Investigation of Potential Corresponding Human Proteins in Naegleria Amoeba

Abstract

Record ID: 228

Award: Excellence in Research Mentoring

Program Affiliation: UCBA Honors

Student Major: Pre-Medical Labratory Science

Project Advisor: Yoshi Odaka

Abstract: When humans contract Primary Amebic Meningoencephalitis (PAM) from freshwater amoeba Naegleria fowleri, death is almost always imminent. From 1962 to 2021, only 2.60% of people in the United States survived the infection, in part because there is no established mechanism to manage or cure PAM. In quest of potential drug targets to treat this disease, we have conducted a protein comparison search and identified CFTR (cystic fibrosis transmembrane conductance regulator)-like and BRCA2 (breast cancer susceptibility gene 2)-like genes in N. fowleri and Naegleria gruberi, a species of amoeba that does not lead to disease. In humans, a mutation in the CFTR protein results in cystic fibrosis, while a mutation in BRCA2 increases the risk of developing different cancers including breast and ovarian cancer. Due to safety reasons, N. gruberi was used for further experiments. Protein sequence comparisons revealed that human CFTR has 29.53% and 31.35% identities with the CFTR-like protein in N. gruberi and N. fowleri, respectively, and human BRCA2, on the other hand, has 29.66% and 27.27% identities with N. gruberi and N. fowleri, respectively. With this level of variation between the proteins in humans and the amoeba, eventual targeting of these gene products may have fewer adverse effects in humans. Importantly, our other data show the CFTR-like protein in both Naegleria species is phosphorylated at a different site from the human CFTR. Currently, we are investigating different gene expressions of CFTR-like and BRCA2-like gene transcripts in N. gruberi by a method called quantitative PCR.