# Understanding and rewiring cellular behavior with synthetic biology approaches

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $124,999

## Abstract

PROJECT SUMMARY
Human physiology depends on precise cellular responses to environmental signals. Specificity in responding
to environmental signals is achieved through specific proteomic, transcriptomic, epigenomic, and non-genetic
cell states. In physiological states, healthy cells function in harmony with their surrounding tissues, performing
specific functions in response to environmental stimuli. In disease, dysregulation of cell state can prevent
cells from producing necessary responses and lead to proliferation independent of physiological context.
Understanding how cell state drives cell function is essential for understanding tissue function in health and
disease, and is required for engineering cell therapies capable of specific behaviors encoded by their target
environments. Despite decades of research into single cell biology, we still don't understand the fundamental
principles that connect cell state with specificity in cellular responses to their environment
 In my proposed research, I will use synthetic biology tools to quantitatively probe the connection
between cell state and signaling specificity. My proposed work will provide insight into how cells of
different types achieve unique responses to their environments and will generate computational models that
can be used to engineer cellular behavior. To investigate how cells of different types uniquely respond to the
same signal, I will use optogenetics to perturb the model signal cAMP in candidate cell types of the early
mouse embryo and in an unbiased screen in developing zebrafish. My studies in mouse embryonic stem cells
will serve as a proof of principle for controlling cell type through intracellular signaling and for rewiring cellular
responses with genetic expression programs. My work in zebrafish will result in a predictive model that can
be used to infer a given cell's unique response to a stimulus using only transcriptional data from that cell.
Throughout this work, I will focus on generating interpretable computational models that can be used in the
future to engineer cellular behavior.
 I will achieve the above work through synthesizing my previous training in neuroscience, cell signaling,
and applied synthetic biology with proposed training in developmental biology, genomics, quantitative
modeling of cellular processes, and cellular engineering. I will also supplement my previous training and
experience in teaching and mentorship with new training in advocacy to best position myself to mentor my
future trainees and further justice, diversity, equity, and inclusion throughout the scientific enterprise. Through
my proposed research and training, I will be well positioned to transition to an independent position where I
can achieve my scientific and advocacy goals.

## Key facts

- **NIH application ID:** 10836543
- **Project number:** 5K99GM147825-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Zara Weinberg
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $124,999
- **Award type:** 5
- **Project period:** 2023-05-03 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836543

## Citation

> US National Institutes of Health, RePORTER application 10836543, Understanding and rewiring cellular behavior with synthetic biology approaches (5K99GM147825-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10836543. Licensed CC0.

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