# Intracellular transport and organelle biology at the nanoscale: A multidimensional super-resolution approach

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $441,375

## Abstract

Project Summary
My research takes a unique approach in which the development of next-generation microscopy methods
progresses in parallel with fundamental discoveries in cell biology. On the method-development front, besides
earlier success in achieving sub-10 nm resolution for super-resolution microscopy, my recent work has
pioneered the concept of multidimensional and multifunctional super-resolution microscopy, in which
intracellular functional parameters, including local chemical polarity, pH, diffusivity, and protein activity, are
mapped out at nanometer resolution and single-molecule sensitivity. Empowered by such capabilities, my lab
has been highly successful in unveiling hidden subcellular structures and processes, as well as their underlying
biophysical rules, for diverse systems ranging from the mammalian cytoskeleton, intracellular transport,
organelle morphology and biogenesis, to membrane biology. Our future research continues to push forward the
synergy between method development and biological discoveries. Major directions include charge-modulated
protein interactions and effects on diffusion inside the organelle lumen, superdiffusion and subdiffusion in the
living cell, organelle pH dynamics and role in protein trafficking, and the structure and physical properties of the
ER exit site in relationship with the biogenesis of transport carriers. Moreover, by integrating super-resolution
microscopy with FIB-SEM, we will obtain holistic pictures of the unusually thin tubular organelles we recently
discovered and further substantiate their functions and biogenesis. Separately, we are developing a new tool,
single-molecule electrophoresis microscopy, to quantify protein charge states at the super-resolution level.
Together, through the continued development of empowering microscopy tools and their tactical application to
fundamental biological questions, we will continue shifting the paradigms of how we understand the complex,
dynamic behavior of the cell.

## Key facts

- **NIH application ID:** 10929300
- **Project number:** 5R35GM149349-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Ke Xu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,375
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929300

## Citation

> US National Institutes of Health, RePORTER application 10929300, Intracellular transport and organelle biology at the nanoscale: A multidimensional super-resolution approach (5R35GM149349-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10929300. Licensed CC0.

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