Invasive species harm local ecosystems, economies, and cultures. There has been a substantial effort to research the recent increase in the number and frequency of successful invaders; however, relatively little information regarding if and to what extent genetics influences a species ability to become a successful invader exists. Whole genome sequencing provides a mechanism that could illuminate the importance of genetics for successful invasion and uncover the roles selection plays in predisposing populations to be successful invaders. Northern pike (Esox lucius) are native to the Holarctic region but have been widely introduced across Europe and North America. For example, pike were introduced to the area around Anchorage, Alaska in the 1970s and have since spread throughout southcentral Alaska. This species represents a major threat to populations of native fish species, especially multiple species of salmonid. Current management efforts appear to fall short as many pike populations have increased following removal. Part of this growth is likely from the ability of pike to disperse into marine environments, allowing them to colonize new bodies of freshwater. However, whether this ability to disperse is genetic – and therefore heritable - remains unknown. If there are alleles that predispose some populations of pike to be successful invaders, then such populations should be the target of multifaceted eradication efforts. To that end, several populations of pike – consisting of known residents and dispersers - from south-central Alaska were analyzed using whole genome sequencing to a) determine if there are alleles associated with dispersal ability and b) to determine if and to what extent populations are predisposed to dispersal behaviors. Overall, this research will improve our understanding of the genetic basis of invasive biology, identify populations of pike that should become a priority for eradication, and help protect native fish species.

“EVALUATING THE EFFECT OF NOVEL DRUGS ON LPS-INDUCED INFLAMMATION USING ENZYME-LINKED IMMUNOSORBENT ASSAY”

Neuroinflammation plays a key role in many neurodegenerative diseases and is characterized by the over-activation of immune cells within the central nervous system. Activated microglia and astrocytes release pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF- α), as well as reactive oxygen species that contribute to neuronal damage. These inflammatory responses are mediated through signaling pathways including the NF-κB pathway and the NLRP3 inflammasome.
Alzheimer’s disease (AD) is the most common neurodegenerative disease and the leading cause of dementia worldwide. In AD, accumulation of β-amyloid plaques (Aβ) stimulates chronic neuroinflammatory responses and contributes to neuronal dysfunction and disease progression. Elevated levels of inflammatory cytokines, particularly IL-1β, have been strongly associated with Aβ plaque deposition and the onset of AD.
Based on this relationship, targeting neuroinflammatory signaling pathways might be a promising therapeutic strategy for AD. PD2244, a novel compound synthesized by P2D Biosciences, is hypothesized to reduce neuroinflammation by suppressing the production of pro-inflammatory cytokines involved in AD pathology. Specifically, PD2244 is expected to decrease IL-1β production by inhibiting either the NF-κB pathway or the NLRP3 inflammasome.
To test this hypothesis, PD2244 was tested on several cells related to AD pathology, including microglial, neuronal, and monocytic. These cells were pretreated with increasing concentrations of PD2244 prior to inflammatory stimulation. IL-1β production was quantified using Enzyme Linked Immunosorbent Assay (ELISA), a highly sensitive technique commonly used to detect pro-inflammatory cytokine production.

As antibiotic resistance continues to rise, the development of new antibiotics is more important than ever. However, converting an active antibiotic compound into a clinically viable pharmaceutical requires optimization of the drug’s pharmacokinetic profile, including improving its stability, permeability, and targeted delivery to pathogens. One strategy to overcome these delivery challenges is the use of prodrugs—inactive or chemically modified derivatives of a parent compound that are converted to their active form in vivo, most often through enzymatic cleavage. Effective prodrug modifications can improve drug delivery to pathogens or enhance permeability through the hydrophobic bacterial cell membrane while maintaining or improving the activity of the parent compound. Our goal is to categorize novel prodrug structures by assessing efficacy of penicillin prodrug derivatives. This project analyzes the activity of penicillin prodrugs synthesized in the Montchamp Lab against the gram-positive bacterial species Bacillus anthracis and vancomycin-resistant Enterococcus faecalis using MIC (Minimum Inhibitory Concentration) assays. Penicillin G is a well-known antibiotic with a single acidic site, providing a convenient parent compound for synthesis and well-established MIC values. We determined that, consistent with hypothesis, prodrug structures with increasing numbers of enzymatic activation “triggers” exhibited increased antibiotic activity. For example, structures containing two benzene groups showed greater activity than those containing one, and both showed greater activity than nonderivatized Penicillin G. Knowledge of these promising prodrug structures will guide the future synthesis of antibiotics with more challenging pharmacokinetics to improve drug delivery and efficacy.

Partner and Localizer of BRCA2 (PALB2) is a necessary linker protein between BRCA1 and BRCA2 that directs the cells towards homologous recombination in the presence of double-strand breaks (DSB). When this linkage is disrupted, the cell routes the repair towards non-homologous end joining or single-stranded annealing, which are not as efficient or accurate in their repair of DSB. With inefficient DNA repair, mutations accumulate that increase the risk of the development of cancer. It has been documented that mutation L35P in PALB2 is pathogenic and leads to a decrease in HR in cells. However, it is unknown if the loss of leucine at this position is causing a decrease in BRCA1 binding or if it is the introduction of a proline into the coiled coil region that is disrupting the secondary structure, thereby inhibiting binding. We are studying 5 variants of unknown significance (VUS) from PALB2 that are within the coiled coil and are also proline substitutions. One of these mutations is within the binding interface and the other four are on the backside of the coil opposite the predicted binding interface. We aim to answer if it is the introduction of a proline that is destroying the secondary structure and preventing binding. Isothermal titration calorimetry data suggests that all proline variants thus far, regardless of proximity to the interface, inhibit binding with BRCA1. We will pair binding data with the secondary structure analysis and thermal stability of these variants (using circular dichroism) to better connect variant structure with PALB2 dysfunction. 

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and chronic neuroinflammation. Inflammatory signaling pathways such as nuclear factor-κB (NF-κB) play a critical role in the progression of neurodegeneration by regulating the expression of pro-inflammatory cytokines such as TNF-α and IL-1β. Targeting NF-κB signaling therefore represents a promising therapeutic strategy for reducing inflammation associated with AD. This study evaluated the effects of several novel anti-inflammatory compounds provided by P2D Biosciences and Dr. Geen’s research lab on TNF-α–induced NF-κB activation. HEK293 cells were transfected with an NF-κB responsive PRDII luciferase reporter and a CMV luciferase control, followed by treatment with novel compounds and stimulation with TNF-α. Luciferase activity was measured to quantify the effect of our molecules on TNF-a-induced NF-κB transcriptional activation. Results demonstrated dose-dependent reductions in NF-κB activation for several compounds, suggesting potential anti-inflammatory activity. These findings contribute to ongoing efforts to identify novel small molecules capable of modulating NF-κB signaling and may support future therapeutic development targeting neuroinflammation in Alzheimer’s disease.