# Lineage-Specific Mechanisms of Cell Cycle Timing Control

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $50,979

## Abstract

Project Summary
Decades of studying animal development and in vitro human cell culture have produced many observed tight
correlations between the duration of a cell’s cycle and its identity or the fates of its progeny. These links
represent a unique opportunity to understand the regulatory relationships between genetic programs of cell
fate and the regulation of the cell cycle, both central questions in the study of development, tissue
homeostasis, regeneration, and proliferative disorders such as cancer. The nematode Caenorhabditis elegans
has been a powerful model in which to study the regulation of cell fate and cell cycle control owing to its
genetic tractability, transparent body and embryo, and stereotyped cell lineage. Like most nematodes, C.
elegans exhibits eutely or a fixed number of somatic cells in each individual of the same sex. Cell fate in the
wild-type animal can thus be determined solely on the basis of its lineage history, for which we have developed
extensive tools and approaches for automated reconstruction via 3D timelapse microscopy. Using C. elegans
and genetic perturbations that result in transformations of cell fate with its lineage, in combination with
automated lineage tracing and spatial transcriptomics approaches, we will investigate the mechanisms by
which cell fate influences the duration of a stem cell’s cell cycle as well as the mechanisms by which the
duration of a cell cycle can influence cell fate.
The work described in this proposal represents a novel approach to considering these links, enabled by our
development of lineage tracing technologies and quantitative approaches to discovering structure in cell
lineages. Building on this expertise, as well as our imaging resources and collaborations with other tools
developers, theorists, and developmental biologists, we will continue to advance the state-of-the-art in lineage-
resolved studies of metazoan development. In particular, using our advances in deep learning techniques to
enable label-free automated lineage tracing in non-model species in which transgenesis remains impossible or
difficult, we will leverage an evolutionary approach to understanding the design principles of gene networks
that drive cell fate decisions and control cell cycle progression in the early embryo. Over the next five years we
will complete detailed characterizations of co-dependencies between cell cycle timing and cell fate in the C.
elegans embryo, create a molecular atlas of cell fate and cell cycle regulation in wild type and mutant C.
elegans where cell fate patterning is perturbed, and complete the reconstruction and quantitative analysis of
the embryonic lineages of S. stercoralis, P. pacificus, and C. angaria. In the long term, we plan to extend our
molecular analyses to these species as well, beginning with C. angaria as an attractive model for studying the
evolution of cell fate control networks and their interactions with regulators of the cell cycle. These insights will
...

## Key facts

- **NIH application ID:** 11037680
- **Project number:** 3R35GM151199-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Pavak Kirit Shah
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $50,979
- **Award type:** 3
- **Project period:** 2023-09-30 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037680

## Citation

> US National Institutes of Health, RePORTER application 11037680, Lineage-Specific Mechanisms of Cell Cycle Timing Control (3R35GM151199-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11037680. Licensed CC0.

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