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Articles 1 - 30 of 80
Full-Text Articles in Life Sciences
Multi-Scale Simulations Of Dynamic Protein Structures And Interactions, Yumeng Zhang
Multi-Scale Simulations Of Dynamic Protein Structures And Interactions, Yumeng Zhang
Doctoral Dissertations
Intrinsically disordered proteins (IDPs) are functional proteins that lack stable tertiary structures in the unbound state. They frequently remain dynamic even within specific complexes and assemblies. IDPs are major components of cellular regulatory networks and have been associated with cancers, diabetes, neurodegenerative diseases, and other human diseases. Computer simulations are essential for deriving a molecular description of the disordered protein ensembles and dynamic interactions for mechanistic understanding of IDPs in biology, diseases, and therapeutics. However, accurate simulation of the heterogeneous ensembles and dynamic interactions of IDPs is extremely challenging because of both the prohibitive computational cost and demanding force field …
High Resolution Mass Spectrometry As A Platform For The Analysis Of Polyoxometalates, Their Solution Phase Dynamics, And Their Biological Interactions., Daniel T. Favre
High Resolution Mass Spectrometry As A Platform For The Analysis Of Polyoxometalates, Their Solution Phase Dynamics, And Their Biological Interactions., Daniel T. Favre
Doctoral Dissertations
Polyoxometalates (POMs) are a class of inorganic molecule of increasing interest to the inorganic, bioinorganic and catalytic communities among many others. While their prevalence in research has increased, tools and methodologies for the analysis of their fundamental characteristics still need further development. Decavanadate (V10) specifically has been postulated to have several unique properties that have not been confirmed independently. Mass spectrometry (MS) and its ability to determine the composition of solution phase species by both mass and charge is uniquely well suited to the analysis of POMs. In this work we utilized high-resolution mass spectrometry to characterize V10 in aqueous …
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Doctoral Dissertations
Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …
Atomistic Simulations Of Intrinsically Disordered Protein Folding And Dynamics, Xiping Gong
Atomistic Simulations Of Intrinsically Disordered Protein Folding And Dynamics, Xiping Gong
Doctoral Dissertations
Intrinsically disordered proteins (IDPs) are crucial in biology and human diseases, necessitating a comprehensive understanding of their structure, dynamics, and interactions. Atomistic simulations have emerged as a key tool for unraveling the molecular intricacies and establishing mechanistic insights into how these proteins facilitate diverse biological functions. However, achieving accurate simulations requires both an appropriate protein force field capable of describing the energy landscape of functionally relevant IDP conformations and sufficient conformational sampling to capture the free energy landscape of IDP dynamics. These factors are fundamental in comprehending potential IDP structures, dynamics, and interactions. I first conducted explicit solvent simulations to …
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian
Doctoral Dissertations
The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …
Intracellular Delivery Of Therapeutic Biomolecules Through Versatile Polymer Nanotechnology, David C. Luther
Intracellular Delivery Of Therapeutic Biomolecules Through Versatile Polymer Nanotechnology, David C. Luther
Doctoral Dissertations
Advancing pharmaceutical technology has made it possible to treat diseases once considered ‘undruggable.’ Access to these new pharmaceutical targets is possible thanks to the advent of protein and nucleic acid therapeutics. Responses to the COVID-19 pandemic, as well as cutting-edge treatments for cancer and multiple sclerosis have centered on these biologic therapies, promising even greater value in the future. However, their utility is limited at a cellular level by inability to cross the plasma membrane. Nanocarrier technologies encapsulate therapeutics and facilitate uptake into the cell but are often trapped and degraded in endosomes. Arginine-functionalized gold nanoparticles (Arg-NPs) provide efficient, direct …
Deciphering Protein Higher-Order Structure And Interactions Via Diethylpyrocarbonate Labeling-Mass Spectrometry, Xiao Pan
Doctoral Dissertations
