Alzheimer’s disease (AD) is ranked as the seventh leading cause of death in the US with over 6 million Americans currently diagnosed, and that number is projected to reach about 13 million by 2050. AD is currently believed to be caused by numerous factors ranging from genetics, lifestyle, and environmental conditions. The exact pathogenesis of AD remains uncertain, but the pathology of the disease includes the presence of amyloid beta (Aβ) plaques and neurofibrillary tangles composed of the protein tau in the brain. These are two proteins are normally found in the brains of healthy individuals, but amyloid-beta peptides are often degraded under normal conditions, while tau plays a role in stabilizing our cell’s cytoskeletal structures. In Alzheimer’s however, these proteins are misfolded and accumulate, causing disruptions in cell signaling and neuronal death, therefore worsening the disease. Aβ plaques also activate microglial cells, which produce cytokines and induce inflammation. Cytokines are signaling molecules produced by immune cells that mediate inflammatory signaling. Activation of an inflammasome complex found in microglial cells, NLRP3, leads to the production of the cytokine IL-1β which has been implicated in Alzheimer’s due to its ability to induce and maintain this chronic cycle of inflammation, and possibly results in more amyloid-beta deposition. Our research looks into the mode of action of novel anti-inflammatory drugs and their potential to reduce inflammation at the level of the NLRP3 inflammasome as a mechanism to slow down the progression of AD.
 

Alzheimer’s disease is the most common form of dementia and affects over 6 million Americans 65 and older. In the absence of a cure, addressing modifiable risk factors could potentially reduce the risk of AD development. There is an established relationship between diet and AD risk. For example, studies in rodents found that highly processed Western diets are associated with cognitive impairment and increased amyloid-beta in the hippocampus, a brain region critical for learning and memory. Conversely, plant-based diets like the Mediterranean diet (MD) have been shown to protect against cognitive impairment.

A key limitation in the scientific literature is that most animal studies have only examined the effects of extremely high-fat WD (providing over 40-60% kcal from fat), or a MD with only one or two key nutritional components. We aimed to fill a gap in the literature by designing a rodent diet that mimicked the typical American diet (TAD), rather than an exaggerated WD, and a macronutrient-matched MD. C57BL/6J mice were weaned onto one of the two diets at postnatal day 21. Following six months of diet, we conducted behavioral tests, including open field, elevated zero, and object-location memory task (OLMT). In comparison to the MD, mice consuming the TAD had decreased locomotor activity and exploratory behavior, increased anxiety-like behavior, and reduced spatial memory.

Mercury contamination is of increasing concern. As the earth’s temperature continues to rise, it is vital to study the trends of MeHg absorption. Continuing to gather MeHg absorption data in the Northwest part of Greenland will help to grow our understanding of MeHg trends in Arctic territories. This study will increase the amount of data collected on MeHg levels, allowing a more accurate comparison between MeHg level patterns and species behavior, breeding success, and death rates in Arctic bird species (Chastel et al., 2022). Understanding how MeHg contamination affects health and prosperity is critical, not only for the environment and animals but people as well, as these birds are often part of the native Greenlander diet (Hong et al. 2012; Johansen et al. 2004). Temporal monitoring is also highly beneficial for evaluating the efficacy of policies aiming to reduce anthropogenic Hg emissions (AMAP 2021).

Pyridinophane molecules have recently been shown to have both antioxidant and pharmacological properties suitable for therapeutic applications targeting neurodegenerative diseases, including Alzheimer’s Disease. We have synthesized derivatives of this parent molecule with added moiety substitutions. These substitutions are designed to enhance the permeability and antioxidant activity beyond that of the parent molecule in the hopes of producing a molecule suitable for pharmacological testing in animal models. To establish a principle between moiety location on the parent molecule and its activity, we have placed 8-hydroxyquinoline, a moiety established in our lab to improve the antioxidant activity of parent molecules, in varying locations. The results presented here will detail our evaluation of the substitution of 8-hydroxyquinoline in varying locations and its impact on the molecule’s permeability and reactivity through a series of statistics, including a DPPH assay, determination of logBB, and the determination of chelating equilibrium quotients at varying pH (“log beta”).

Alzheimer’s Disease (AD) affects over 6.5 million Americans over the age of 65. Previous research links AD with Amyloid-Beta-40 (AB40) aggregation in the brain, which creates neurotoxic plaques, associated with AD. A potential mechanism in the treatment of AD is using therapeutics that will prevent the formation of these plaques, which is possible with Metal Chelation Therapy.
Metal ion chelation ideally stops metal ions from aiding in the aggregation of AB40. However, to deliver metal chelating agents to the brain, a drug-delivery mechanism is required that will be able to deliver this medicine across the Blood-Brain Barrier. Porous silica is a potential drug delivery material due to its small particle size, high loading capacity, surface tunability, and biocompatibility. Along with these characteristics, porous silica can create a “sustained” release of a given drug, allowing for a slow and steady release profile, reducing the risks of medication side effects.
This project seeks to establish the optimal loading capacities of a class of potential metal ion chelate therapeutic molecules known as pyclens into porous silica, each with different pyridyl moieties and chemical functionalities along the rim of the molecule. Encapsulation efficiencies measurements for these pyclen derivatives reveal loading percentages in the 10-19% range, varying by pyclen identity. Additionally, release studies monitored diffusion over time to find which pyclen molecule achieved “sustained” release. All loaded pyclen species were able to show sustained release after 20 minutes, both in the presence and absence of copper (II) ions. Turbidity assays with AB40 present showed that all pyclen species decreased protein aggregation in the presence of copper (relative to non-pyclen controls), showing that all pyclen species were able to successfully prevent the aggregation of AB40 in the presence of copper.
Release studies in a more authentic BBB model remain to be completed.

