# Bioorthogonal temporospatial tools - Admin Supple Equipment

> **NIH NIH R35** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $248,743

## Abstract

Living systems choreograph molecular events with precise control—place, time, kinetics, and intensity
—and record memories of those occurrences in synaptic networks, gene expression, epigenetic
marks, and myriad other circuits that govern the where&when of biologic responses. Visualizing this
choreography and tracing these histories are tasks that chemists and biologists can accomplish with
only partial accuracy, considerable effort, and limited temporal range. Our research agendas are thus
focused on constructing new chemical tools for temporospatial analysis of living systems, and
organized around the emergent properties that result from deploying next-level bioorthogonal
chemistries within multi-layered (bio)molecular architectures. The resulting hybrid systems circumvent
perennial challenges, achieving: i) simultaneous speed/stability, for efficient real-time molecular
machinery and longitudinal performance in vivo; ii) sensitivity for detection of rare/unique events; and
iii) specificity/multiplicity, for accurate detection and fine-grained molecular encoding of (sub)cellular
histories across time.
Building on the momentum of ongoing mechanistic investigations and the success of our recent effort
to achieve multiplexed imaging of living cells and tissues, our goals for the next five years extend
bioorthogonal chemistry in applications that exploit two/three dimensional topologies, rather than
singular ligation/cleavage events, and in architectures that leverage nucleic acid hybridization to
encode sequence recognition, accelerate reaction kinetics, and enable signal amplification. In one set
of projects, we aim to create self-amplifying programmable bioorthogonal reactions, elaborate the
capabilities of this new toolkit, and apply them to transform our methods for visualizing living cells and
tissues. In another, we have envisioned sequence-generating architectures that convert biocompatible
chemical reactivity into amplifiable biological information, establishing the concepts of bioorthogonal
translation and sequegenicity. With scaffolds that readily integrate into the workflows of existing high-
performance nucleic acid biotechnologies, we anticipate broad applicability and rapid downstream
development of a new generation of tools for tracking (bio)molecules, individual cells, and populations.

## Key facts

- **NIH application ID:** 11034421
- **Project number:** 3R35GM150508-02S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jonathan Carlson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $248,743
- **Award type:** 3
- **Project period:** 2023-07-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11034421

## Citation

> US National Institutes of Health, RePORTER application 11034421, Bioorthogonal temporospatial tools - Admin Supple Equipment (3R35GM150508-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11034421. Licensed CC0.

---

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