BRCA1 plays an important role in the DNA damage response pathway by promoting the facilitation of homologous recombination with its binding partner, PALB2. Inherited loss of function BRCA1 variants disrupt this highly conserved and stabilized protein-protein interaction, preventing the complex from repairing double stranded breaks in DNA. Hereditary breast cancers have been treated using well-established methods, such as PARP inhibitors and DNA damaging agents. However, nonhereditary breast cancers that retain BRCA1 function are not susceptible to these treatments because they are able to effectively repair their DNA, leading to a proliferation of the cancer cells.
Here, we investigate whether small peptide-mimicking molecules, such as stapled peptides and macrocycles, have the ability to disrupt the BRCA1 and PALB2 interactions. We designed a short sequence of amino acids that mimicked BRCA1’s coiled coil region, the area that binds to PALB2. This sequence was then “stapled” with a short hydrocarbon to create a stapled peptide. The macrocycles were designed by targeting amino acids necessary to the BRCA1/PALB2 interaction. Binding interactions between the peptide mimics and PALB2 were measured using isothermal titration calorimetry (ITC). This method is incredibly reliable for sensing the heat changes upon binding to predict protein interactions. Our results suggest that macrocycles do not inhibit the BRCA1/PALB2 interaction, while the stapled peptides may be competing with BRCA1 for the binding site of PALB2.
Our findings indicate that due to the high specificity and conservation of the BRCA1/PALB2 interaction, finding a molecule to completely disrupt this interaction would require high throughput screening methods to test multiple compounds at once. These proteins may not be susceptible to rational drug design, so testing a variety of compounds may be the best way to disrupt this interaction. Further refinement of the peptide length, sequence, staple placement, and staple chemistry, as well as different macrocycles, may also be useful to effectively inhibit this interaction. Targeting the BRCA1-PALB2 interaction remains a promising strategy for treatment of non-hereditary breast cancers.

Developing Effective Husbandry Protocols for Larinoides
Reliable laboratory husbandry is essential for maintaining healthy spider populations used in ecological, physiological, and behavioral research. However, standardized protocols remain limited, particularly in spiderlings. This project focused on developing and refining husbandry techniques to optimize spider survival, health, and rearing of young under lab conditions. This study establishes and evaluates husbandry protocols for Larinoides orb weavers (Family Araneidae), a group of riparian spiders known for constructing vertical orb webs and their ecological role as important predators in aquatic-terrestrial food webs. Six adult spiders were collected from the Trinity river in Fort Worth, TX and mated in the laboratory. Their spider hatchlings were maintained in individually prepared vials containing artificial vegetation designed to support web attachment and movement. Feeding regiments using immobilized fruit flies and hydration strategies using a diluted honey solution were implemented. Observations of survival, activity, and general health were recorded. The husbandry system promoted consistent housing and care routines to promote spider survival in a laboratory setting. The methods used provided a reproducible system that consistently allowed spiders to successfully mate, reproduce, and nurse spiders to adulthood. These findings will contribute to the rapidly expanding field of spider husbandry by providing a reproducible husbandry system.

BRCA1, a tumor suppressor protein, when dysregulated, leads to a significant proportion of hereditary breast and ovarian cancers. Better understanding the specific enzymatic functions of BRCA1 and the downstream phenotypic effects is important for advancing cancer research. Because crucial signaling pathways controlled by BRCA1, including nucleosome ubiquitylation, are similarly conserved between humans and Caenohabditis elegans (C.elegans), this organism is a valid model to determine the phenotypic effects of BRC-1, a homolog of BRCA1, when its molecular signaling pathways are altered.
It was previously discovered that wild-type N2 C.elegans, which retains a fully functional BRC-1 protein, mainly display an XX genotype and hermaphrodite phenotype. Conversely, the xoe4 knockout mutant has an absent BRC-1 protein and displays an increased frequency of XO males, presumably due to loss of BRC-1 function in proper meiotic crossover during gamete formation. Yet, it is unknown whether the nucleosome ubiquitylation signaling pathway of BRC-1 directly contributes to successful meiotic crossover and XX hermaphrodites.
We hypothesize that the syb5376 mutant strain, which contains the BRC-1 protein but lacks facilitation of nucleosome ubiquitylation, would exhibit an intermediate phenotype with a male frequency higher than the N2 wild-type strain but lower than the xoe4 knockout strain. To test this hypothesis, we quantified the ratio of male to hermaphrodite progeny and compared male frequencies across all three strains.
Consistent with our hypothesis, the syb mutant illustrated a male frequency that was in between the N2 wild-type and xoe4 knockout strains. This suggests that nucleosome ubiquitylation of BRC-1 mediates successful meiotic crossover, but also contributes to this function either by mediating other protein-protein interactions or ubiquitylation of an alternate substrate.
Ultimately, these findings detail the importance of nucleosome ubiquitylation of BRC-1 in C. elegans, which is useful for determining the importance of nucleosome ubiquitylation of BRCA1 in humans. More broadly, this work advances our understanding of how specific molecular functions of BRCA1 contribute to genomic stability and increase breast and ovarian cancer susceptibility.

The Dreissena polymorpha (zebra mussels) and Dreissena bugensis (quagga mussels) are invasive, freshwater species native to Eastern Europe. Since their introduction to the Great Lakes region of the United States in the 1980s, both dreissenid mussels have quickly expanded throughout inland waterways and caused significant economic impacts and ecological changes. Both zebra and quagga mussels have greatly exceeded the expansion range of predicted models, spreading throughout North America and south into warmer waters including Texas. The mechanism facilitating this expansion is a topic of great interest. Understanding differences between cold-water and warm-water adapted mussels may help us to better predict their spread into Texas. In my project, I investigated the differences in temperature tolerance by analyzing survival rates of adult mussels in varying degrees of water. Furthermore, I analyze differences in spawning of egg and sperm and resultant fertilization success between the two groups. Together, these findings provide insight into the temperature-related survival and reproductive strategies that may enable these mussels to continue expanding beyond their predicted range into warmer freshwater environments.

Zebra mussels are an invasive species known to cause adverse ecological impacts by outcompeting native species, disrupting the food web, and destruction to aquatic habitats. Zebra mussels often aggregate on hard surfaces, clogging pipes, damaging boats and infrastructure, etc., leading to costly economic challenges. As broadcast spawners, they release eggs and sperm into the water column where fertilization and larval development occurs. During this process, the larvae may travel long distances enabling their spread into new locations, including Texas. These early stages of the lifecycle (gametes, larvae) zebra mussels will be most sensitive to external factors and conditions. They may also be the most sensitive to control mechanisms such as copper or bleach treatments. Little is known about exactly how long gametes remain in the water prior to fertilization and how long after spawning are they viable. The objective of this research project is to gain a deeper understanding of Zebra mussel reproduction with a focus on gamete viability. I will assess sperm viability using multiple assays including established procedures such as sperm motility using video analysis, gamete and sperm longevity. We have developed novel a fixed egg assay that allows analysis of sperm binding to eggs without the need for freshly spawned eggs. These assays will allow us to determine how long zebra mussel sperm and eggs are viable after release.