Mari Gachechiladze

Program: Neurosciences

Current advisor: Joseph D. Dougherty, PhD

Undergraduate university: Georgetown University, 2017

Enrollment year: 2019

Research summary
Epigenetic susceptibility factors for seizures in mice

Transcription factors (TFs) are responsible for utilizing the genome to enact patterns of gene expression that define a wide variety of functional states in living systems including development, differentiation, and stress. TFs achieve this precise regulation by binding to specific sites in the genome. There are several methods available for profiling this binding, including antibody-based methods such as ChIP-seq and CUT/RUN, as well as TF-fusion protein-based methods such as DamID and Calling Cards. While many of these methods are capable of describing the current state of a system, they cannot describe how that state came to be. Calling Card technology uses a transposase and a TF-transposon reporter fusion to leave records of TF binding events, allowing us to integrate TF binding over time and connect the binding events to a later phenotype of interest.

One such phenotype is seizure severity in response to GABA antagonist pentylenetetrazol (PTZ). Previous work demonstrated that when genetically identical wild-type mice housed in similar conditions encounter the same dose of PTZ at age P28, some have mild seizures, whereas others have severe seizures. If there are individual epigenetic differences in the mice that alter their susceptibility to PTZ-induced seizures, the Calling Card system should be able to detect them. Using Syn1-Cre driven transposase, preliminary experiments have showed differential gene expression in both known seizure-related genes and others between mice with mild and severe seizure phenotypes. Further validation will determine if this differential expression is a real biological phenomenon and provide a proof-of-concept for the power of Calling Card technology to define epigenetic susceptibility.

Graduate publications
Gachechiladze MA, Dougherty JD. 2024 Neurodevelopmental Genetic Associations Across the Translational Space-Time Continuum. Biol Psychiatry, 95(9):825-27. PMCID:

Yen A, Mateusiak C, Sarafinovska S, Gachechiladze MA, Guo J, Chen X, Moudgil A, Cammack AJ, Hoisington-Lopez J, Crosby M, Brent MR, Mitra RD, Dougherty JD. 2023 Calling Cards: A Customizable Platform to Longitudinally Record Protein-DNA Interactions Over Time in Cells and Tissues. Curr Protoc, 3(9)::e883. PMCID: PMC10627244