Candidate Name: Kaitlin Elizabeth Klotz
Program: Biology
Committee Chairs: Dr. Kausik Chakrabarti​​​​​​​
Committee Members: Dr. Sarah Stellwagen, Dr. Junya Tomida, Dr. Andrew Truman, Dr. Shan Yan, Dr. Rebekah Rogers
Abstract:

Telomeres are repetitive DNA sequences that protect chromosome ends through repeated cell divisions. They are synthesized and maintained by telomerase, a ribonucleoprotein complex composed of Telomerase RNA (TR), which provides the template for telomere synthesis, and Telomerase Reverse Transcriptase (TERT), the catalytic enzyme subunit. Although telomerase has been extensively studied in humans, far less is known about its regulation in parasitic organisms such as Trypanosoma brucei, the causative agent of African sleeping sickness. This parasite depends on continuous proliferation and sustained telomerase activity for survival.

This study investigates how the structure of T. brucei telomerase RNA (TbTR) contributes to telomerase assembly and function. We hypothesized that discrete structural domains within TbTR are required to maintain its global architecture, promote interaction with TERT, and support enzymatic activity. To test this, we performed RNA structural probing using SHAPE chemistry to visualize TbTR structure in wild-type parasites and in mutant cell lines lacking discrete RNA domains. We then characterized structural alterations resulting from these deletions. Additionally, RNA sequencing was used to compare transcriptomes in the presence and absence of telomerase activity, revealing how telomerase disruption modulates global gene expression.