The study of protein higher-order structures is vital because it is closely related to the investigation of protein folding, aggregation, interaction and protein therapeutics. Consequently, numerous biochemical and biophysical tools have been developed to study protein higher-order structures in many different situations. The combination of covalent labeling (CL) and mass spectrometry (MS) has emerged as a powerful tool for studying protein structures and offers many advantages over other traditional techniques, such as better structural coverage, high throughput, high sensitivity, and the ability to study proteins in mixtures. This dissertation focuses on diethylpyrocarbonate (DEPC) as an effective CL reagent that can …
Quantitative Imaging Of Tensile Forces At Cell-Cell Junction With Dna-Based Probes, Puspam Keshri
Quantitative Imaging Of Tensile Forces At Cell-Cell Junction With Dna-Based Probes, Puspam Keshri
Doctoral Dissertations
Mechanical forces are an integral part in biology, they regulate several cellular properties, such as morphology, proliferation, migration. These forces are also involved in receptor signaling and the differentiation of different cell types. Different proteins and biomolecules such as cadherin, integrin, notch proteins are essential elements of these processes. Measuring these intercellular forces are challenging considering the minimal intensity (piconewton-level) of these molecular forces. In our lab, we have developed a membrane DNA tension probe (MDTP) that uses a DNA hairpin module to sense tensile forces and has a lipid anchor to modify onto live-cell membranes. The programmability of DNA …
Antibiotic Sensitivity Testing Of Foodborne Bacteria Using Surface-Enhanced Raman Spectroscopy, Joshua Gukowsky
Antibiotic Sensitivity Testing Of Foodborne Bacteria Using Surface-Enhanced Raman Spectroscopy, Joshua Gukowsky
Doctoral Dissertations
The spread of antibiotic resistant bacteria around the world has become a major public health issue, and it is essential that effective detection methods exist for identifying these organisms and preventing them from spreading throughout our food systems and into the environment. The goal of this research is to develop a novel analytical procedure that is capable of easily identifying antibiotic resistance in bacterial samples, and also provides more information about the biochemical characteristics of the bacteria and their responses to antibiotic exposure. Surface-enhanced Raman Spectroscopy (SERS), an analytical technique that uses light scattering to produce a spectrum based on …
Amyloidogenesis Of Β-2-Microglobulin Studied By Mass Spectrometry And Covalent Labeling, Blaise G. Arden
Amyloidogenesis Of Β-2-Microglobulin Studied By Mass Spectrometry And Covalent Labeling, Blaise G. Arden
Doctoral Dissertations
Amyloid-forming proteins are implicated in a number of debilitating diseases. While many amyloid-forming proteins are well studied, the early stages of amyloidosis are still not well understood on a molecular level. Covalent labeling, combined with mass spectrometry (CL-MS), is uniquely well suited to provide molecular-level insight into the factors governing the early stages of amyloidosis. This dissertation leverages CL-MS techniques to examine the early stages of β-2-microglobulin (β2m) amyloidosis. β2m is the protein that forms amyloids in the condition known as dialysis-related amyloidosis. An automated CL-MS technique that uses dimethyl(2-hydroxy-5-nitrobenzyl) sulfonium bromide as a labeling reagent was developed and used …
Investigative Mechanisms To Exploit Caspase-Induced Apoptosis Using Polymeric Nanogels, Francesca Edith Anson
Investigative Mechanisms To Exploit Caspase-Induced Apoptosis Using Polymeric Nanogels, Francesca Edith Anson
Doctoral Dissertations
Cysteine aspartate proteases (caspases) act as the molecular scissors of cell death, disintegrating diverse cellular components necessary for survival and growth via proteolysis. Caspases are tightly regulated through a myriad of mechanisms including proteolytic processing, structural changes, post-translational modifications and metal binding. Correspondingly, cancers have evolved numerous resistance and desensitization mechanisms upstream or within the caspase pathway to avoid death signals. These mechanisms are extremely diverse and are not fully understood however, the field overwhelming suggests caspase activity and caspase inhibition antagonism to be critical for efficacious cancer therapies. Accordingly, exploiting the role of caspases in apoptosis has become an …
