# Molecular mechanisms in the mammalian cell nucleus

> **NIH NIH R35** · RICE UNIVERSITY · 2024 · $344,031

## Abstract

Abstract/Project Summary
My research group strives to gain detailed information about cellular nanoscale structures, dynamics, and
molecular mechanisms by designing and applying innovative and versatile single-molecule imaging tools,
labeling schemes, and analysis algorithms. The goal of our research is to improve our understanding of cellular
function and pathogenesis by answering biophysical questions related to normal function, laminopathies,
ciliopathies, cancers, and other diseases. One of our primary research interests and long-term goals is
understanding the mammalian cell nucleus, including its related and anchored proteins, its chromatin
organization and dynamics, and how they relate to gene regulation in healthy cells and during disease
progression. In this proposal, we will build upon our expertise in fluorescence single-molecule tracking and super-
resolution imaging, engineered point spread functions (PSFs) for 3D detection of single molecules with tens of
nanometer precision, light sheet illumination for reduced out-of-focus background fluorescence, photobleaching,
and photodamage during whole live-cell imaging, our recently developed dCas9-based nanobody array labeling
approaches for long-term tracking of chromatin dynamics with excellent spatiotemporal resolution, and our
recently developed light sheet-compatible microfluidic system for precise control of the extracellular environment.
We will implement and expand these innovations to address a range of biophysical questions related to molecular
mechanisms behind cellular function in healthy cells and during disease progression, including how the dynamics
of chromatin organization affect gene expression and what the molecular mechanisms are that underlie the
premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS). To achieve our goals, we will pursue
the following main thrusts: (1) develop and implement approaches for labeling and live-cell 3D tracking of specific
chromosomal loci pairs, such as enhancer-promoter (EP) pairs, and gene expression during adjustable
extracellular conditions. These measurements will yield novel data with unprecedented spatiotemporal resolution
on enhancer and promoter dynamics, EP separation, contact frequency, and contact duration, and establish how
these parameters relate to transcriptional output. This will enable us to uncover fundamental physical
mechanisms of gene regulation and will set the stage for future research on interaction kinetics of various
regulatory elements implicated in chromatin reorganization and gene regulation. (2) Define the molecular
interactions of the mutated protein progerin in HGPS and map how its nanoscale spatial distribution and
interactions with other proteins and with chromatin are affected by treatment with available and novel therapies.
This thrust will be of great significance for human health by evaluating the molecular mechanisms of
pathogenesis and treatment strategies for HGPS and the results may ...

## Key facts

- **NIH application ID:** 10940774
- **Project number:** 1R35GM155365-01
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Anna Karin Eva Gustavsson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $344,031
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940774

## Citation

> US National Institutes of Health, RePORTER application 10940774, Molecular mechanisms in the mammalian cell nucleus (1R35GM155365-01). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10940774. Licensed CC0.

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