Gerard C. L. Wong

Bio: Gerard C. L. Wong is an academic researcher from University of California, Los Angeles. The author has contributed to research in topics: Antimicrobial peptides & Biofilm. The author has an hindex of 51, co-authored 173 publications receiving 8831 citations. Previous affiliations of Gerard C. L. Wong include California Institute of Technology & University of California, Berkeley.

The Pel Polysaccharide Can Serve a Structural and Protective Role in the Biofilm Matrix of Pseudomonas aeruginosa

Abstract: Bacterial extracellular polysaccharides are a key constituent of the extracellular matrix material of biofilms. Pseudomonas aeruginosa is a model organism for biofilm studies and produces three extracellular polysaccharides that have been implicated in biofilm development, alginate, Psl and Pel. Significant work has been conducted on the roles of alginate and Psl in biofilm development, however we know little regarding Pel. In this study, we demonstrate that Pel can serve two functions in biofilms. Using a novel assay involving optical tweezers, we demonstrate that Pel is crucial for maintaining cell-to-cell interactions in a PA14 biofilm, serving as a primary structural scaffold for the community. Deletion of pelB resulted in a severe biofilm deficiency. Interestingly, this effect is strain-specific. Loss of Pel production in the laboratory strain PAO1 resulted in no difference in attachment or biofilm development; instead Psl proved to be the primary structural polysaccharide for biofilm maturity. Furthermore, we demonstrate that Pel plays a second role by enhancing resistance to aminoglycoside antibiotics. This protection occurs only in biofilm populations. We show that expression of the pel gene cluster and PelF protein levels are enhanced during biofilm growth compared to liquid cultures. Thus, we propose that Pel is capable of playing both a structural and a protective role in P. aeruginosa biofilms.

Reversible Cell‐Specific Drug Delivery with Aptamer‐Functionalized Liposomes

Abstract: cis-Diamminedichloroplatinum(II) (cisplatin) is a potent chemotherapeutic agent for the treatment of a broad range of cancerous tumors. 2] Despite its excellent antitumor efficacy, the major drawbacks of cisplatin include its lack of tumor specificity and severe side effects. In addition, certain tumor-cell types develop resistance to cisplatin from exposure to the drug. Strategies that allow the delivery of cisplatin specifically to tumor cells are highly desirable. Several strategies have been reported for the delivery of cisplatin specifically to tumor sites, the most common of which is to use antibody (Ab) recognition against different cell-surface targets. The binding of Abs to the cell-membrane receptors triggers receptor-mediated endocytosis, with the result of improved therapeutic efficacy. Despite this success, the use of Abs as cell-specific homing agents poses significant challenges. Ab conjugations are difficult to control and typically show poor site specificity for the conjugation and inconsistent binding affinity. The antibody-based drugdelivery system also tends to be immunogenic, so it requires extra humanization steps, which make it more difficult for clinical application. Nucleic acid based aptamers provide excellent alternatives to antibodies as cell-specific agents. They are singlestranded oligonucleotides identified through an in vitro selection process, termed system evolution of ligands by exponential enrichment (SELEX), to bind the target molecules selectively. 12] Many aptamers identified by SELEX have nearly identical binding affinity and specificity to those of Abs. Aptamers are much easier to prepare and to scale up. They are generally considered nonimmunogenic and can be gradually degraded by nucleases and cleared from the blood to cause minimal system toxicity. Functionalizations of aptamers to facilitate site-specific conjugation are also straightforward. Thus, aptamers are promising targeting ligands and have been used in targeted drug-delivery systems, most of which are block-copolymer nanoparticles. Although these new nanotechnology-based platforms look promising, the clinical benefit of nanoparticles for targeted cancer therapy is yet to be demonstrated. Liposomes are by far the most successful drug-delivery systems; a number of liposome-based systems have been approved by the US Food and Drug Administration for disease treatment in the clinic. Liposomes have been shown to increase the plasma residence time of aptamers. Previous efforts on liposomal drug delivery have focused on developing long-circulating liposomes that target cancerous tumor tissues through the enhanced permeation and retention (EPR) effect, 34] a passive targeting mechanism. However, cancer targeting entirely based on EPR still has undesirable systemic side effects and suboptimal antitumor efficacy: clinical studies of a cisplatin-containing liposome showed only poor to moderate therapeutic efficacy. 38] Delivery vehicles with active tumor-targeting capability could, in principle, improve this significantly. Personalized chemotherapy is an unmet challenge in cancer treatment. Despite the existence of rough empirical dosage guidelines, the individual patient response can deviate strongly from average behavior. This problem is especially acute for chemotherapy agents, for which drug overdosage can have severe consequences. At present, once an initial dosage is administered, the side effects and drug effectiveness can no longer be modulated if there are no “antidotes” to the treatment. However, the discovery of good antidotes or neutralizers for each individual drug molecule is not an easy task, if even practical. Moreover, there are no known ways to “multiplex” different antidotes to control complex treatment profiles with multiple drugs. We report here the controlled formulation of aptamerconjugated, cisplatin-encapsulating multifunctional liposomes. Cancer-cell-specific targeting and drug delivery are demonstrated by using this delivery platform. Furthermore, we also show for the first time that a complementary DNA (cDNA) of the aptamer can function as an antidote to disrupt [*] R. Tong, A. Mishra, Prof. G. C. L. Wong, Prof. J. Cheng, Prof. Y. Lu Department of Materials Science and Engineering University of Illinois at Urbana-Champaign 1304 W. Green Street, Urbana, IL 61801 (USA) Fax: (+ 1)217-333-2736 E-mail: gclwong@illinois.edu jianjunc@illinois.edu Homepage: http://www.matse.illinois.edu/faculty/wong/profile.html http://www.matse.illinois.edu/faculty/cheng/profile.html Dr. Z. Cao, W. Xu, Prof. Y. Lu Department of Chemistry University of Illinois at Urbana-Champaign 600 S. Mathews Avenue, Urbana, IL 61801 (USA) Fax: (+ 1)217-244-3186 E-mail: yi-lu@illinois.eduyi-lu@illinois.edu Homepage: http://www.chemistry.illinois.edu/faculty/Yi_Lu.html [] Z.C. and R.T. contributed equally to this work.

