Institutional Repository

The UDSpace Institutional Repository collects and disseminates research material from the University of Delaware.

  • Faculty, staff, and graduate students can deposit their research material directly into UDSpace. Faculty may use UDSpace to fulfill the University of Delaware Faculty Senate Open Access Resolution, and in many cases may use it to fulfill open access requirements from grant funding agencies.
  • Departments can use UDSpace to publish or distribute their working papers, technical reports, or other research material.
  • UDSpace also includes all doctoral dissertations from winter 2014 forward, and all master's theses from fall 2009 forward.

To learn more about UDSpace, and how you can make your research openly accessible to the public, visit our UDSpace Policies website.

 

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Recent Submissions

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2025, 25 Issue, part 2
(Newark, Del.: Chesapeake Pub. Corp., 2025-06-20) Newark post
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2025, 25 Issue, part 1
(Newark, Del.: Chesapeake Pub. Corp., 2025-06-20) Newark post
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THE CHLORIDE TRANSPORT MECHANISM IN THE AVIAN (CHICK) PROXIMAL TUBULE: CFTR CHANNEL AND K+ CHANNEL
(University of Delaware, 2011-05) Varudhini Reddy
In this study, the functional expression of CFTR and the potassium channels, KCNQ1 and KCNN4, were assessed in the avian chick proximal tubule. A primary cell culture model was developed and the apical expression of CFTR in this cell model was revealed using classic electrophysiological methods. A basolateral-permeabilization approach was developed in the lab to permeabilize the basolateral membrane so that the imposed chloride gradients could be observed in this model under the influence of commercial inhibitors. It was found that CFTR-Inh172 and GlyH-101, two CFTR inhibitors, both inhibit secretory chloride gradients (basolateral to apical side). GlyH-101 was found to be the more effective inhibitor. In addition, double inhibitor experiments and a multiple blocker experiment was conducted to examine the expression of potassium channels on the basolateral membrane of the monolayers. In the double inhibitor experiment, clotrimazole was added to either the basolateral side or apical side first, and then added to the opposite side, to observe its effects on Forskolin-activated current. These experiments revealed that clotrimazole, a selective calcium-activated potassium channel blocker, is able to partially inhibit Forskolin-activated current in non-permeabilized monolayers of chick proximal tubules. This suggests that calcium activated potassium channels exist in the proximal tubule. As well, double inhibitor experiments revealed that clotrimazole had a more direct effect on the current when administered to the apical side first. This further suggests that calcium-activated potassium channels may exist on both apical and basolateral sides of the chick proximal tubules.
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ENGINEERING A MICROBIAL CHASSIS FOR NON-STANDARD AMINO ACID BIOSYNTHESIS AND INCORPORATCION
(University of Delaware, 2023-05) Ishika Govil
Genetic code reprogramming augments protein chemistry with non-standard amino acids (nsAAs), enabling the expansion of protein applications as therapeutics, sensors, and biocatalytic tools. Despite this potential of nsAA-containing proteins, major barriers arise for industrial applications of nsAAs: expensive nsAA synthesis and low cellular uptake. One approach to mitigate both of these challenges is to program cells to generate nsAAs intracellularly from inexpensive precursors. A recently characterized class of enzymes, L-threonine transaldolase (TTAs), convert diverse aldehydes to β-hydroxy non-standard amino acids (β-OH-nsAAs), which are nsAAs that contain a hydroxyl substituent at the β-carbon. This study sought to improve β OH-nsAA yield in vivo by engineering a microbial platform in Escherichia coli to stabilize substrate molecules, as well as coupling the TTA with an alcohol dehydrogenase (ADH) and a phosphite dehydrogenase (PTDH), to shift reaction equilibrium. In parallel, this work also assessed the predictive ability of a PyRosetta computational model to design enzymes with high affinity for a β-OH-nsAA substrate.
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Potential Binding Partners of cADPR and cADPR isomers in the Thoeris Phage Defense System
(University of Delaware, 2023-05) Nikhita Bomasamudram
Antibiotics were once hailed as wonder drugs but have led to increased antibiotic resistance. This has become a major global issue, causing millions of deaths annually and higher healthcare costs. The decline in antibiotic discovery and harmful side effects further highlight the need for alternative treatments. Bacteriophage therapy is an alternative approach to combat antibiotic resistance. Bacteriophages are viruses that target and destroy bacteria. Unlike antibiotics, they are highly specific in their infectivity and can coevolve with bacteria, making it harder for resistance to develop. However, challenges include limited host range, safety concerns, regulatory issues, and bacterial anti-phage systems. Understanding these bacterial anti-phage systems is crucial for advancing bacteriophage therapies. The Thoeris System is an novel anti phage system found in bacteria. It relies on two proteins, ThsB and ThsA, to combat phage infections.ThsB detects phages and produces a variant cyclic adenosine diphosphate ribose (cADPR) molecule. ThsA binds to the cADPR which activated its NADase activity, leading to premature bacterial death and phage elimination. The Thoeris System utilizes 2'cADPR and 3'cADPR isomers as signaling molecules. The Thoeris System can be countered by phages with Tad genes that sequester cADPR. The discovery of new anti-phage systems is aided by analyzing defense islands in bacterial genomes. This approach has led to identifying the Thoeris System and other anti-phage systems. ThsC is a novel protein in the Thoeris System, belonging to the HIT protein family. HIT proteins, including Hint1 and E.coli Hint, play roles in cellular immunity and nucleotide hydrolysis. To find the function of ThsC in the Thoeris Systems, cADPR isomers were purified and studied in enzymatic assays with ThsC. Reactions were purified with HPLC and analyzed by Mass Spectrophotometry. The function and role of ThsC still needs to be elucidated in regard to 3’cADPR, ThsA, and ThsB.