# pH regulation of cell surface receptors

> **NIH NIH R35** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $74,999

## Abstract

ABSTRACT
Understanding proton-gating (H+-gating) of GPCR activity is a major new frontier in signaling biology.
GPCRs regularly encounter coincident H+ signals in a variety of contexts, such as endosomes, tumors,
synapses, inflamed tissue, and immune responses. However, the extent to which these signals regulate
GPCR function represents a significant gap in our understanding of cellular sensing, communication, and
drug discovery. The goal of our research program is to provide this insight for much of the GPCRome.
A major goal is the development of pH-intelligent nanobodies that enable the direct tracking and
regulation of GPCR function in normal and acidified conditions, with a longer-term plan is to develop the
most promising of these precision tools into therapeutics. We have had much success in these efforts.
We have successfully engineered the necessary nanobody discovery platform and validated it using
known GPCR-nanobody pairs. We have also computationally designed and manufactured new synthetic
nanobody libraries which we have begun to screen against pools of diverse GPCRs. Because of our
large library sizes and high hit rates, we have discovered a bottleneck in the plating, cataloging, picking,
and characterization of yeast colonies carrying putative nanobody hits. The instrument we are requesting,
a Mini Qpix small footprint microbial colony picker, will overcome this bottleneck and enable us to expand
our processing from hundreds to thousands of nanobody hits. Such capabilities would greatly accelerate
the discovery of nanobody regulators of GPCRs and have the potential to illuminate nanobody diversity
at a depth and scale necessary for training artificial intelligence algorithms for de novo nanobody design.
As such, NIGMS support for our instrument request would catalyze a substantial leap forward in the field.

## Key facts

- **NIH application ID:** 10798554
- **Project number:** 3R35GM119518-07S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Daniel Isom
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $74,999
- **Award type:** 3
- **Project period:** 2016-08-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798554

## Citation

> US National Institutes of Health, RePORTER application 10798554, pH regulation of cell surface receptors (3R35GM119518-07S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10798554. Licensed CC0.

---

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