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Georgia Tech
1.
He, Christine Yi.
Viscous solvents as an environment for nucleic acid replication.
Degree: PhD, Chemical and Biomolecular Engineering, 2017, Georgia Tech
URL: http://hdl.handle.net/1853/59762 
► Many hypotheses concerning the nature of early life assume that genetic information was once transferred through the template-directed synthesis of RNA, prior to the evolution…
(more)
▼ Many hypotheses concerning the nature of early life assume that genetic information was once transferred through the template-directed synthesis of RNA, prior to the evolution of genetically encoded protein synthesis. However, despite more than half a century of research into the chemical origins of nucleic acids, a robust route to the abiotic synthesis of nucleic acid polymers is unclear. In particular, identifying the earliest mechanism for enzyme-free replication of nucleic acids remains an elusive goal. A biophysical problem known as strand inhibition limits copying of a nucleic acid duplex: transferring information from a template sequence in the presence of its complementary strand is inhibited by the stability of the template duplex. Strand inhibition is a major bottleneck in understanding how sustained RNA replication evolved on the early Earth. In this thesis, I describe a robust, prebiotically plausible route to enzyme-free replication of nucleic acids, driven by hot/cool cycles in viscous environments. Viscous solvents enable kinetic trapping of a nucleic acid duplex as single strands, providing a time window for the assembly and ligation of oligonucleotide substrates on the single stranded templates. I have shown that viscous solvents can be utilized to overcome strand inhibition, enabling copying of a gene-length template duplex (>300 nt), a process which is highly unfavorable in aqueous conditions. Additionally, viscosity enables copying of an RNA duplex containing a hammerhead ribozyme motif, suggesting a potential route for the selection and amplification of catalytically active RNA on the prebiotic Earth.
Advisors/Committee Members: Grover, Martha (advisor), Hud, Nicholas (committee member), Styczynski, Mark (committee member), Loren Williams (committee member), Henderson, Clifford (committee member).
Subjects/Keywords: Viscosity; Nucleic acid replication; RNA world; Prebiotic chemistry; Chemical evolution; Origins of life
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APA (6th Edition):
He, C. Y. (2017). Viscous solvents as an environment for nucleic acid replication. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/59762
Chicago Manual of Style (16th Edition):
He, Christine Yi. “Viscous solvents as an environment for nucleic acid replication.” 2017. Doctoral Dissertation, Georgia Tech. Accessed January 26, 2021.
http://hdl.handle.net/1853/59762.
MLA Handbook (7th Edition):
He, Christine Yi. “Viscous solvents as an environment for nucleic acid replication.” 2017. Web. 26 Jan 2021.
Vancouver:
He CY. Viscous solvents as an environment for nucleic acid replication. [Internet] [Doctoral dissertation]. Georgia Tech; 2017. [cited 2021 Jan 26].
Available from: http://hdl.handle.net/1853/59762.
Council of Science Editors:
He CY. Viscous solvents as an environment for nucleic acid replication. [Doctoral Dissertation]. Georgia Tech; 2017. Available from: http://hdl.handle.net/1853/59762
2.
Guerrant, William.
Targeted histone deacetylase inhibition.
