# Determining the cell fate programs of mammalian retina development

> **NIH NIH F31** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2023 · $47,694

## Abstract

Project Summary/Abstract
 The overarching goal of this proposal is to understand how the stereotypical structure of retina forms
during embryonic development. Towards this goal, this proposal seeks to develop novel molecular recording
technologies that allow the reconstruction of lineage history based on endpoint measurements. This method
leverages genome editing techniques to stochastically create heritable mutations within synthetic barcode
arrays that accumulate edits over time. Because readout of these arrays is compatible with spatial
transcriptomics technologies, these methods when combined will allow the simultaneous capturing of
transcriptional cell state, lineage relationships, and spatial position of single cells within retina tissue. The
resulting lineage tree datasets will then be analyzed using a novel statistical tool termed Lineage Motif
Analysis, a computational approach to identify all significantly over- or under-represented cellular patterns. This
approach systematically enumerates all possible arrangements of observed fates on progressively larger
subtrees and then compares their frequencies to those expected in a null model based on uncorrelated cell
fate between cell divisions. Lineage trees will reveal how birth-order of cell types is regulated on the clonal
level and lineage motifs will reveal the extent to which lineage in the retina is stochastic or preprogrammed.
Furthermore, lineage motifs represent direct insight into the “rules” that govern how the retina forms during
development, and provide a way to describe how such “rules” change in different contexts like disease or
pharmacological perturbation. The datasets and analysis proposed here will inform the development of new
therapeutic strategies for regenerative medicine to treat retinal diseases that lead to blindness.
 My training program outlined here will equip me with the necessary tools and knowledge to (1) carry out
the aims of this proposal and gain novel biological understanding, and (2) advance me towards my career goal
of leading a research team focused on studying the fundamental principles that underlie embryonic
development and disease progression. I will work with Dr. Long Cai, a pioneer in spatial transcriptomics, to
learn imaging and image processing techniques, as well as Dr. Carlos Lois, an expert in neurobiology, to learn
mouse manipulation and surgical procedures. Dr. Elowitz and I will meet regularly to discuss my research
progress, writing plans for paper publications and grants, teaching/mentoring students, and opportunities to
present my research at Caltech and national conferences. As a PhD student at Caltech, I will have access to
leaders well-versed in applying quantitative approaches to study developmental biology, state-of-the-art core
facilities, and cutting-edge coursework in both biology and statistics. By funding the rest of my PhD research,
this fellowship will enable me to uncover the fundamental principles that underlie retina de...

## Key facts

- **NIH application ID:** 10691337
- **Project number:** 5F31EY033220-03
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Martin Tran
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 5
- **Project period:** 2021-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10691337

## Citation

> US National Institutes of Health, RePORTER application 10691337, Determining the cell fate programs of mammalian retina development (5F31EY033220-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10691337. Licensed CC0.

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