Evidence For The Role Of Cyp51a And Xenobiotic Detoxification In Differential Sensitivity To Azole Fungicides In Boxwood Blight Pathogens, Stefanos Stravoravdis, Robert E. Marra, Nicholas R. Leblanc, Joanne Crouch, Jonathan P. Hulvey
Evidence For The Role Of Cyp51a And Xenobiotic Detoxification In Differential Sensitivity To Azole Fungicides In Boxwood Blight Pathogens, Stefanos Stravoravdis, Robert E. Marra, Nicholas R. Leblanc, Joanne Crouch, Jonathan P. Hulvey
Microbiology Department Faculty Publication Series
Boxwood blight, a fungal disease of ornamental plants (Buxus spp.), is caused by two sister species, Calonectria pseudonaviculata (Cps) and C. henricotiae (Che). Compared to Cps, Che is documented to display reduced sensitivity to fungicides, including the azole class of antifungals, which block synthesis of a key fungal membrane component, ergosterol. A previous study reported an ergosterol biosynthesis gene in Cps, CYP51A, to be a pseudogene, and RNA-Seq data confirm that a functional CYP51A is expressed only in Che. The lack of additional ergosterol biosynthesis genes showing significant differential expression suggests that the functional CYP51A in Che could contribute to …
Polymeric Nanoparticles Active Against Dual-Species Bacterial Biofilms, Jessa Marie V. Makabenta, Jungmi Park, Cheng-Hsuan Li, Aritra Nath Chattopadhyay, Ahmed Nabawy, Ryan F. Landis, Akash Gupta, Suzannah Schmidt-Malan, Robin Patel, Vincent M. Rotello
Polymeric Nanoparticles Active Against Dual-Species Bacterial Biofilms, Jessa Marie V. Makabenta, Jungmi Park, Cheng-Hsuan Li, Aritra Nath Chattopadhyay, Ahmed Nabawy, Ryan F. Landis, Akash Gupta, Suzannah Schmidt-Malan, Robin Patel, Vincent M. Rotello
Chemistry Department Faculty Publication Series
Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species. The co-existence of multiple species of bacteria in biofilms exacerbates therapeutic challenges and can render traditional antibiotics ineffective. Polymeric nanoparticles offer alternative antimicrobial approaches to antibiotics, owing to their tunable physico-chemical properties. Here, we report the efficacy of poly(oxanorborneneimide) (PONI)-based antimicrobial polymeric nanoparticles (PNPs) against multi-species bacterial biofilms. PNPs showed good dual-species biofilm penetration profiles as confirmed by confocal laser scanning microscopy. …
Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta
Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta
Doctoral Dissertations
Biologic drugs have gained enormous research attention in recent years as reflected by the development of multiple candidates to the clinical pipelines and an increased percentage of FDA approval. This is reasoned by the fact that biologics have been proven to deliver more predictive and promising benefits for many hard-to-cure diseases by ‘drugging the undruggable’ targets. However, the challenges associated with biologic drug development are multi-fold, viz, poor encapsulation efficacy, systemic instability, low cellular internalization and endosomal escape capability. Thus, it is essential to develop new molecular strategies that can not only address the associated drug delivery challenges, but also …
Engineered Proteins As Tools To Understand Ubiquitin Signaling, Lin Hui Chang
Engineered Proteins As Tools To Understand Ubiquitin Signaling, Lin Hui Chang
Doctoral Dissertations
Ubiquitin is a 76 amino acids protein that is evolutionary conserved in eukaryotes. It is an important signaling molecule in a plethora biological events, such as protein degradation, DNA damage response, and transcription. This thesis aims to develop engineered protein as a tool to study ubiquitin signaling. Through targeted mutagenesis and directed evolution, a deubiquitinase is reprogrammed into a transamidase, which lead to the generation of ubiquitinprotein conjugates with discrete ubiquitin linkages through auto-ubiquitination. These ubiquitin-protein conjugates could be used as a model substrate to profile their interaction of different ubiquitin interacting proteins. In addition, using directed evolution and deep …
Analysis Of Titanium Dioxide Nanoparticles In Foods Using Raman Spectroscopic Techniques, Janamkumar Pandya
Analysis Of Titanium Dioxide Nanoparticles In Foods Using Raman Spectroscopic Techniques, Janamkumar Pandya
Doctoral Dissertations
