Institutional Repository
The UDSpace Institutional Repository collects and disseminates research material from the University of Delaware.
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- 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
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.
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.
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.
2025, 24th Issue, part2
(Newark, Del.: Chesapeake Pub. Corp., 2025-06-13) Newark post
2025, 24th Issue, part1
(Newark, Del.: Chesapeake Pub. Corp., 2025-06-13) Newark post