# ILLUMINATING CELLULAR INDIVIDUALITY THROUGH BACTERIOPHAGE INFECTION

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2023 · $347,321

## Abstract

PROJECT SUMMARY / ABSTRACT
A key goal of biophysics is to predict the behavior of living systems. This goal is hampered by the fact that, when
examined at the single-cell level, this behavior appears largely unpredictable: Genetically identical cells, within
a uniform environment, exhibit heterogeneous phenotypes in terms of gene expression, signaling, and
consequent fate choice. This cellular individuality is observed throughout biology, from the emergence of
antibiotic resistance among bacteria, to cell differentiation in the early mammalian embryo, and numerous other
examples.
Studies over the last two decades have pinpointed the stochastic origins of cellular individuality, by
demonstrating that the inherent randomness (“noise”) of single-molecule events can be amplified into protein
number fluctuations at the cellular level. The picture that emerged from those studies is of living cells as “noisy
machines”, incapable of high precision, whose fate choices are subject to significant randomness. But the
widespread success of the “noise” concept in describing cellular heterogeneity also points to its weakness: It is
easy to describe single-cell properties as “stochastic” and map them into statistical distributions, but doing so
does not mean that we understand the underlying cellular process. On the contrary, by creating a façade of
understanding, a stochastic description may impede our efforts to uncover the deterministic factors that drive
single-cell behavior. Recent years have seen a growing awareness of this caveat and an increase in efforts to
identify the deterministic drivers (so-called “hidden variables”) of cellular individuality, but it is fair to say that we
still lack a satisfactory picture for what drives single-cell behavior even in the simplest systems, to say nothing
of more complex ones.
Research goal. The choice between rapid cell death (lysis) and viral dormancy (lysogeny), following infection of
E. coli by bacteriophage lambda, serves as a paradigm for the way genetic networks drive cell fate decisions,
and for the purported role of molecular randomness in this process. Building on our work over the last decade,
we will use lambda infection to identify hidden drivers of cellular individuality in gene regulation and fate choice.
By revealing how deterministic the decision process is, we aim to establish lambda as a paradigm for precise—
rather than “noisy”—cell fate choice. In parallel to the work on lambda, we will continue to develop tools for the
manipulation, imaging, analysis, and modeling of individual cells, and apply them in collaborative projects
addressing cellular individuality across diverse biological contexts.

## Key facts

- **NIH application ID:** 10656197
- **Project number:** 5R35GM140709-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Ido Golding
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $347,321
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656197

## Citation

> US National Institutes of Health, RePORTER application 10656197, ILLUMINATING CELLULAR INDIVIDUALITY THROUGH BACTERIOPHAGE INFECTION (5R35GM140709-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10656197. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*