GUDIPATI LAB
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Our laboratory investigates the functions of evolutionarily conserved and clinically relevant DPPIV family proteases. Through a series of focused research projects, we aim to uncover how these proteases regulate protein stability and gene expression, and to explore their potential roles in neurological disorders and other human diseases
Development of Specific and potent inhibitors of C. elegans DPF-3
Aditya Trivedi aims to develop selective inhibitors of the Caenorhabditis elegans protease DPF-3, a key regulator of small RNA-mediated silencing, while minimizing inhibition of human DPPIV family proteases. He uses a dual-assay screening strategy utilizing both biochemical and organismal approaches. First, candidate compounds are screened for enzyme inhibition using recombinant DPF-3 and a fluorogenic substrate. Second, the selected compounds are tested in vivo using a C. elegans strain carrying a fluorescent reporter (Pzc15.3::ZC15.3-Wrm Scarlet::ZC15.3 3’UTR), which enables direct visualization of DPF-3 inhibition via red fluorescence triggered by de-silencing of the ZC15.3 transposon. This whole-organism biosensor provides a rapid and quantitative readout of target engagement.
Discovering a New Guardian of Genome Stability
Ankit Roy’s research focuses on the mechanisms by which cells protect their genomes from transposable elements, the “jumping genes” that pose constant threats to genomic integrity. Our recent work identifies picd-1, a previously uncharacterized protein, as an essential factor in maintaining genome stability in the C. elegans germline. When picd-1 is absent, animals show progressive germline decline and sterility, particularly at elevated temperatures. This temperature-sensitive phenotype suggests that picd-1 function becomes critical under environmental stress. PICD-1 regulates components of small RNA pathways, systems that cells use to silence transposable elements and protect genome integrity across generations. The conservation of PICD-1's protein domains from nematodes to humans hints that similar mechanisms may operate across species, potentially offering insights into fertility, genome stability, and stress responses in higher organisms.