Degree: PhD, Chemistry and Biochemistry, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/44907
► Histone deacetylase (HDAC) inhibitors (HDACi) have demonstrated a wealth of biological effects, including anti-proliferative, anti-inflammatory, anti-parasitic, and cognition-enhancing activities. The recent FDA approvals of the…
(more)
▼ Histone deacetylase (HDAC) inhibitors (HDACi) have demonstrated a wealth of biological effects, including anti-proliferative, anti-inflammatory, anti-parasitic, and cognition-enhancing activities. The recent FDA approvals of the inhibitors SAHA and FK-228 have validated HDACi clinical use in cutaneous T cell lymphoma, while numerous clinical trials are currently ongoing using HDACi against a variety of disease states. While the future of the HDAC field looks increasingly promising, there are lingering issues hindering broader use. Recent data point to dysregulation of specific HDAC isoforms in many disease states. However, most current HDACi are pan-inhibitors, lacking the specificity to target individual isoforms. Adding to this, there are currently 18 identified HDAC isoforms, and most lack a defined crystal structure, further complicating the task of designing isoform-specific inhibitors. Most importantly, HDACi have demonstrated a lack of efficacy against solid tumors in the clinic, a major obstacle to broader use in cancer therapy. Several of these issues could more fully be addressed through specific targeting of HDACi, and could bring HDACi into wider and more efficacious pharmaceutical use. Targeting the specific tissue or organelle where HDAC dysregulation occurs could confer greater efficacy in vivo. To this end, we have created four classes of compounds: (1) aryltriazolyl HDACi that potently inhibit HDAC activity and prostate cancer cell growth, (2) dual-targeted inhibitors of Topoisomerase II and HDAC and (3) dual-targeted inhibitors of Topoisomerase I and HDAC, both of which have potent inhibition against both target enzymes as well as cancer cell lines, and finally (4) macrocyclic HDACi that potently inhibit the growth of lung cancer cell lines and preferentially target lung tissue in vivo.
Advisors/Committee Members: Yomi Oyelere (Committee Chair), Donald Doyle (Committee Member), James Powers (Committee Member), Loren Williams (Committee Member), Yuhong Fan (Committee Member).
Subjects/Keywords: HDAC inhibitors; Drug design; Targeted drug delivery; HDAC; Histone deacetylase; Bifunctional inhibitors; Cancer therapy; Drug delivery systems; Cancer Treatment; Enzymes
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APA (6th Edition):
Guerrant, W. (2012). Targeted histone deacetylase inhibition. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/44907
Chicago Manual of Style (16th Edition):
Guerrant, William. “Targeted histone deacetylase inhibition.” 2012. Doctoral Dissertation, Georgia Tech. Accessed January 26, 2021.
http://hdl.handle.net/1853/44907.
MLA Handbook (7th Edition):
Guerrant, William. “Targeted histone deacetylase inhibition.” 2012. Web. 26 Jan 2021.
Vancouver:
Guerrant W. Targeted histone deacetylase inhibition. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Jan 26].
Available from: http://hdl.handle.net/1853/44907.
Council of Science Editors:
Guerrant W. Targeted histone deacetylase inhibition. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/44907
3.
Boz, Mustafa Burak.
Modeling and simulations of single stranded rna viruses.
Degree: PhD, Chemistry and Biochemistry, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/44815
► The presented work is the application of recent methodologies on modeling and simulation of single stranded RNA viruses. We first present the methods of modeling…
(more)
▼ The presented work is the application of recent methodologies on modeling and
simulation of single stranded RNA viruses. We first present the methods of modeling
RNA molecules using the coarse-grained modeling package, YUP. Coarse-grained
models simplify complex structures such as viruses and let us study general behavior of
the complex biological systems that otherwise cannot be studied with all-atom details.
Second, we modeled the first all-atom T=3, icosahedral, single stranded RNA
virus, Pariacoto virus (PaV). The x-ray structure of PaV shows only 35% of the total
RNA genome and 88% of the capsid. We modeled both missing portions of RNA and
protein. The final model of the PaV demonstrated that the positively charged protein N-
terminus was located deep inside the RNA. We propose that the positively charged N-
terminal tails make contact with the RNA genome and neutralize the negative charges in
RNA and subsequently collapse the RNA/protein complex into an icosahedral virus.
Third, we simulated T=1 empty capsids using a coarse-grained model of three
capsid proteins as a wedge-shaped triangular capsid unit. We varied the edge angle and
the potentials of the capsid units to perform empty capsid assembly simulations. The final
model and the potential are further improved for the whole virus assembly simulations.
Finally, we performed stability and assembly simulations of the whole virus using
coarse-grained models. We tested various strengths of RNA-protein tail and capsid
protein-capsid protein attractions in our stability simulations and narrowed our search for
optimal potentials for assembly. The assembly simulations were carried out with two
different protocols: co-transcriptional and post-transcriptional. The co-transcriptional
assembly protocol mimics the assembly occurring during the replication of the new RNA.