Titanium dioxide (TiO2) and its nanoparticles (NPs) are widely used in various applications. Recently, the presence of TiO2 NPs in food and consumer products raised safety concerns to human health and the environment. The goal of this project is to explore the capability of Raman Spectroscopy in the analysis of TiO2-NPs and apply this technique for the analysis of TiO2-NPs in food and environmental samples. Two approaches, i.e. the ligand-based and the mapping-based, were evaluated. The ligand-based approach utilized the surface enhanced Raman scattering (SERS) property of the TiO2 NPs as a substrate to enhance the signal of a surface …
Investigating The Accumulation, Sub-Organ Distribution, And Biochemical Effects Of Nanomaterials Using Mass Spectrometry, Kristen Nicole Sikora
Investigating The Accumulation, Sub-Organ Distribution, And Biochemical Effects Of Nanomaterials Using Mass Spectrometry, Kristen Nicole Sikora
Doctoral Dissertations
Gold nanoparticles (AuNPs) are attractive materials for use in various biomedical applications, such as therapeutic delivery, due to their unique chemical properties and modular tunability. Mass spectrometry methods, including laser desorption/ionization mass spectrometry (LDI-MS) and inductively coupled plasma mass spectrometry (ICP-MS) have been successfully used to evaluate the distribution of AuNPs in complex biological systems. As new AuNP-based materials are developed for applications in therapeutic delivery, it is essential to simultaneously develop analytical techniques that can comprehensively assess their behavior in vivo. In this dissertation, novel mass spectrometric methods have been developed and utilized to evaluate the uptake, distribution, …
Study Of The Role Of Biologically-Relevant, Labile Nickel Pools In The Maturation Of Nickel-Dependent Enzymes, Priyanka Basak
Study Of The Role Of Biologically-Relevant, Labile Nickel Pools In The Maturation Of Nickel-Dependent Enzymes, Priyanka Basak
Doctoral Dissertations
Cellular nickel pools, comprised of static and labile pools of nickel complexes, play important roles in maintaining nickel homeostasis in various organisms (microbes, fungi, and plants), which utilize it as a cofactor of one or more nickel enzymes that catalyze specific reactions and are essential for their proper growth and survival in various ecological niches. Like other metals, tight regulation of cellular nickel levels is critical to prevent toxic effects of nickel deprivation, nickel overload, and ‘free’ nickel. While more static nickel pools include nickel tightly bound to nickel-dependent enzymes, nickel in the labile pool is exchangeable and weakly bound …
Structural Analysis Of Protein Therapeutics Using Covalent Labeling – Mass Spectrometry, Patanachai Limpikirati
Structural Analysis Of Protein Therapeutics Using Covalent Labeling – Mass Spectrometry, Patanachai Limpikirati
Doctoral Dissertations
Using mass spectrometry (MS) to obtain information about a higher order structure of protein requires that a protein’s structural properties are encoded into the mass of that protein. Covalent labeling (CL) with reagents that can irreversibly modify solvent accessible amino acid side chains is an effective way to encode structural information into the mass of a protein, as this information can be read-out in a straightforward manner using standard MS-based proteomics techniques. The differential reactivity of proteins under two or more conditions can be used to distinguish protein topologies, conformations, and/or binding sites. CL-MS methods have been effectively used for …
Characterization Of Biodistribution Of Transferrin And Receptor Binding Mechanism By Mass Spectrometry, Hanwei Zhao
Characterization Of Biodistribution Of Transferrin And Receptor Binding Mechanism By Mass Spectrometry, Hanwei Zhao
Doctoral Dissertations
Protein-based therapeutics have emerged as a key driver of rapid growth in drug development pipelines. However, developing such protein drugs is not straightforward in most cases, the existence of physiological barriers greatly restricts the efficient delivery of many therapeutic molecules, and therefore limits their clinical applications. A promising way to address this challenge takes advantage of certain transport protein which can effectively across and enhance the permeability of these barriers, such as transferrin (Tf) which can be internalized by malignant cells and cross physiological barriers via transferrin receptor (TfR)-mediated endocytosis and transcytosis. However, developing such products is impossible without successfully …
Covalent Labeling-Mass Spectrometry For Characterizing Protein-Ligand Complexes, Tianying Liu
Covalent Labeling-Mass Spectrometry For Characterizing Protein-Ligand Complexes, Tianying Liu
Doctoral Dissertations
