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EIU Graduate School

Robert and Kathryn Augustine
Distinguished Master's Thesis Award Winner

Jessica Derham, Master of Science in Biological Sciences, earned EIU's top research honor for her master's thesis titled, Determination of the Functional Significance of Glutamate Carboxypeptidase II in Folate Metabolism in Caenorhabditis elegans.

Gopal Periyannan, Ph.D., Professor of Biochemistry and Britto Nathan, Ph.D., Professor, Biological Sciences, served as faculty mentors.

The award is named for, and supported by, former dean of the Graduate School, Dr. Robert Augustine, and his wife, Kathy, an EIU alumna.

Thesis Abstract

Glutamate Carboxypeptidase II (GCPII) is a transmembrane metalloprotease produced in many human tissues and many other organisms. One Jessica Derhamfunction of GCPII is the transformation of dietary folate to allow its absorption across the intestinal membrane. Folate is a cofactor in the biosynthesis of DNA, RNA, amino acids, and in many other cellular growth and reproduction pathways. Folate cannot be synthesized in higher organisms therefore must be taken through diet and the specific roles of GCPII in this process remain underexplored. The goal of this research is to characterize the functional roles of GCPII in folate metabolism and the overall effect of GCPII on the reproductive and physiological biochemistry using the model organism, Caenorhabditis elegans. C. elegans GCPII is produced as three paralogs: gcp-2.1, gcp-2.2, and gcp-2.3, which are similar in structure to the five paralogs of human GCPII. The main hypothesis is that each GCPII paralog has unique, tissue-specific functional role/s. Sulfamethoxazole mediated folate-limited E. coli OP50, the food source for C. elegans, was fed to the wild type, gcp-2.1, gcp-2.2, and gcp-2.3 null mutant strains. Alternatively, the same C. elegans strains were fed the sulfamethoxazole treated OP50 that was supplemented with the folate derivative tetrahydrofolate. Under these conditions, both brood size and longevity were measured to assess the effect of GCPII on folate metabolism and folate mediated reproductive and physiological effects. Additionally, HPLC based folate derivative assessment of the food source was conducted to identify different folate forms. Tetrahydrofolate, dihydrofolate, and folinic acid were present in untreated OP50 but none were detected in SMX treated OP50. Altogether, the results showed that median longevity of the GCPII paralogs increased relative to the wild type and tetrahydrofolate supplementation restored reproduction in all strains at different levels.

Full thesis may be accessed at Booth Library's The Keep

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Eastern Illinois University
600 Lincoln Avenue Charleston, IL 61920
Fax: 217-581-6020

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