Proteins bind the partly transcribed RNA in this protocol. The post-transcriptional
assembly protocol assumes that the RNA is completely transcribed in the absence of
proteins. Proteins later bind to the fully transcribed RNA. We found that both protocols
can assemble viruses, when the RNA structure is compact enough to yield a successful
virus particle. The post-transcriptional protocol depends more on the compactness of the
RNA structure compared to the co-transcriptional assembly protocol. Viruses can exploit
both assembly protocols based on the location of RNA replication and the compactness
of the final structure of the RNA.
Advisors/Committee Members: Stephen C. Harvey (Committee Chair), Adegboyega Oyelere (Committee Member), Loren Williams (Committee Member), Rigoberto Hernandez (Committee Member), Roger Wartell (Committee Member).
Subjects/Keywords: Virus assembly; Coarse-grained models; RNA virus; RNA viruses; RNA; Nucleic acids
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APA (6th Edition):
Boz, M. B. (2012). Modeling and simulations of single stranded rna viruses. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/44815
Chicago Manual of Style (16th Edition):
Boz, Mustafa Burak. “Modeling and simulations of single stranded rna viruses.” 2012. Doctoral Dissertation, Georgia Tech. Accessed January 26, 2021.
http://hdl.handle.net/1853/44815.
MLA Handbook (7th Edition):
Boz, Mustafa Burak. “Modeling and simulations of single stranded rna viruses.” 2012. Web. 26 Jan 2021.
Vancouver:
Boz MB. Modeling and simulations of single stranded rna viruses. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Jan 26].
Available from: http://hdl.handle.net/1853/44815.
Council of Science Editors:
Boz MB. Modeling and simulations of single stranded rna viruses. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/44815
Georgia Tech
4.
Orwig, Susan D.
Biophysical and structural characterization of proteins implicated in glaucoma and Gaucher disease.
Degree: PhD, Chemistry and Biochemistry, 2011, Georgia Tech
URL: http://hdl.handle.net/1853/45816
► The inherited form of primary open angle glaucoma, a disorder characterized by increased intraocular pressure and retina degeneration, is linked to mutations in the olfactomedin…
(more)
▼ The inherited form of primary open angle glaucoma, a disorder characterized by increased intraocular pressure and retina degeneration, is linked to mutations in the olfactomedin (OLF) domain of the myocilin gene. Disease-causing myocilin variants accumulate within trabecular meshwork cells instead of being secreted to the trabecular extracellular matrix thought to regulate aqueous humor flow and control intraocular pressure. Like other diseases of protein misfolding, we hypothesize myocilin toxicity originates from defects in protein biophysical properties. In this thesis, the first preparative recombinant high-yield expression and purification system for the C-terminal OLF domain of myocilin (myoc-OLF) is described. To determine the relative stability of wild-type (WT) and mutant OLF domains, a fluorescence thermal stability assay was adapted to provide the first direct evidence that mutated OLF is folded but less thermally stable than WT. In addition, mutant myocilin can be stabilized by chemical chaperones. Together, this work provides the first quantitative demonstration of compromised stability among identified OLF variants and placing myocilin glaucoma in the context of other complex diseases of protein misfolding.
Subsequent investigations into the biophysical properties of WT myoc-OLF provide insight into its structure and function. In particular, myoc-OLF is stable in the presence of glycosaminoglycans (GAGs), as well as over a wide pH range in buffers with functional groups reminiscent of such GAGs. Myoc-OLF contains significant â-sheet and â-turn secondary structure as revealed by circular dichroism analysis. At neutral pH, thermal melts indicate a highly cooperative transition with a melting temperature of ~55°C. A compact core structural domain of OLF was identified by limited proteolysis and consists of approximately residues 238-461, which retains the single disulfide bond and is as stable as the full myoc-OLF construct. This construct also is capable of generating 3D crystals for structure determination. This data, presented in Chapter 3, inform new testable hypotheses for interactions with specific trabecular extracellular matrix components.