This dissertation focuses on applying covalent labeling (CL) and mass spectrometry (MS) for characterizing protein-ligand complexes. Understanding protein-ligand interactions has both fundamental and applied significance. Covalent labeling is a protein surface modification technique that selectively modifies solvent-exposed amino acid side chains of proteins. A covalent bond is formed between the functional groups of labeling reagent and protein’s side chain. One of the key factors that affects CL reactivity is a side chain’s solvent accessibility. Ligand binding protects residues on the protein surface from being labeled, and residues involved in ligand binding can be indicated via decreases in labeling extents. The …
Characterization Of Β-2-Microglobulin Pre-Amyloid Oligomers And Their Role In Amyloid Inhibition, Tyler M. Marcinko
Characterization Of Β-2-Microglobulin Pre-Amyloid Oligomers And Their Role In Amyloid Inhibition, Tyler M. Marcinko
Doctoral Dissertations
In dialysis patients, β-2 microglobulin (β2m) can aggregate and eventually form amyloid fibrils in a condition known as dialysis-related amyloidosis, which deleteriously affects joint, bone, and organ function, and eventually causes organ failure. To understand the early stages of the amyloid assembly process, we have employed a series of biophysical tools including chromatography, spectroscopy, and most especially, native electrospray ionization (ESI) together with ion mobility mass spectrometry (IM-MS) to study soluble pre-amyloid oligomeric species. We have also collaborated and integrated computational modeling to help better understand and rationalize the structural basis behind oligomerization. Recently, several small molecules have been identified …
Protein Detection And Structural Characterization By Mass Spectrometry Using Supramolecular Assemblies And Small Molecules, Bo Zhao
Doctoral Dissertations
Mass spectrometry (MS) has played an increasingly prominent role in proteomics and structure biology because it shows superior capabilities in identification, quantification and structural characterization of proteins. To realize its full potential in protein analysis, significant progress has been made in developing innovative techniques and reagents that can couple to MS detection. This dissertation demonstrates the use of polymeric supramolecular assemblies for enhanced protein detection in complex biological mixtures by MS. An amphiphilic random co-polymer scaffold is developed to form functional supramolecular assemblies for protein/ peptide enrichment. The influences of charge density and functional group pKa on host-guest interactions …
Multiscale Simulations Of Intrinsically Disordered Proteins, Xiaorong Liu
Multiscale Simulations Of Intrinsically Disordered Proteins, Xiaorong Liu
Doctoral Dissertations
Intrinsically disordered proteins (IDPs) lack stable secondary and/or tertiary structures under physiological conditions. The have now been recognized to play important roles in numerous biological processes, particularly cellular signaling and regulation. Mutation of IDPs are frequently associated with human diseases, such as cancers and neuron degenerative diseases. Therefore, it is important to understand the structure, dynamics, and interactions of IDPs, so as to establish the mechanistic basis of how intrinsic disorder mediates versatile functions and how such mechanisms may fail in human diseases. However, the heterogeneous structural ensembles of IDPs are not amenable to high resolution characterization solely through experimental …
Bio-Inspired Polymers That Bind And Deliver Protein Cargo, Nicholas D. Posey
Bio-Inspired Polymers That Bind And Deliver Protein Cargo, Nicholas D. Posey
Doctoral Dissertations
Delivering functional proteins and antibodies into cells can allow researchers to probe the intracellular environment, discover new cellular pathways, and pioneer new therapeutics. However, the entry of exogenous, charged molecules, like proteins, into the cell is usually restricted by the membrane, thereby hindering intracellular delivery. Membrane permeable molecules such as cell penetrating peptides (CPPs) and protein transduction domains (PTDs) can be used to bypass the cell membrane and deliver protein into the cell, but these peptides involve iterative and laborious syntheses and are limited in terms of their chemical diversity. This dissertation work overall focuses on the design and synthesis …
Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund
Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund
Doctoral Dissertations
