# Dynamic architecture and function of microtubule networks

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2024 · $435,875

## Abstract

Summary
Microtubules (MTs) are dynamic biopolymers, which serve as major highways for intracellular transport. MT
networks are critical for cell physiology, and their disturbance underlies many human diseases. My laboratory
studies global mechanisms allowing MTs to perfectly attribute to specific cellular functions.
MT-dependent transport arranges multiple cell components at the same time. To address these complex
requirements, MT geometry, molecular motor affinity, and/or MT association with to other cell components are
tightly regulated. MT network geometry changes depending on the sites of new MT outgrowth (the MT-organizing
centers, or MTOCs), local stabilization/disassembly of MTs, and MT anchoring to other structures. Furthermore,
the affinity of individual MTs to molecular motors can be modulated to affect intracellular transport. Finally, MTs
can scaffold proteins or be cross-linked with other cytoskeletal components. All those mechanisms that tailor MT
organization to distinct cell functions can respond dynamically to cell-signaling inputs and the physiological
context. Together, molecular regulation and functional specialization of MT networks comprise a global field in
basic cell biology with numerous unanswered questions. My research program’s long-term goals include
defining: how interphase MT networks are built and regulated; specific mechanisms tailoring MT
biochemistry and geometry to specific cellular needs; the methods whereby MTs collaborate with other
cellular systems to build intracellular space; and, how MTs switch their functional loads between distinct
tasks to arrange integral cell architecture under changing signaling conditions.
Since April 2018, the NIGMS MIRA funding mechanism has been an invaluable resource allowing us to explore
these basic, fundamental biological problems. We have published several central advances toward our global
and interactive goals. Among other findings, we brought a new mechanistic understanding of Golgi-derived MT
networks (GDMTs, which were identified in our prior studies); described novel, surprising functions for MT-
associated proteins (MAPs) tau, CLASP2, and CAMSAP2; utilized collaborations with experts in computational
modeling for deep understanding of MT functions in secretory trafficking and actin cytoskeleton dynamics; and,
discovered a previously overlooked, physiologically important Golgi complex behavior in the cell cycle.
In the next five years, I will extend mechanistic and functional insights in two broad directions of my program’s
extant NIGMS-funded research. (I) We will determine how the versatility of MT functions is tuned by
multifunctional MAPs, focusing on (a) secretory trafficking through the Golgi axis and (b) the organization of the
actin cytoskeleton. Initial studies will evaluate the roles of MT regulators CLASPs and a MT-stabilizing tumor
suppressor RASSF1A. (II) We will expand our studies of MT-dependent Golgi positioning to dissect (a) molecular
mechanisms dri...

## Key facts

- **NIH application ID:** 10842308
- **Project number:** 5R35GM127098-07
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Irina Kaverina
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $435,875
- **Award type:** 5
- **Project period:** 2018-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842308

## Citation

> US National Institutes of Health, RePORTER application 10842308, Dynamic architecture and function of microtubule networks (5R35GM127098-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10842308. Licensed CC0.

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