To gain further insight into the biological function of myoc-OLF, a facile fluorescence chemical stability assay was designed to identify possible ligands and drug candidates. In the assay described in Chapter 4, the target protein is initially destabilized with a chemical denaturant and is tested for re-stabilization upon the addition of small molecules. The assay requires no prior knowledge of the structure and/or function of the target protein, and it is amendable to high-throughput screening. Application of the assay using a library of 1,280 compounds revealed 14 possible ligands and drug candidates for myoc-OLF that may also generate insights into myoc-OLF function.
Due to the high â-sheet content of monomeric myoc-OLF and presence of an aggregated species upon myoc-OLF purification, the ability of myoc-OLF to form amyloid fibrils was suspected and…
Advisors/Committee Members: Dr. Raquel Lieberman (Committee Chair), Dr. A. (Yomi) Oyelere (Committee Member), Dr. Al Merril (Committee Member), Dr. Loren Williams (Committee Member), Dr. Nicholas Hud (Committee Member), Dr. Roger Wartell (Committee Member).
Subjects/Keywords: Open-angle glaucoma; Pharmacological chaperones; High-throughput drug screen; Amyloid fibrils; Gaucher disease; Myocilin; Glaucoma; Eye Diseases; Eye Diseases Genetic aspects; Intraocular pressure; Body fluids Pressure; Eye
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APA (6th Edition):
Orwig, S. D. (2011). Biophysical and structural characterization of proteins implicated in glaucoma and Gaucher disease. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45816
Chicago Manual of Style (16th Edition):
Orwig, Susan D. “Biophysical and structural characterization of proteins implicated in glaucoma and Gaucher disease.” 2011. Doctoral Dissertation, Georgia Tech. Accessed January 26, 2021.
http://hdl.handle.net/1853/45816.
MLA Handbook (7th Edition):
Orwig, Susan D. “Biophysical and structural characterization of proteins implicated in glaucoma and Gaucher disease.” 2011. Web. 26 Jan 2021.
Vancouver:
Orwig SD. Biophysical and structural characterization of proteins implicated in glaucoma and Gaucher disease. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Jan 26].
Available from: http://hdl.handle.net/1853/45816.
Council of Science Editors:
Orwig SD. Biophysical and structural characterization of proteins implicated in glaucoma and Gaucher disease. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/45816
5.
Shaffer, Hally A.
Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation.
Degree: PhD, Chemistry and Biochemistry, 2011, Georgia Tech
URL: http://hdl.handle.net/1853/39620
► Nuclear receptors are ligand-activated transcription factors that play significant roles in various biological processes within the body, such as cell development, hormone metabolism, reproduction, and…
(more)
▼ Nuclear receptors are ligand-activated transcription factors that play significant roles in various biological processes within the body, such as cell development, hormone metabolism, reproduction, and cardiac function. As transcription factors, nuclear receptors are involved in many diseases, such as diabetes, cancer, and arthritis, resulting in approximately 10-15% of the pharmaceutical drugs presently on the market being targeted toward nuclear receptors. Structurally, nuclear receptors consist of a DNA-binding domain (DBD), responsible for binding specific sequences of DNA called response elements, fused to a ligand-binding domain (LBD) through a hinge region. The LBD binds a small molecule ligand. Upon ligand binding, the LBD changes to an active conformation leading to the recruitment of coactivator (CoAC) proteins and initiation of transcription. As a result of their involvement in disease, there is an emphasis on engineering nuclear receptors for applications in gene therapy, drug discovery and metabolic engineering.
Advisors/Committee Members: Bahareh Azizi (Committee Chair), Donald Doyle (Committee Chair), Andreas Bommarius (Committee Co-Chair), Loren Williams (Committee Co-Chair), Adegboyega Oyelere (Committee Member), Nick Hud (Committee Member), Sheldon May (Committee Member).
