# Molecular Mechanisms of Signal Transduction Involving Light, Redox and Transmembrane Complexes

> **NIH NIH R35** · CORNELL UNIVERSITY · 2020 · $745,405

## Abstract

The Crane group studies mechanisms of signal transduction with the overall goal of understanding behavior at
the molecular level. This understanding will be achieved by defining the structure and dynamics of key
macromolecular complexes that coordinate gene expression and transmembrane signaling in two systems that
rely on highly cooperative interactions to respond to light, redox and chemical environment. The first, bacterial
chemotaxis, concerns the motion of prokaryotic cells toward external stimulants. Chemotaxis is a paradigm for
understanding transmembrane communication, intracellular information transfer, and motility. Importantly,
many human pathogens that cause diseases such as cholera, gastric cancer and lyme rely on chemotaxis to
establish infection. The sensory apparatus underlying chemotaxis, hereafter called “the chemosome”, displays
amazing sensitivity, dynamic range and a rudimentary molecular memory. In the chemosome, receptors,
histidine kinases (CheA) and coupling proteins assemble into a specific architecture, whose details are just
emerging. This proposal continues efforts to understand chemosome assembly, chemoreceptor conformational
signaling, and ultimately, CheA regulation through restructuring of the receptor arrays. Chemosome output
modulates Nature's consummate nanomachine – the flagella motor. The ultrastructure of the switch complex
within the motor will be defined to understand torque generation, direction switching and response to
chemosome signals. The second system, eukaryotic circadian clocks, comprises cell-autonomous timing
devices that pace metabolism to the diurnal cycle. Clocks are composed of transcriptional-translational
feedback loops (TTFLs) within which repressor proteins inhibit the transcriptional activators of their own genes.
Light entrains the clock phase by stimulating photosensors that impinge directly on the TTFLs. In humans,
aberrant clock function causes mental illness (sleep disorders, depression, mania), cell growth deregulation
(cancer) and metabolic defects (diabetes and obesity). This project proposes structural and mechanistic
investigations of the key repressor and light-setting activities common to clocks in higher organisms.
Biophysical studies will be conducted on the circadian proteins of fungi (Neurospora crassa) and flies
(Drosophila melanogaster). Both model organisms provide genetic systems and behavioral assays to probe
the biological relevance of mechanistic insights. A complimentary set of techniques including X-ray
crystallography, small-angle X-ray scattering, optical spectroscopy, cryo-electron microscopy and pulse-dipolar
ESR spectroscopy (PDS) will be applied to accomplish these goals. For PDS, new strategies for incorporating
spin probes based on nitroxides, flavins, nucleotides, and metal ions will be developed and deployed. Overall,
this program aims to provide a molecular understanding for sensing and response in bacterial chemotaxis and
eukaryotic circadian rhythms...

## Key facts

- **NIH application ID:** 9938581
- **Project number:** 5R35GM122535-04
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** BRIAN R CRANE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $745,405
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938581

## Citation

> US National Institutes of Health, RePORTER application 9938581, Molecular Mechanisms of Signal Transduction Involving Light, Redox and Transmembrane Complexes (5R35GM122535-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9938581. Licensed CC0.

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