The EpiLab approach

01
Engineering

The EpiLab designs and builds novel molecular tools, including complex, cell-type-specific constructs that push the limits of standard molecular biology. If the tool doesn't exist, we make it.

02
Biology

We deploy those tools to dissect the molecular mechanisms of epigenetics and epitranscriptomics, asking how gene regulation at the RNA and chromatin level drives brain function.

03
Psychology

We then ask what happens behaviorally. Using rodent models of memory and stress, we connect molecular changes to the cognitive and affective outcomes that matter for human health.

Walters Lab

Dr. Brandon Walters | Epitranscriptomics & Memory

m6A & Memory Formation

N6-methyladenosine (m6A) is the most abundant internal modification on messenger RNA in the brain. These marks are dynamic: written, erased, and read by dedicated proteins in response to cellular activity. This makes m6A well-positioned to serve as a fast, reversible signal during learning.

The Walters Lab investigates how the brain deploys m6A during memory consolidation. Most of our stereotaxic surgeries target the hippocampus, using behavioral tasks including contextual fear conditioning, novel object recognition, and novel object-in-place to probe what animals remember and what they forget.

Stress, Adversity & Depression

Not all of memory is about remembering where you left your keys. The Walters Lab has recently expanded into studying how stress-induced epitranscriptomic changes may contribute to depression-related outcomes.

In collaboration with the McCormick Lab, we use the Social Instability Stress during Adolescence (SIS) model to study how chronic stress during a critical developmental window drives depression-related outcomes in adulthood. We are also developing a maternal separation model in mice in-house, building on prior rat-based work to test whether the paradigm translates across species.

Core Methodology

DART-seq: Reading the m6A Landscape

1
The Target m6A sits within a canonical consensus sequence, always adjacent to a cytosine (C)
2
The Reader The YTH domain naturally binds m6A. The Meyer Lab fused mutagen APOBEC1 to it
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The Mutation APOBEC1 converts the neighboring C→U, leaving a permanent, sequenceable mark
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Expanding DART-seq The Walters Lab modifies DART-seq to expand what it can measure, going beyond m6A localization alone

DART-seq was developed by the Meyer Lab. The Walters Lab builds on this foundation with modified constructs designed to answer questions the original method was not built to ask.

Collaborative Highlight

Engineering a Cre-Inducible sgRNA for Cell-Type-Specific Knockout

One of the more technically demanding constructs produced by the Walters Lab was a Cre-inducible sgRNA built for a collaboration with the Josselyn Lab. The challenge: the U6 promoter that drives sgRNA expression has strict sequence requirements, and there are no introns or stop codons available as conventional "blockers." Solving this required a non-standard molecular engineering approach. This construct enabled cell-type-specific CB1 receptor knockout in PV+ interneurons of the amygdala, contributing to a publication in Cell.

Behavioral Models

Contextual Fear Conditioning

Our standard assay for hippocampal-dependent associative memory.

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Novel Object Recognition

Tests recognition memory and hippocampal function in rodents.

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Novel Object-in-Place

Spatial variant of NOR, sensitive to hippocampal and cortical contributions.

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Social Instability Stress

Adolescent stress model developed with the McCormick Lab to study depression-related outcomes.

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Maternal Separation

In-house model under development. Extending a validated rat paradigm to mice.

Zovkic Lab

Dr. Iva Zovkic | Epigenetics, Histone Variants & Memory

Zovkic Lab Research: Coming Soon

Dr. Zovkic's lab investigates histone variants and their role in memory and Alzheimer's disease. A full research overview is being prepared and will be added shortly.

Techniques & Approaches

DART-seq AAV / Lentiviral Engineering CRISPR / sgRNA Design Knockdown & Overexpression Stereotaxic Surgery Next-Gen Sequencing (NGS) Cell Culture Molecular Biology Rodent Behavior Contextual Fear Conditioning Immunohistochemistry