Pseudomonas aeruginosa
type III secretion system.
Acta Micro Sin (in press).
Ha, U., J-H. Lim,
W. Wu, S. Jin and J-D. Li (2008) MKP1 is required for MUC5AC mucin
induction by S. pneumoniae
pneumolysin via inhibition of PAK4-JNK signaling pathway.
J Biol Chem 283:30624-31.
Luo, Y., S.
Jin, A. Xu, D. Wu (2008) Cloning, expression, purification and
functional characterization of recombinant human Interlukin-7.
Pro. Exp. & Pur. 63:1-4.
Wang,
F., J.
Xiao, L. Pan, M. Yang, G. Zhang, S. Jin and Jun Yu. (2008) A
systemic survey of mini-proteins in bacteria and archaea.
PLosOne (submitted).
Martino,
A.T., C. Mueller, S. Braag, M. Campbell-Thompson, S. Jin,
T. R. Flotte. (2008) Treating an N-glycosylation abnormality in
murine airways with a deficiency in the cystic fibrosis
transmembrane conductance regulator (CFTR) protein reduces
Pseudomonas aeruginosa colonization; a hallmark symptom of
cystic fibrosis. Laboratory
Investigation (submitted).
