Discipline: Biological Sciences
Thomas Hahn - University of Arkansas at Little Rock
Co-Author(s): Thomas Hahn1,2, Richard Segall4, Helen Benes2 and Fusheng Teng*3 1Dept. of Information Science, University of Arkansas at Little Rock, Little Rock, AR 72204 2University of Arkansas for Medical Sciences, Little Rock, AR, 72205 3*Dept. of Applied Science, University of Arkansas at Little Rock, Little Rock, AR, 72204 4Dept. of Computer and Information Technology, Arkansas State University, Jonesboro, AR, 72467
Purpose: The objective is to understand how sterol transport is affected by caloric restriction (CR) and aging. Sterol synthesis generally increases as cells age. Yet, despite this increase, the sterol content of selected organelle membranes, such as lysosomal membranes, declines with age and adversely affects cellular functions. We are interested in a better understanding of changes in sterol transport to membranes of vacuoles (the yeast counterparts of mammalian lysosomes) in response to anti-aging and pro-aging manipulations. Methods: The protein Erg6 is involved in sterol synthesis, while Atg15 is associated with autophagy, a process for degradation of damaged materials by vacuoles (or lysosomes). Wild Type (WT) cells have been found to live longer with CR, while the lifespan of the erg6Δ and atg15Δ mutants is significantly shortened by CR. In a comparison of erg6Δ and atg15Δ mutants with WT during CR, we looked for changes in expression of genes that could be involved in lifespan extending mechanisms triggered by CR. We used microarray data to determine the responses to different combinations of mutations and to food availability and to examine differential expression of those genes. We constructed “heat maps” to identify the relevant genes and determined their roles in biological pathways, using this information to draw relevant gene interaction networks. Results: In a previously published study, Kaeberlein et al. screened 570 knockout mutants for lifespan changes (1). More detailed results are shown in Figure 1 and 2. Conclusions: Identifying changes in gene expression that maintain the sterol proportion and asymmetry across the vacuolar membrane in yeast could be the basis for novel drug development aimed at altering the expression of gene homologues in humans, such that adverse age-associated changes in the human lysosomal membrane could be postponed or even reversed. We have identified a number of gene candidates that can be easily studied in yeast for drug design.ERN Abstract with figures.docx
Funder Acknowledgement(s): This project was supported by the Arkansas INBRE program, with grants from the National Center for Research Resources - NCRR (P20RR016460) and the National Institute of General Medical Sciences - NIGMS (P20 GM103429) from the National Institutes of Health.
Faculty Advisor: Richard Segall, RSegall@AState.edu
Role: I did all the genomics analysis. I did everything except for the wet-lab work, which I can no longer do since I became legally blind. I got the microarray gene expression data from a CD-ROM. From then onward its all my work.