# Genetically Encoded Smart Biohybrid Materials

> **NIH NIH R35** · DUKE UNIVERSITY · 2020 · $385,285

## Abstract

Abstract
The proposed work in this MIRA application leverages my long-standing interest and expertise in the design of genetically
encoded stimulus-responsive peptide polymers. My group pioneered the development of recombinant elastin-like polypeptides
(ELPs) that exhibit lower critical solution temperature (LCST) phase behavior. We have also, in parallel, pioneered the
development of high-throughput methods for the assembly of highly repetitive genes that we used to create the largest extant
library of recombinant peptide polymers. Characterization of their aqueous phase behavior led to the discovery of sequence
heuristics that can be used for the de novo used design of peptide polymers that exhibit LCST phase behavior and a class of
resilin-like polypeptides (RLPs) that exhibit the converse — upper critical solution phase transition (UCST) phase behavior.
Building upon this work, we will explore two new areas in this proposal. First, we will investigate how we can recapitulate the
hierarchical structure and properties exhibited by biological materials by the design of partially ordered polymers (POPs) —that
consist of disordered polypeptides embedded with a periodically recurring secondary structure motif— that exhibit temperature
triggered hierarchical self-assembly into macroscopic materials that mimic the in vivo organization of structural proteins like
elastin networks. We will carry out a systematic exploration of the design of new POPs, to verify that the combination of order
and disorder at the chain segment level is a new and robust design principle that will yield materials with hierarchical self-
assembly across many length scales. Second, we will develop a new line of investigation on genetically encoded biohybrid
polymers via post-translational modifications (PTMs) that precisely combine peptide and non-peptide components to create
biomaterials that exhibit triggered, hierarchical self-assembly into macroscopic materials. In this aim, we will expand upon our
initial work on in vivo myristoylation of ELPs and UCST exhibiting RLPs to investigate if we can convert structure-directing
peptides into myristoylation substrates, to create myristoylated polypeptides where the myristoylated segment can direct
hierarchical self-assembly of the entire construct. We will also investigate modification of ELPs and RLPs with cholesterol that
has the potential to direct self-assembly, and phosphorylation, which will provide a unique trigger of self-assembly. Much remains
to be done in both areas, as our preliminary foray into these new areas only hint at the enormous possibilities in the molecular
design of new biomaterials enabled by these approaches. The work we propose herein promises to yield new biomaterials with
interesting structures and properties with a host of applications in biotechnology and medicine.

## Key facts

- **NIH application ID:** 10013243
- **Project number:** 5R35GM127042-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Ashutosh Chilkoti
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,285
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013243

## Citation

> US National Institutes of Health, RePORTER application 10013243, Genetically Encoded Smart Biohybrid Materials (5R35GM127042-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10013243. Licensed CC0.

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