![Biomedical Engineering ETDs](../../assets/md5images/cbe0f0c1d236b07a14265b4792e7f3af.jpg)
Biomedical Engineering ETDs
Publication Date
Summer 8-1-2024
Abstract
This dissertation explores the use of intrinsically disorder proteins (IDPs) in biomedical applications related to the detection and biosensing of nucleic-acid species. We engineer several low critical solution temperature (LCST) nucleic-acid binding elastin-like polypeptides (ELPs) as model IDPs and study their potential in biomedical application via interactions with short single-stranded (ss) DNA, tRNA and viral RNAs. First, we engineer a simple polycationic ELP capable of recruiting DNA on demand in a DNA-protein-rich condensate via LLPS. Moreover, we develop a modified Flory-Huggins theory to quantify the partitioning of DNA and protein upon coacervate formation with and without salts. We then design more robust NA-binding ELPs for use in the detection of NA pathogens such as NA extraction (NAE) or isolation to investigate the potential use of NA-binding ELPs as molecular chaperones of relevant DNA reactions. Our findings suggest that the genetically engineered IDPs we designed can concentrate complementary and structurally complex DNA strands in a biomolecular condensate to accelerate the kinetics of the reaction. Altogether, we show that IDPs can have a major impact on downstream processes involved in the process of NA testing.
Language
English
Keywords
Intrinsically disordered proteins, elastin-like polypeptides, membraneless organelles, nucleic acid extraction, nucleic acid binding, nucleic acid chaperones, strand annealing
Document Type
Dissertation
Degree Name
Biomedical Engineering
Level of Degree
Doctoral
Department Name
Biomedical Engineering
First Committee Member (Chair)
Dr. Nichlaus J. Carroll
Second Committee Member
Dr. Gabriel P. López
Third Committee Member
Dr. David S. Peabody
Fourth Committee Member
Dr. Andrew P. Shreve
Recommended Citation
Diez Perez, Telmo. "ENGINEERED NUCLEIC-ACID BINDING INTRINSICALLY DISORDERED PROTEINS FOR BIOMEDICAL APPLICATIONS." (2024). https://digitalrepository.unm.edu/bme_etds/41
Included in
Biological Engineering Commons, Biomaterials Commons, Molecular, Cellular, and Tissue Engineering Commons
Comments
This dissertation was submitted for an embargo.