Uncovering the Role of Histone Acetylation in Tetrabromobisphenol A-induced Developmental Toxicity during Zygotic Genome Activation - Project abstract: The overall goal of this diversity supplement is to provide Mr. Rojas with a niche research area in addition to the parent R03 and facilitate his career development within biomedical sciences. While the parent grant focuses on the impacts of Tetrabromobisphenol A (TBBPA) on maternal-to- zygotic transition and histone acetylation, the supplement focuses on the role of naa10- an N- terminal (Nt) acetyltransferase (NAT) gene that is potentially a crucial regulator of the newly synthesized proteome by stabilizing them through Nt acetylation. Our hypothesis for the supplement grant is that the developmental toxicity observed in TBBPA-exposed embryos is partly driven by inhibition of naa10, resulting in inhibited Nt- acetylation of peptides. Based on this premise, the additional aims described differ from the parent grant as it is focused on a different (but linked) mechanism of TBBPA-induced toxicity during the same exposure regime. Within the supplement, aim 1 will determine the role of naa10 in TBBPA-induced developmental delays through naa10 mRNA injections, phenotyping and qPCR. In aim 2, Mr. Rojas will profile naa10- induced effects on Nt-acetylation by cloning naa10, purifying protein and conduct Nt-acetylation assay. Overall, within this supplement, I will mentor Mr. Rojas to achieve training in several molecular biology strategies such as cloning, microinjection, protein purification and biomolecular assays. Coupled with his training in -omics and data integration within the parent grant, this supplement will provide Mr. Rojas an exciting opportunity to lead an independent project in molecular toxicology and learn molecular techniques. In addition, it will also provide him with several opportunities to be proficient in scientific writing, networking, conference presentations that will be valuable for his professional development and career goals.
