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Articles 1 - 7 of 7
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Investigating The Role Of Tryptophan In The Native Photo-Crosslinking Of A Cys-Containing Transmembrane Helix To A Membrane Lipid Double Bond, Michael Jay Telehany
Investigating The Role Of Tryptophan In The Native Photo-Crosslinking Of A Cys-Containing Transmembrane Helix To A Membrane Lipid Double Bond, Michael Jay Telehany
Undergraduate Honors Theses
Our research group has previously discovered that a Cys residue within a transmembrane (TM) helix can directly photo-crosslink to a membrane lipid via an oxythiolation addition reaction to the double bond within the lipid, with a reaction yield of 10-20%. The pH-low Insertion Peptide (pHLIP) serves as our model TM helix, while the POPC lipid bilayer is our model membrane. We had long believed that the Trp residues within the sequence of pHLIP served as the key chromophore for this reaction, and thus they were essential for the formation of the TM helix-lipid adduct. To test this hypothesis, I synthesized …
The Synthesis Of 3-Formyltyrosine For The Purpose Of In Virto Fluorescent Visualization Of Microtubules, Angelina Bonacasa
The Synthesis Of 3-Formyltyrosine For The Purpose Of In Virto Fluorescent Visualization Of Microtubules, Angelina Bonacasa
Undergraduate Honors Theses
Microtubules and the desire to visualize them has been of utmost importance in understanding the behavior of the cytoskeleton. Even further, scientists are using this knowledge to elucidate cancerous activities as they occur within cells. In order to acquire this knowledge, the following methods have been established: the expression of tubulin after it has been fused with a fluorescent protein, the insertion of tubulin that has been exogenously labeled, and the use of fluorescent-probe conjugated microtubule ligands, such as paclitaxel. These methods, however, tend to distort the protein’s native function, thereby preventing an accurate analysis. This concern drives the need …
Computational Investigation Of Calmodulin Photocontrol With The Help Of An Azobenzene Derivative, Jeremy Wells
Computational Investigation Of Calmodulin Photocontrol With The Help Of An Azobenzene Derivative, Jeremy Wells
Undergraduate Honors Theses
The ability to control the activity and binding capability of enzymes in a reversible manner offers tremendous control over biological processes. Photocontrol, in particular, is promising in that electromagnetic radiation can be fine-tuned in terms of its strength, location, and duration. Photosensitive compounds, such as the azobenzene family, experience an isomerization at certain wavelengths, and attaching these compounds to enzymes has the potential to alter their structure and activity. Calmodulin (CaM) is a Ca2+ -sensitive signaling protein that has the ability to affect several downstream processes in eukaryotes and is an excellent target for photocontrol due to its small size …
Glypro As A Self-Immolative Spacer For The Release Of Payloads From Antibody-Drug Conjugates, Justin Michael Howe
Glypro As A Self-Immolative Spacer For The Release Of Payloads From Antibody-Drug Conjugates, Justin Michael Howe
Undergraduate Honors Theses
Antibody-drug conjugates (ADCs) are an increasingly popular modality for targeted drug delivery in many oncological and immunological applications. The paratope of a monoclonal antibody (mAb) directs the delivery of a conjugated therapeutic payload to antigen expressing cells, resulting in a controlled transport of payload to a desired cell type. Internalization of the ADC followed by lysosomal degradation results in the release of a payload to perform its biochemical function. A chemical linker between the drug and the antibody is responsible for the stability of the conjugate in circulation alongside mediating the release of an unmodified payload under lysosomal conditions. Currently, …
Electrophysiological Characterization Of The Inhibitory Effects Of 2-Amino-4-Bis (Aryloxy Benzyl) Amino Butanoic Acids On Alanine Serine Cysteine Transporter 2 And Sodium Coupled Neutral Amino Acid Transporter 2, Paul Serguei Zakrepine
Electrophysiological Characterization Of The Inhibitory Effects Of 2-Amino-4-Bis (Aryloxy Benzyl) Amino Butanoic Acids On Alanine Serine Cysteine Transporter 2 And Sodium Coupled Neutral Amino Acid Transporter 2, Paul Serguei Zakrepine
Undergraduate Honors Theses
Alanine Serine Cysteine Transporter 2 (ASCT2) is a member of the solute carrier 1A (SLC1A) family of transport proteins. It is a Na+ dependent, obligatory neutral amino acid exchanger with the capability to transport glutamine and it is a primary glutamine transport protein in cancer cells. This glutamine transport capability confers an important physiological role for ASCT2 in the maintenance of intracellular amino acid pools for various metabolic and cell signaling pathways. Because of this, ASCT2 is found to be overexpressed in many cancers, which rely heavily on glutamine as an essential nutrient for cell survival and growth. A wealth …
Optimization Of Adc Linkers: Design And Evaluation Of A Fret-Based Adc Linker-Library, Jared T. Miller
Optimization Of Adc Linkers: Design And Evaluation Of A Fret-Based Adc Linker-Library, Jared T. Miller
Undergraduate Honors Theses
Success of Antibody-drug conjugates (ADCs) relies on the maintained integrity of a chemical linker fusing a therapeutic payload to a monoclonal antibody. Recent reports have revealed the lead linker ValCitPABC has poor stability in rodent models compared to mammalian counterparts, resulting in many clinical investigations predicting poorer ADC efficacy due to premature payload release in these model systems. Optimization of this chemical linker to be resistant both in mouse and human models would streamline ADC progression into clinical trials. Herein we describe the synthesis and development of a FRET-based assay for evaluating linker stability in vitro. Evaluation of lysosomal release …
The Role Of Criticality Of Gene Regulatory Networks On Emergent Properties Of Biological Systems, Hyobin Kim
The Role Of Criticality Of Gene Regulatory Networks On Emergent Properties Of Biological Systems, Hyobin Kim
Graduate Dissertations and Theses
The relationship between criticality of gene regulatory networks (GRNs) and dynamics of GRNs at a single cell level has been vigorously studied. However, the relationship between the criticality of GRNs and properties of multicellular organisms at a higher level has not been fully explored. Here we aim at revealing potential roles of the criticality of GRNs at a multicellular and hierarchical level, using a random Boolean network as a GRN. We perform three studies. Firstly, we propose a GRN-based morphogenetic model, and delve into the role of the criticality of GRNs in morphogenesis at a multicellular level. Secondly, we include …