UT Arlington Bio-Analytical Chemist Receives Academic Research Enhancement Award

A bio-analytical chemist exploring proteins, their structures and functions by using cutting-edge analytical instrumentation called mass spectrometry has received an Academic Research Enhancement Award from the National Institutes of Health. The $354,749 in funding will help in identifying host-defense protein interactions networks caused by environmental and external agents.

Saiful Chowdhury, assistant professor in the Department of Chemistry and Biochemistry, University of Texas at Arlington, is the principal investigator on the project. He is developing a mass spectrometry-based chemical cross-linking technology that will provide information on large-scale protein signaling networks in their natural biological conditions.

"Proteins reside inside and outside of the cells, and when we open the cells, most of the interaction information that can help us to better understand disease processes gets lost," Chowdhury said. "Current biochemical methods are not very efficient to analyze system-level or large-scale protein interaction networks. Through innovative analytical techniques, and by chemical cross-linking of proteins before cell analysis, we can overcome current limitations."

Chowdhury will conduct his studies at UT Arlington's Shimadzu Center for Advanced Analytical Chemistry, which has several high-performance mass spectrometers. He will also utilize a new mass spectrometer with advance protein sequencing features being installed in his laboratory soon.

A mass spectrometer is an instrument that can identify protein or peptide (small pieces of protein) sequences by fragmenting them into small pieces and analyzing their masses. Chowdhury's lab is developing crosslinkers, which contain a specific mass that will be released during mass spectrometry analysis.

"It is like a mass barcode in this probe, which will help to find protein interaction sites from millions of mass spectrometry data," he said. "This will enable us to find the specific fragment markers in the mass spectrometry data so cross-linked proteins can be identified clearly in a high-throughput automated manner."

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The goal will be to develop a mass spectrometry-based chemical cross-linking technology to help recognize protein-to-protein interactions unambiguously and reduce data complexity of large-scale studies. His laboratory is also developing associated software tools for the research with the help of UT Arlington computer science students.

Chowdhury added that the anticipated application of the technology will be to identify the protein signaling networks involved in environmental diseases, such as sepsis and asthma, as well as cancer. The research will help scientists find new drugs targeted to disrupt protein interaction networks in the disease processes.

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James Grover, interim dean of the UT Arlington College of Science, called Chowdhury's project, "a wonderful example of the innovative work that is being done in UT Arlington's world-class facilities."

In January, Chowdhury received a $391,000 grant from The University of Texas System Board of Regents to purchase a new mass spectrometer. The equipment will be used by him as part of a UT System-wide Proteomics Core Facility Network that arises from several UT campuses, including UT Arlington.

"The main objective of the network is to make available high quality proteomics technologies and expertise to all researchers and trainees across UT System's nine universities and six health institutions," UT System Vice Chancellor for Research and Innovation Patricia D. Hurn said in a statement.

The University of Texas Medical Branch at Galveston, which was awarded $5.7 million for the initiative, will direct administrative functions of the network. Other participating institutions include UT Austin, UT MD Anderson Cancer Center, UT Health Northeast (formerly UT Health Science Center at Tyler), UT Southwestern Medical Center in Dallas and UT Health Science Center at San Antonio.

In addition to the NIH and UT System grants, Chowdhury's group recently detailed a novel proteomics technology that analyzes lipid modification in proteins. Their study, "Mass Spectrometry Cleavable Strategy for Identification and Differentiation of Prenylated Peptides," is published in the current journal Analytical Chemistry.

The modifications, which are called prenylation, attach lipid side-chains in the proteins. They have been associated with 90 percent of pancreatic and colon cancers as well as progeria, a genetic disease that causes the premature aging of children.

"Most clinical trials to block this change in a widely known cancer-causing protein did not work," Chowdhury said. "Due to the absence of effective methods, large-scale identification of proteins that contained this modification was not possible in native biological conditions."

The method that Chowdhury's group reported not only identified the modification sites, but can also distinguish the variation of the modification in a single experimental set-up by mass spectrometry technology. Chowdhury thinks the method will significantly contribute to advancing the understanding of cancer mechanism, its treatment and diagnosis.

Source-Medindia