Telomeres are the DNA-protein complexes found at the ends of eukaryotic linear chromosomes. Telomeres pose a unique challenge to eukaryotic cells as they are unable to fully replicate their DNA all the way to the ends. If this problem is not resolved, cells would lose DNA after every cell division and telomeres would shorten. Over time this leads to significant telomere loss and genome instability. This issue is resolved by the ribonucleoprotein telomerase. Telomerase is the enzyme responsible for maintaining telomere length. The telomerase enzyme is composed of two main components: the telomerase reverse transcriptase protein, which catalyzes the extension of telomeric ends, and the telomerase RNA that provides the template for telomere synthesis. The telomerase RNA also forms a large structural scaffold upon which many accessory proteins can bind to form the complete telomerase holoenzyme. These interacting proteins and regulatory mechanisms are well studied in human, yeast and Tetrahymena systems. Telomerase interacting proteins and regulatory mechanisms have not been well studied in several ancient eukaryotes including clinically relevant human parasites like Trypanosoma brucei (T. brucei). T. brucei is a protozoan parasite that causes African sleeping sickness in humans. T. brucei, like many eukaryotic microbial pathogens, relies on constant high levels of telomerase activity to sustain the high proliferative capacity necessary to establish a successful infection in its human host. The aim of this dissertation is to highlight novel mechanisms of telomerase regulation in the ancient eukaryote, T. brucei. Chapter 1 is a published review synthesizing what is known about telomerase structure and regulation across model eukaryotes with emerging views in parasitic protozoa. Chapter 2 describes a published study where we identified the first global interactome of telomerase in the bloodstream form T.brucei parasites using telomerase reverse transcriptase (TERT) as a bait in a mass spectrometry-based proteomics approach. Chapter 3 is an unpublished study where we identified the global interactome of the procyclic form T.brucei TERT and PTMs on semi-purified T. brucei telomerase using a mass spectrometry-based mapping approach. Chapter 4 describes an unpublished study where we studied the role of different structural domains in the T. brucei telomerase RNA and their relationship with the above interactors in telomerase RNA stability and telomerase catalytic activity.