# Molecular Mechanisms and Biochemical Circuits for Adaptation in Biological Systems

> **NIH NIH R35** · IBM THOMAS J. WATSON RESEARCH CENTER · 2021 · $279,867

## Abstract

Project Summary
Adaptation is one of the most important and defining properties of all biological systems ranging from a single
cell to multi-cellular organisms to populations of interacting species. Adaptation allows living systems to adjust
themselves in response to environmental changes and stresses to maintain their normal functions. Therefore,
the ability to adapt is crucial for the health and fitness of living systems from human to a single cell. For
adaptation at the cellular level, much progresses have been made in identifying key molecular components
relevant for adaptation and in measuring the adaptive input-output responses in individual systems. However,
despite these advances, many fundamental questions on cellular level adaptation remain unresolved. What are
the general system-level molecular mechanisms for adaptation to different types of (chemical and mechanical)
stimuli in living cells? Are there any universal design principles governing the underlying biochemical pathways
(circuits) that are responsible for the vast variety of adaptive behaviors in cells?
In this proposed program, we aim to address these questions broadly to bridge the gap between molecular
interactions and system-level adaptation behaviors by using an integrated approach that combines theoretical
analysis and computational modeling with quantitative experiments from our experimental collaborators' labs.
We plan to study three representative cellular systems: 1) adaptation to chemical signals in bacterium cells
(Escherichia coli); 2) adaptation to mechanical signals in bacterial flagellar motor (BFM); 3) adaptation to odor
stimuli in olfactory sensory neurons (OSN). In each of these systems, we will develop a system-level model
based on known molecular components and their interactions. These system-level models will allow us to
verify/falsify different possible molecular mechanisms (hypotheses) against the system level input-output
measurements. By comparing the molecular mechanisms for adaptation in these diverse systems, we aim to
uncover general features (design principles) in the underlying biochemical pathways (circuits), which should
provide a general framework for understanding other cellular adaptation systems such as metal homeostasis,
response to osmotic pressure, chemotaxis in Eukaryotic cells, and adaptations of sensory neurons in different
sensory modalities.

## Key facts

- **NIH application ID:** 10248476
- **Project number:** 5R35GM131734-03
- **Recipient organization:** IBM THOMAS J. WATSON RESEARCH CENTER
- **Principal Investigator:** Yuhai Tu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $279,867
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248476

## Citation

> US National Institutes of Health, RePORTER application 10248476, Molecular Mechanisms and Biochemical Circuits for Adaptation in Biological Systems (5R35GM131734-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10248476. Licensed CC0.

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