Living in the matrix: assembly and control of Vibrio cholerae biofilms

Abstract: Nearly all bacteria form biofilms as a strategy for survival and persistence. Biofilms are associated with biotic and abiotic surfaces and are composed of aggregates of cells that are encased by a self-produced or acquired extracellular matrix. Vibrio cholerae has been studied as a model organism for understanding biofilm formation in environmental pathogens, as it spends much of its life cycle outside of the human host in the aquatic environment. Given the important role of biofilm formation in the V. cholerae life cycle, the molecular mechanisms underlying this process and the signals that trigger biofilm assembly or dispersal have been areas of intense investigation over the past 20 years. In this Review, we discuss V. cholerae surface attachment, various matrix components and the regulatory networks controlling biofilm formation.

Psl trails guide exploration and microcolony formation in Pseudomonas aeruginosa biofilms.

Abstract: Cell-tracking experiments and simulations show that the Psl exopolysaccharide deposited by Pseudomonas aeruginosa guides the surface motility of subsequent cells that encounter the Psl trails, generating a ‘rich-get-richer’ effect that leads to microcolony formation. How bacteria self-organize into microcolonies — the first step towards forming biofilms — is poorly understood. Here Gerard Wong and colleagues use a massively parallel cell-tracking algorithm to extract the motility history of every cell during colonization of a new surface. This system reveals that Pseudomonas aeruginosa deposits a trail of exopolysaccharide which influences the motility of any other cells that subsequently encounter it, generating a positive feedback that directs the cells to form a microcolony. The positive feedback observed here is analagous to the 'rich-get-richer' power law observed in wealth distribution. Bacterial biofilms are surface-associated, multicellular, morphologically complex microbial communities1,2,3,4,5,6,7. Biofilm-forming bacteria such as the opportunistic pathogen Pseudomonas aeruginosa are phenotypically distinct from their free-swimming, planktonic counterparts7,8,9,10. Much work has focused on factors affecting surface adhesion, and it is known that P. aeruginosa secretes the Psl exopolysaccharide, which promotes surface attachment by acting as ‘molecular glue’11,12,13,14,15. However, how individual surface-attached bacteria self-organize into microcolonies, the first step in communal biofilm organization, is not well understood. Here we identify a new role for Psl in early biofilm development using a massively parallel cell-tracking algorithm to extract the motility history of every cell on a newly colonized surface16. By combining this technique with fluorescent Psl staining and computer simulations, we show that P. aeruginosa deposits a trail of Psl as it moves on a surface, which influences the surface motility of subsequent cells that encounter these trails and thus generates positive feedback. Both experiments and simulations indicate that the web of secreted Psl controls the distribution of surface visit frequencies, which can be approximated by a power law. This Pareto-type17 behaviour indicates that the bacterial community self-organizes in a manner analogous to a capitalist economic system18, a ‘rich-get-richer’ mechanism of Psl accumulation that results in a small number of ‘elite’ cells becoming extremely enriched in communally produced Psl. Using engineered strains with inducible Psl production, we show that local Psl concentrations determine post-division cell fates and that high local Psl concentrations ultimately allow elite cells to serve as the founding population for initial microcolony development.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

X-Ray Diffraction

Abstract: Interpretation of X-ray Powder Diffraction Patterns . By H. Lipson and H. Steeple. Pp. viii + 335 + 3 plates. (Mac-millan: London; St Martins Press: New York, May 1970.) £4.