Graduation Year
2025
Document Type
Campus Only Senior Thesis
Degree Name
Bachelor of Arts
Department
Biology
Reader 1
Danae Schulz
Reader 2
Daniel Stoeble
Terms of Use & License Information
Abstract
Trypanosoma brucei, the unicellular, protozoan parasite that causes both Human and Animal African Trypanosomiasis, cycles between a bloodstream form in mammals and a procyclic form in the insect vector. In the mammalian bloodstream, T. brucei evades the host immune system by varying expression of Variant Surface Glycoproteins (VSGs) on the cell surface. In flies, the cell surface is instead coated in one, invariant protein called procyclin. Procyclin is coded for by a set of GPEET and EP genes. The mechanism by which transcription of these EP genes is initiated during differentiation from the bloodstream to procyclic form is not yet well understood. Our research group previously investigated the role of chromatin interacting proteins in regulating the expression of life cycle stage specific genes. Ashby et al. A de novo increase in occupancy of a bromodomain reader protein, Bdf3, near the EP1 gene locus in parasites induced to differentiate to the procyclic form (Ashby et al., 2022). We hypothesized that chromatin remodeling near the EP1 locus by the histone acetyltransferase enzyme, HAT2, and the protein subunit of the Nu4 Histone Acetyltransferase complex, EAF6, facilitates Bdf3 binding and subsequent EP1 transcription during differentiation. To test this, T. brucei strains were modified to include FLAG tagged HAT2 and EAF6 at the endogenous loci. We further modified these strains to allow for a doxycycline inducible knock down of HAT2 or EAF6. We demonstrate that the knockdown of target proteins was induced in drug treated bloodstream parasites. However, we found that target proteins were not knocked down in drug treated parasites induced to differentiate to the procyclic form. Experiments to support or refute our hypothesis about the role of HAT2 and EAF6 in initiating transcription of EP1 could therefore not be completed. Further studies may provide insight into the mechanisms of transcriptional activation as parasites transition between diverse host environments.
Recommended Citation
Enright, Brecken, "Investigating the Role of HAT2 and EAF6 proteins in initiating transcription of insect stage proteins in African Trypanosomes" (2025). Scripps Senior Theses. 2634.
https://scholarship.claremont.edu/scripps_theses/2634
This thesis is restricted to the Claremont Colleges current faculty, students, and staff.
