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AWD12927 Admin Supplement to support undergraduate summer research experiences

AWD12927 支持本科生暑期研究经验的管理补充

基本信息

批准号：
10809114
负责人：
Whitney L Stoppel
金额：
$ 1万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10809114
关键词：
Address Agriculture Amino Acid Sequence Award Bacteria Binding Biochemical Biodiversity Biophysics Biopolymers Bombyx Bombyx mori Chemicals Clustered Regularly Interspaced Short Palindromic Repeats Collection Development Embryo Fiber Fibroins Florida Future Genetic Engineering Goals Growth Factor Healthcare Human Humidity Immune response In Vitro Injections Interruption Investigation Lepidoptera Life Cycle Stages Mammalian Cell Medical Device Medicine Modification Moths Muscle rehabilitation Natural regeneration Outcome Peptides Pharmacologic Substance Phase Phenotype Polymers Population Process Production Proteins Pupa Research Research Personnel Silk Site Solvents Stimulus Structure Students Tissue Engineering Transcriptional Regulation Translations United States Food and Drug Administration Universities Work aqueous bioink design doctoral student experience implantation improved in vivo manufacture mechanotransduction pathogen protein aminoacid sequence scale up success summer program summer research tool undergraduate student

项目摘要

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 consistently and reliably 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. 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 (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 through analysis of systemic and local immune responses in vivo, complete characterization of the new biopolymer structures, and investigation of mechanotransduction in these materials in vitro. Future work aims to leverage this new class of biopolymers for specific applications in pharmaceutical delivery, tissue engineering, and muscle rehabilitation.

用于医疗保健和医药的材料通常来自两大类(a)合成聚合物