The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular applications. Consequently, proteins with intracellular targets represent an enormous, yet under studied avenue for therapeutics. Extended research has aimed at facilitating intracellular delivery of exogenous proteins using protein transduction domains (PTDs), which allow transport of bioactive molecules into cells. Synthetic polymers, inspired by PTDs, provide a well-controlled platform to vary molecular architecture for structure activity relationship studies. Specifically, this thesis focuses on the use of ring-opening metathesis, a facile and efficient polymerization technique, through which we can vary structural parameters to optimize delivery of …
Effects Of Floral Phytochemicals On Growth And Evolution Of A Parasite Of Bumble Bees, Evan Palmer-Young
Effects Of Floral Phytochemicals On Growth And Evolution Of A Parasite Of Bumble Bees, Evan Palmer-Young
Doctoral Dissertations
Background: Nectar and pollen are rich in phytochemicals, some of which can reduce disease in pollinators, including agriculturally important honey and bumble bees. Floral phytochemicals could influence the ecological and evolutionary relationships between plants, their pollinators, and parasites that cause pollinator disease. Antiparasitic effects of phytochemicals could be exploited to ameliorate pollinator disease and decline, and thereby sustain pollinator-dependent agricultural production. However, prior studies showed variable effects of phytochemicals on infection in live bees, where differences in bee genotype, abiotic conditions, and parasite strain could influence results. Approach: I used cell cultures of the intestinal trypanosome parasite of bumble bees, …
The Molecular Basis Of Caspase-9 Inactivation By Pka And C-Abl Kinases, Banyuhay Paningbatan Serrano
The Molecular Basis Of Caspase-9 Inactivation By Pka And C-Abl Kinases, Banyuhay Paningbatan Serrano
Doctoral Dissertations
Caspases are the cysteine proteases that facilitate the fundamental pathway of programmed cell death or apoptosis. The activation and function of these powerful enzymes are tightly regulated to ensure the faithful execution of apoptosis and prevent untimely cell death. Many deadly human diseases such as cancer, neurodegeneration and autoimmune disorders have been associated with defective activation and faulty regulation of caspases. As such, caspases are considered as attractive drug targets, which when properly controlled, can lead to effective therapeutics for apoptosis-related diseases. Thus, comprehensive investigations of the structure, function and regulation of caspases are necessary to understand the complex mechanisms …
Light-Harvesting And Light-Responsive Materials For Optoelectronic And Biological Applications, Youngju Bae
Light-Harvesting And Light-Responsive Materials For Optoelectronic And Biological Applications, Youngju Bae
Doctoral Dissertations
In photodynamic therapy, several critical standards are required of photosensitizers including high singlet oxygen quantum yield, biocompatibility in dark, and long term photochemical stability. In addition, current PDT systems lack active targeting strategies to tumor cells, and instead mainly rely on the natural distribution of PS in the body following injection and application of near-infrared light treatment in the tumor region. This thesis describes a series of BODIPY-based molecules that were designed, synthesized and studied as photosensitizers with high singlet oxygen generation capacity through utilizing the heavy atom effect. Additionally, aqueous solubility and active targeting capability were introduced by photosensitizer …
Protein-Nanoparticle Co-Engineering: Self-Assembly, Intracellular Protein Delivery, And Crispr/Cas9-Based Gene Editing, Rubul Mout
Doctoral Dissertations
Direct cytoplasmic delivery of gene editing nucleases such CRISPR/Cas9 systems and therapeutic proteins provides enormous opportunities in curing human genetic diseases, and assist research in basic cell biology. One approach to attain such a goal is through engineering nanotechnological tools to mimic naturally existing intra- and extracellular protein delivery/transport systems. Nature builds transport systems for proteins and other biomolecules through evolution-derived sophisticated molecular engineering. Inspired by such natural assemblies, I employed molecular engineering approaches to fabricate self-assembled nanostructures to use as intracellular protein delivery tools. Briefly, proteins and gold nanoparticles were co-engineered to carry complementary electrostatic recognition elements. When these …