# Super-resolution Microscopy Study of Molecular Transport Mechanisms

> **NIH NIH R35** · TEMPLE UNIV OF THE COMMONWEALTH · 2024 · $485,882

## Abstract

PROJECT SUMMARY
Our laboratory has developed unique tools that have enabled further progress towards
understanding molecular transport mechanisms involving three sub-cellular organelles in
eukaryotic cells: the nucleus, cytoplasm, and primary cilium. Macromolecular trafficking among
these compartments is suggested to be gated by two unique mechanisms. One is the nuclear
pore complex (NPC) embedded in the nuclear envelope that mediates bidirectional trafficking of
proteins and RNAs between the cytoplasm and the nucleus; the other is the transition zone (TZ)
located at the base of primary cilium that regulates the entry of membrane and cytosolic proteins
into the cilium.
Progress is intimately linked to technical improvements in biophysical research putting us in the
unique position to elucidate the fast kinetics and 3D transport routes of macromolecules as they
transport through the sub-micrometer NPC or TZ in live cells. In the first four years of the current
five-year MIRA grant, we have completed the development of single-point edge-excitation sub-
diffraction (SPEED) microscopy and successfully applied the new method to solve several critical
questions pertaining to nuclear transport and cytoplasmic-ciliary transport. We have included our
major findings in thirty manuscripts and published them in prestigious scientific journals such as
Nature Structural & Molecular Biology, Nature Communications, Protein Science, and Nature
Protocols.
Currently we are highly motivated to work on the following new research topics: 1) Development
of a new optical imaging system termed enhanced photon microscopy aiming at doubling photon
collection efficiency from fluorophores, which will significantly improve optical resolutions when
integrated with epifluorescence microscopy, laser scanning confocal microscopy, SPEED
microscopy and other super-resolution microscopy; 2) Mapping the spatial organization of
dynamic disordered protein motifs in the NPC to distinguish between, and advance upon, FG-
organizational models; and 3) Understanding the gating mechanism for the cytoplasmic-ciliary
transport of membrane proteins. In summary, during the next funding period of the MIRA grant,
we will continue to develop new microscopy imaging techniques and solve long-standing
unanswered questions in both nucleocytoplasmic and cytoplasm-cilium transport mechanisms.

## Key facts

- **NIH application ID:** 10868618
- **Project number:** 5R35GM122552-08
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Weidong Yang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $485,882
- **Award type:** 5
- **Project period:** 2017-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868618

## Citation

> US National Institutes of Health, RePORTER application 10868618, Super-resolution Microscopy Study of Molecular Transport Mechanisms (5R35GM122552-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10868618. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*