Subjects/Keywords: Nuclear receptors; Chemical complementation; Negative chemical complementation; Yeast-two hybrid selection; Pregnane X receptor; Estrogen receptor; Pregnane; Protein engineering; Nuclear receptors (Biochemistry); Transcription factors; Yeast Genetics
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APA (6th Edition):
Shaffer, H. A. (2011). Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/39620
Chicago Manual of Style (16th Edition):
Shaffer, Hally A. “Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation.” 2011. Doctoral Dissertation, Georgia Tech. Accessed January 26, 2021.
http://hdl.handle.net/1853/39620.
MLA Handbook (7th Edition):
Shaffer, Hally A. “Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation.” 2011. Web. 26 Jan 2021.
Vancouver:
Shaffer HA. Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation. [Internet] [Doctoral dissertation]. Georgia Tech; 2011. [cited 2021 Jan 26].
Available from: http://hdl.handle.net/1853/39620.
Council of Science Editors:
Shaffer HA. Engineering the pregnane X receptor and estrogen receptor alpha to bind novel small molecules using negative chemical complementation. [Doctoral Dissertation]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/39620
Georgia Tech
6.
Marotta, Nicole Ella.
Patterned nanoarray sers substrates for pathogen detection.
Degree: PhD, Chemistry and Biochemistry, 2010, Georgia Tech
URL: http://hdl.handle.net/1853/37274
► The objectives of the work presented were to 1) fabricate reproducible nanorod array SERS substrates, 2) detection of bacteria using nanorod substrates, 3) detection of…
(more)
▼ The objectives of the work presented were to 1) fabricate reproducible nanorod array SERS substrates, 2) detection of bacteria using nanorod substrates, 3) detection of DNA hybridization using nanorod substrates and 4) critically evaluate the sensing method.
Important findings from this work are as follows. A novel method for batch fabrication of substrates for surface enhanced Raman scattering (SERS) has been developed using a modified platen machined to fit in a commercial electron beam evaporator. The use of this holder enables simultaneous deposition of silver nanorod (AgNR) arrays onto six microscope slide substrates utilizing glancing angle deposition. In addition to multiple substrate fabrication, patterning of the AgNR substrates with 36 wells allows for physical isolation of low volume samples. The well-to-well, slide-to-slide, and batch-to-batch variability in both physical characteristics and SERS response of substrates prepared via this method was nominal. A critical issue in the continued development of AgNR substrates is their stability over time, and the potential impact on the SERS response. The thermal stability of the arrays was investigated and changes in surface morphology were evaluated using scanning electron microscopy and x-ray diffraction and correlated with changes in SERS enhancement. The findings suggest that the shelf-life of AgNR arrays is limited by migration of silver on the surface. Continued characterization of the AgNR arrays was carried out using fluorescent polystyrene microspheres of two different sizes. Theory suggests that enhancement between nanorods would be significantly greater than at the tops due to contributing electromagnetic fields from each nanostructure. In contrast to the theory, SERS response of microspheres confined to the tops of the AgNR array was significantly greater than that for beads located within the array. The location of the microspheres was established using optical fluorescence and scanning electron microscopy.
The application of SERS to characterizing pathogens such as bacteria and viruses is an active area of investigation. AgNR array-based SERS substrates have enabled detection of pathogens present in biofluids. Specifically, several publications have focused on determining the spectral bands characteristic of bacteria from different species and cell lines. Studies were carried out on three strains of bacteria as well as the medium in which the bacteria were grown. The spectra of the bacteria and medium were surprisingly similar, so additional spectra were acquired for commonly used bacterial growth media. In many instances, these spectra were similar to published spectra purportedly characteristic of specific bacterial species.
In addition to bacterial samples, nucleic acid hybridization assays were investigated. Oligonucleotide pairs specifically designed to detect respiratory syncytial virus (RSV) in nasal fluids were prepared and evaluated. SERS spectra acquired on oligos, alone or in combination, contain the…
Advisors/Committee Members: Lawrence Bottomley (Committee Chair), Julia Kubanek (Committee Member), L. Andrew Lyon (Committee Member), Loren Williams (Committee Member), Mostafa El-Sayed (Committee Member).
