# Origins of Cell Geometry

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $648,271

## Abstract

Abstract
Cells are highly complex living nanomachines with beautiful structures of great precision.
This is true not only for free living organisms like ciliates or radiolarians, but also for cells
inside the human body. These complicated structures are directly linked to the
physiological functions of cells, and alterations in cell geometry are a hallmark of many
disease states. Yet in most cases we have almost no information about how cells
determine their geometry at the level of organelle size and shape. Thus, understanding
the origins of cell geometry remains a fundamental unsolved problem in cell biology.
Part of the challenge is that cell geometry involves multiple spatial scales ranging from
molecules up to the whole cell. Spanning this gap between scales requires us to go
beyond traditional molecular biology approaches and bring in methods from physics and
engineering. For this reason my proposal is based on an integrated combination of
approaches, using several different model organisms and cell types to address the
origins of cell geometry at several different size scales. At the level of single organelles,
I will continue to probe the mechanism of flagellar length control as a paradigm for
organelle size regulation, with a focus on using quantitative methods to test a series of
mechanistic models for how a cell might be able to sense the length of its flagellum. At
the same time, we will apply the lessons and approaches that we have developed for
thinking about flagella to examine size control and geometry of other cellular organelles,
singly and in combination. By considering multiple organelles at the same time, we can
learn how to view cell geometry at a more integrative level. At a larger scale, we will
continue our development of the classic model organism, Stentor coeruleus, as a
genomic model system for analyzing global cell morphogenesis and regeneration.
Using Stentor, we intend to pursue the two linked questions of how a cell knows that is
geometry has been perturbed, and how it directs the re-assembly of a correct cell
geometry, both questions that have general significance to all cell types but which are
particularly easy to study in Stentor. Our proposed work is unified by the focus on a
single question – where does geometry come from inside a cell. We will use different
model systems to address different aspects of this question, but in all cases we will take
an interdisciplinary approach that combines tools of genetics, genomics, microscopy,
image analysis, and mathematical modeling.

## Key facts

- **NIH application ID:** 9859408
- **Project number:** 5R35GM130327-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Wallace Marshall
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $648,271
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859408

## Citation

> US National Institutes of Health, RePORTER application 9859408, Origins of Cell Geometry (5R35GM130327-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9859408. Licensed CC0.

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