# Leveraging biodiversity and utilizing genetic engineering to expand the structure and function of silk fibroin biopolymers for biomedical applications

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2022 · $353,751

## Abstract

Project Summary
Materials for applications in healthcare and medicine usually come from two main groups (a) synthetic polymers
specifically designed to achieve a certain goal or (b) naturally derived biopolymers that are leveraged in their
native or slightly modified state for a specific goal. The advantage of being a synthetic chemist is that technically,
if you can synthesize it, the possibilities are infinite, but the downfall is that often solvents or portions of the
polymer cause cytocompability issues or concerns when it comes to translation and implantation in a human.
Alternatively, unmodified natural biopolymers, or proteins, have an easier path toward Food and Drug
Administration's approval, but lack the customizability afforded in synthesis or chemical modification. Genetic
engineering via production of small peptides in bacteria has improved the availability of customizable short
peptides, but proteins on the order of hundreds of kilodaltons cannot be produced this way. This is the case for
the silk fibroin biopolymers isolated from caterpillars in the Lepidoptera order, where the heavy chain of silk
fibroin is known to be over 300 kilodaltons in length. Genetic engineering, using tools such as CRISPR or
PiggyBac, provides an avenue for theoretically modifying the sequence of silk proteins, which has been
attempted with limited success in the domesticated silkworm, Bombyx mori. However, silk is collected from the
cocoon of the B. mori pupae, meaning that the life cycle of this silkworm is interrupted, making it difficult to
maintain these modified populations or assess phenotypes in a high-throughput manner. To address this, silk
fibroin will be isolated from an entirely different silk-producing species: Plodia interpunctella, or the Indianmeal
moth. Under specific conditions, this agricultural pest produces sheets of silk prior to entering the cocooning
phase. These easily collectable sheets of silk fibers can then be cleaned, degummed, and regenerated to an
aqueous biopolymer solution. Moreover, unlike B. mori, P. interpunctella silk collection does not interrupt the life
cycle of the silkworm/moth and these silkworms are easier to stably genetically modify though embryo injections
compared to B. mori. In this Maximizing Investigators' Research Award, genetic engineering will be leveraged to
modify the silk fibroin protein sequence at the organismal level, adding in new peptide sequences such as
mammalian cell binding motifs or sites for human growth factor sequestration. Scale-up of the process will be
achieved via transcriptional regulation of silk fibroin as a function of external stimuli such as humidity or
pathogens. Together, these two strategies for enhancing the bio-functionality of the silk fibroin protein and the
scale-up required for advanced manufacturing of medical devices or materials will be explored. The outcomes
of this work include full biophysical, biochemical, and in vivo characterization of these materials throu...

## Key facts

- **NIH application ID:** 10499174
- **Project number:** 1R35GM147041-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Whitney L Stoppel
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $353,751
- **Award type:** 1
- **Project period:** 2022-08-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499174

## Citation

> US National Institutes of Health, RePORTER application 10499174, Leveraging biodiversity and utilizing genetic engineering to expand the structure and function of silk fibroin biopolymers for biomedical applications (1R35GM147041-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499174. Licensed CC0.

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