Subjects/Keywords: Silver nanostructure; Surface enhanced Raman scattering; Silver nanorod array; Surface enhanced Raman spectroscopy; Oblique angle deposition; Glancing angle deposition; SERS substrate; Raman effect; Raman spectroscopy
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APA (6th Edition):
Marotta, N. E. (2010). Patterned nanoarray sers substrates for pathogen detection. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/37274
Chicago Manual of Style (16th Edition):
Marotta, Nicole Ella. “Patterned nanoarray sers substrates for pathogen detection.” 2010. Doctoral Dissertation, Georgia Tech. Accessed January 26, 2021.
http://hdl.handle.net/1853/37274.
MLA Handbook (7th Edition):
Marotta, Nicole Ella. “Patterned nanoarray sers substrates for pathogen detection.” 2010. Web. 26 Jan 2021.
Vancouver:
Marotta NE. Patterned nanoarray sers substrates for pathogen detection. [Internet] [Doctoral dissertation]. Georgia Tech; 2010. [cited 2021 Jan 26].
Available from: http://hdl.handle.net/1853/37274.
Council of Science Editors:
Marotta NE. Patterned nanoarray sers substrates for pathogen detection. [Doctoral Dissertation]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/37274
Georgia Tech
7.
Horowitz, Eric D.
Intercalator-mediated assembly of nucleic acids.
Degree: PhD, Chemistry and Biochemistry, 2009, Georgia Tech
URL: http://hdl.handle.net/1853/33937
► The RNA World hypothesis suggests that RNA, or a proto-RNA, existed in an early form of life that had not yet developed the ability to…
(more)
▼ The RNA World hypothesis suggests that RNA, or a proto-RNA, existed in an early form of life that had not yet developed the ability to synthesize protein enzymes. This hypothesis, by some interpretations, implies that nucleic acid polymers were the first polymers of life, and must have therefore spontaneously formed from simple molecular building blocks in the "prebiotic soup." Although prebiotic chemists have searched for decades for a process by which RNA can be made from plausible prebiotic reactions, numerous problems persist that stand in the way of a chemically-sound model for the spontaneous generation of an RNA World (e.g., strand-cyclization, heterogeneous backbones, non-selective ligation of activated nucleotides). The Molecular Midwife hypothesis, proposed by Hud and Anet in 2000, provides a possible solution to several problems associated with the assembly of the first nucleic acids. In this hypothesis, nucleic acid base pairs are assembled by small, planar molecules that resemble molecules which are known today to intercalate the base pairs of nucleic acid duplexes. Thus, the validity and merits of the Molecular Midwife hypothesis can be, to some extent, explored by studying the effects of intercalation on the non-covalent assembly of nucleic acids.
In this thesis, I explore the role of the sugar-phosphate backbone in dictating the structure and thermodynamics of nucleic acid intercalation by using 2′,5′-linked RNA intercalation as a model system of non-natural nucleic acid intercalation. The solution structure of an intercalator-bound 2′,5′ RNA duplex reveals structural and thermodynamic aspects of intercalation that provide insight into the origin of the nearest-neighbor exclusion principle, a principle that is uniformly obeyed upon the intercalation of natural (i.e. 3′,5′-linked) RNA and DNA. I also demonstrate the ability of intercalator-mediated assembly to circumvent the strand-cyclization problem, a problem that otherwise greatly limits the polymerization of short oligonucleotides into long polymers. Together, the data presented in this thesis illustrate the important role that the nucleic acid backbone plays in governing the thermodynamics of intercalation, and provide support for the proposed role of intercalator-mediated assembly in the prebiotic formation of nucleic acids.
Advisors/Committee Members: Nicholas V. Hud (Committee Chair), David Sherrill (Committee Member), Loren Williams (Committee Member), Roger Wartell (Committee Member), Steve Harvey (Committee Member).
