Scholar Profiles
Ali
Al-Agely
2006 - 2007 University Scholar
Mentor: Max Teplitski
College of Liberal Arts and Sciences
"In the experience thus far with my mentor, I have begun to learn many useful techniques, skills and methods. Prior to this opportunity, I was under the assumption that doing research was ridden with monotony. However, as I have become more involved in performing my research, I understand this field is, in fact, dynamic. A new challenge frequently appears compelling me to become deeply involved in my work"
This sophomore biochemistry major is wasting no time getting ready for life post-undergraduate degree. He holds particular interests in medical related subjects, such as neuroscience, nutrition and genetics. His main focus at the moment is the phenomenon of antibiotic resistance. Some of Ali’s academic accolades include the W.W. Massey Sr. Presidential Scholarship, a nomination into the National Society of Collegiate Scholars and memberships in Phi Eta Sigma and Delta Epsilon Iota academic honor societies. In his spare time, Ali enjoys reading, football, basketball, stay abreast of current events and playing guitar.
Research Description:
Identifying Compounds that Inhibit BarA/UvrY Cascade in E. coli
Biofilms are complex, multi-cellular structures consisting of microorganisms in a rich, protective environment. Forming on locations such as the inner walls of water treatment pipes to surgical devices, biofilms are of modern industrial, medical, environmental and economical importance.
In Escherichia coli, a γ-proteobacteria, orthologs of the two-component regulatory system BarA/UvrY are central to the regulation of genes required for virulence, motility and biofilm formation. Upon perception of a currently unidentified signal, the BarA sensor kinase autophosphorylates and then phosphorylates its cognate response regulator UvrY. The downstream effects of the BarA/UvrY are mediated by the Csr post-transcriptional regulatory system. In this system, the CsrA protein directly binds to messages and either promotes or inhibits the translation of the bound mRNA. The activity of the CsrA protein is antagonized by two small regulatory RNAs, csrB and csrC. The csrB promoter is directly bound by the phosphorylated UvrY, which effects transcription of the csrB gene. Because BarA/UvrY-regulated genes are required for cellular attachment and virulence in biofilms, the objective of this research is to identify compounds that specifically block this regulatory cascade.
In order to identify signals that disrupt BarA/UvrY-mediated gene regulation, I will construct and screen a metagenomic library for the clones that inhibit or prematurely activate the csrB-lacZY reporter in E. coli. To construct the metagenomic library, I will extract total DNA from several environmental mixed-species biofilms. The metagenomic DNA will then be sheared and ligated into a suitable expression vector. The resulting library will then be transformed into the chemically-competent E. coli cells which carry the csrB-lacZY reporter. Transformations will be recovered on a medium containing appropriate antibiotics (to select for the transformed cells) and X-gal (colorimetric substrate for LacZY). Normally, csrB-lacZY appears blue when treated with X-gal. From observations, any metagenomic clone that affects the expression of the csrB-lacZ reporter will be identified and further investigated in the barA, uvrY or csrA mutant backgrounds.
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