Polyvinyl pyrrolidone (PVP) is a nonionic synthetic polymer often employed in drug formulations. Due to its hydrophilicity, it is often found in aqueous solutions where it can act as a solubilizing agent for organic molecules with poor water solubility. Interestingly, PVP also exhibits fluorescence in water. Furthermore, PVP fluorescence intensity is known to decrease as the concentration of salt increases. This effect has been attributed to the affinity of inorganic anions to PVP chains. In this poster, we examine the effect of an anionic surfactant, sodium dodecyl sulfate (SDS), on PVP fluorescence. In contrast with inorganic anions, we found that PVP fluorescence intensity increases with SDS concentration. We attribute this effect to the binding of SDS anions to PVP chains. This hypothesis is supported by a crystallization assay showing that PVP suppresses formation of SDS crystals. Our experimental results indicate that PVP fluorescence could be used to determine concentration of other types of anionic surfactants in water. These include perfluoroalkyl substances (PFAS), which are relevant environmental chemistry.

Protein purification is a critical step in the downstream processing of protein. Although chromatography is the most employed technique for protein purification, novel strategies that reduce operational costs and increase the amount of purified protein are being developed. These strategies have the possibility to reduce the price of protein-based pharmaceutical and biotechnological products through the reduction of purification cost. Preparative protein crystallization is one such economically-sustainable alternative to chromatography, however protein crystallization is very slow and is difficult to implement in current protein purification protocols. In our lab, we explore the use of metastable liquid-liquid phase separation (LLPS) to enhance protein crystallization. LLPS is typically induced by cooling protein aqueous samples below a well-defined temperature, called the LLPS temperature. We have previously shown that cooling aqueous samples of lysozyme in the presence of NaCl (0.15 M) and HEPES (0.10 M, pH 7.4) below LLPS temperature reproducibly produces yields of lysozyme crystallization above 90%. However, this process requires sample cooling to relatively low temperatures
(below –10 °C). In this poster, we examine the use of polyethylene glycol (PEG) as an additive that increases LLPS temperature. Our experimental results show that PEG increases LLPS temperature without appreciably altering formation of lysozyme crystals. The effect of PEG concentration on LLPS temperature is explained by considering the mechanism of macromolecular crowding.

The goal of this project is to develop synthetic riboswitches for trimethylamine N-oxide
(TMAO). TMAO has been shown to regulate various physiological processes involved in the
development of atherosclerosis. A riboswitch is a non-coding RNA molecule that specifically
binds to a ligand and thereby controls the expression of genes in the downstream. A synthetic
riboswitch for TMAO could be useful for regulating gene expression in response to TMAO and
detecting TMAO in complex biological samples such as urine and blood. The 17 nucleotides in
the aptamer domain of a naturally occurring glycine riboswitch were randomized to generate a
library containing billions of different variants. The library was placed in the upstream of the
cat-upp fusion gene for a series of dual genetic selections. The positive selection is done in the
presence of TMAO to identify functional riboswitches that make cells resistant to
chloramphenicol. The negative selection is performed in the presence of 5-fluorouracil to kill
the cells containing the riboswitch variants activated by any endogenous molecules. Once
identified by several rounds of dual genetic selections, the synthetic TMAO riboswitches will
be tested by colorimetric and fluorescence assays.

Chirality is a property of two molecules of the same composition to not be structurally superimposable on each other. Chiral structures are both common and essential throughout nature. Porous material can be used as templates for creating chirality. The use of cellulose as a template provides environmentally friendly alternatives for templating chirality onto materials such as silica. New research in this field includes using chiral silica templates for the synthesis of chiral perovskite films, a semiconductor material with bright light emission found in light sources like light emitting diodes (LEDs).

This project began by testing cellulose obtained from several different vendors to determine which product has the ideal properties for use in chiral films. An important aspect of cellulose product is its relative acidity/basicity (quantified in terms of pH), which can be regulated to control the degradation of cellulose into nanocrystals as well as the formation of chiral structures. Initially, the cellulose was acidified using sulfuric acid which causes aggregation and kinetic arrest within particles. A technique known as ion exchange chromatography is now being used in these experiments as the method of choice for acidifying cellulose samples.

The time allotted for cellulose nanocrystals to obtain chiral conformation is also an important aspect of creating chiral films. Initially, samples were not left to stand motionless and were immediately converted into silica films. Currently however, our procedure has been modified to allow the chiral cellulose nanocrystals at least seven days of sitting undisturbed before the addition of a silica precursor molecule, thereby facilitating the chiral product from the rest of the product mixture. Upon successful isolation of chiral cellulose-silica films, experiments will be initiated to template the formation of chiral light-emitting perovskite structures by infiltration.

Texas Christian University’s Chemistry Club has always made a conscious effort to interest and include first year students through events and volunteering. This year’s project was focused on boosting numbers and cultivating a stronger community within the Chemistry and Biochemistry Department by specifically holding events to engage first year students. Events included the citrus social, periodic table of cupcakes, murder mystery play, tie dye event, and jeopardy night. This gave students a chance to get to know their peers better, to interact with a wide range of professors, and to gain knowledge about chemistry from outside the classroom. The success of these events has lead to record high attendance not only for the events but also for the Chemistry Club meetings held bi-weekly. The success of this initiative will ensure these and other events will be hosted for years to come, hopefully growing to the size where other schools can join and collaborate, further building a community within the field of chemistry and biochemistry.