Subjects/Keywords: RNA; Intercalation; DNA; Nucleic acids; Origin of life; Template-directed synthesis; Life Origin; Oligonucleotides; Proteins Synthesis; Proteins
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APA (6th Edition):
Horowitz, E. D. (2009). Intercalator-mediated assembly of nucleic acids. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/33937
Chicago Manual of Style (16th Edition):
Horowitz, Eric D. “Intercalator-mediated assembly of nucleic acids.” 2009. Doctoral Dissertation, Georgia Tech. Accessed January 26, 2021.
http://hdl.handle.net/1853/33937.
MLA Handbook (7th Edition):
Horowitz, Eric D. “Intercalator-mediated assembly of nucleic acids.” 2009. Web. 26 Jan 2021.
Vancouver:
Horowitz ED. Intercalator-mediated assembly of nucleic acids. [Internet] [Doctoral dissertation]. Georgia Tech; 2009. [cited 2021 Jan 26].
Available from: http://hdl.handle.net/1853/33937.
Council of Science Editors:
Horowitz ED. Intercalator-mediated assembly of nucleic acids. [Doctoral Dissertation]. Georgia Tech; 2009. Available from: http://hdl.handle.net/1853/33937
Georgia Tech
8.
Capadona, Jeffrey R.
Surface-directed assembly of fibrillar extracellular matrices.
Degree: PhD, Chemistry and Biochemistry, 2005, Georgia Tech
URL: http://hdl.handle.net/1853/10575
► Biologically-inspired materials have emerged as promising substrates for enhanced repair in various therapeutic and regenerative medicine applications, including nervous and vascular tissues, bone, and cartilage.…
(more)
▼ Biologically-inspired materials have emerged as promising substrates for enhanced repair in various therapeutic and regenerative medicine applications, including nervous and vascular tissues, bone, and cartilage. These strategies focus on the development of materials that integrate well-characterized domains from biomacromolecules to mimic individual functions of the extracellular matrix (ECM), including cell adhesive motifs, growth factor binding sites, and protease sensitivity. A vital property of the ECM is the fibrillar architecture arising from supramolecular assembly. For example, the fibrillar structure of fibronectin (FN) matrices modulates cell cycle progression, migration, gene expression, cell differentiation, and the assembly of other matrix proteins. Current biomaterials do not actively promote deposition and assembly of ECM. In this research, we describe the rational design and investigation of non-fouling biomimetic surfaces in which an oligopeptide sequence (FN13) from the self-assembly domain of FN is tethered to non-fouling substrates. This surface modification directs cell-mediated co-assembly of robust fibrillar FN and type I collagen (COL) matrices reminiscent of ECM, and increases in cell proliferation rates. Furthermore, the effect of this peptide is surface-directed, as addition of the soluble peptide has no effect on matrix assembly. We have also identified a critical surface density of the immobilized peptide to elicit the full activity. These results contribute to the development and design of biomimetic surface modifications that direct cell function for biomedical and biotechnology applications.
Advisors/Committee Members: Andres J. Garcia (Committee Chair), David M. Collard (Committee Chair), Elliot Chaikof (Committee Member), Loren Williams (Committee Member), Marcus Weck (Committee Member).
Subjects/Keywords: Fibronectin; Biomimetics; Biomaterials; Extracellular matrices; Self-assembled monolayers
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APA (6th Edition):
Capadona, J. R. (2005). Surface-directed assembly of fibrillar extracellular matrices. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/10575
Chicago Manual of Style (16th Edition):
Capadona, Jeffrey R. “Surface-directed assembly of fibrillar extracellular matrices.” 2005. Doctoral Dissertation, Georgia Tech. Accessed January 26, 2021.
http://hdl.handle.net/1853/10575.
MLA Handbook (7th Edition):
Capadona, Jeffrey R. “Surface-directed assembly of fibrillar extracellular matrices.” 2005. Web. 26 Jan 2021.
Vancouver:
Capadona JR. Surface-directed assembly of fibrillar extracellular matrices. [Internet] [Doctoral dissertation]. Georgia Tech; 2005. [cited 2021 Jan 26].
Available from: http://hdl.handle.net/1853/10575.
Council of Science Editors:
Capadona JR. Surface-directed assembly of fibrillar extracellular matrices. [Doctoral Dissertation]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/10575
. 
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