I’m Sorry We Don’t Have a Catwalk (Animal Models)
Title by Ava Masse
During a time when heightened attention is being paid to the value of health, the Tufts community takes pride in knowing so many of our students are involved in cutting-edge, relevant biological research. These posters cover a lot of different crucial medical issues: ones that can help us better understand kidney disease and severe cardiovascular disease, the importance of improving WASH infrastructure and hygiene behavior, and research with tadpoles that helps us better understand tissue engineering and computational biology.
Jay-Miguel Fonticella’s Project is entitled, “The Characterization of Remodeling and Non-Remodeling Craniofacial Defects in Pre-Metamorphic Xenopus laevis tadpoles.” His research looks at how the regulatory networks coordinating cell proliferation, migration, and differentiation in craniofacial (CF) development are highly conserved between vertebrate species. The level of intricacy in the processes involved in the formation of CF structures results in an elevated likelihood of creating CF defects. In this study, his team examined the ability of pre-metamorphic Xenopus laevis (African clawed-toed frog) tadpoles to correct CF defects through physiological tissue remodeling, a process defined as the renovation of existing tissues. Because the underlying processes that mediate the remodeling of head structures have not been well-studied, characterizing the self-correction of malformed structures is the focus of their current research. They investigated a possible role for eye tissue during CF remodeling in our system. To test this hypothesis, we exposed X. laevis embryos to Thioridazine, resulting in eye disfigurations, and Ivermectin, resulting in primarily ventral defects. We found an interesting correlation between the presence of eye-defects and the ability to remodel malformed structures. Since the eyes have been postulated to act as a potential organizer in early CF development, our findings suggest a possible link between the organizational role of eyes in later stages of CF development.
Rachel Xiang’s project is entitled, “Using in Silico Methods to Examine Atherosclerosis in Preclinical Mouse Models.” Her research focuses on atherosclerosis, which is a chronic inflammatory disease where lipid-rich plaques form in blood vessels. Atherosclerosis is a potent risk factor for more severe cardiovascular disease (CVD), such as heart attack and stroke. As CVD remains the leading cause of death worldwide, there is a critical need to study the mechanism by which atherosclerosis develops. Animal models are extensively used to investigate molecular mechanisms of human disease, and the ApoE KO and LDLR KO mouse models are two widely used preclinical models of atherosclerosis. Her team hypothesized that a systematic analysis of integrated preclinical data may identify novel signaling pathways and regulatory networks of atherosclerosis in mouse models. Data were extracted from 716 ApoE KO and 422 LDLR KO manuscripts published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology. Extracted data described the impact of an experimental gene perturbation on atherosclerotic plaque size and/or composition. Impacts on plaque size, inflammation, and lipid content were analyzed using Ingenuity Pathway Analysis software, first separately within each model and then as an aggregate dataset.Integration of these data identified distinct genetic programs in each model system, as well as similarities between the two.
Daanya Salmanullah’s project is entitled “CRISPR/Cas9 Zebrafish Models Do Not Recapitulate Four Human Monogenic Causes of Renal Cystic Kidney Disease.” Nephronophthisis is a recessive cystic kidney disease that is defined by its effects on the kidney, retina, liver, and brain early in life. This condition is characterized as a ciliopathy because of the way a suite of mutations localized at the cilia-centrosome in kidney cells cause the disease. Two mutations in the genes cep164 and sdccag8 were found to contribute to the presence of this condition in patients using Whole Exome Sequencing. In order to create an animal model for Nephronophthisis, CRISPR/Cas9 — a genome editing technology — was used to generate transgenic zebrafish lines, one for each of the two genes. Because of the genomic similarities between zebrafish and humans, zebrafish have analogous kidney structure and function to that of humans, which makes them a good model organism for human kidney diseases. Using multi-generational breeding between the two transgenic fish lines, double knock-out zebrafish (fish with mutations in both the cep164 and sdccag8 genes) were generated. By analyzing the survival of these fish through survival curves, the disease onset and pathogenesis of nephronophthisis could be tracked. Overall, the results showed that the mutations in cep164 and sdccag8 did not reproduce the features of this ciliopathy in zebrafish.
Cara Hernandez; Catherine Gross, and Sarah Claire Loeb’s project was entitled “Moving Beyond MDA to Control STH Infections through WASH, Hygiene Education, and Community Engagement.” Over 1.5 billion people worldwide are afflicted by soil-transmitted helminth (STH) infections: Ascaris lumbricoides, hookworm, and Trichuris trichiura (Ercumen et al., 2019). The disease burden falls mainly on low and middle-income countries (LMICs) without adequate water, sanitation, and hygiene (WASH), since transmission mainly occurs through soil contaminated with infected feces (Khan et al., 2019). Infection control has typically relied on annual school-based mass drug administration (MDA), however, MDA is not a long-term solution because it does not interrupt environmental transmission (Khan et al., 2019; Vaz Nery et al., 2019, Ziegelbauer et al., 2012).WASH infrastructure and hygiene behavior must be improved to reduce environmental transmission of STH infections (Ecrumen et al., 2019). WASH efforts include access to safely managed water sources and latrines and adequate fecal management (Worrell et al., 2016). However, WASH infrastructure improvements must be accepted by the community and coupled with behavior change to achieve full benefits (Al-Delaimy et al., 2014; Parker et al., 2008; Watson et al., 2017). Community engagement centers communities in the design, implementation, and evaluation of interventions to increase their acceptability and maximize sustainability (Clarke et al., 2018; Muluneh et al., 2020), thus improving the ability of MDA and WASH interventions to achieve long-term and sustainable reductions in STH infections (Clark et al., 2018; Gyorkos et al., 2013; Muluneh et al., 2020). The objective of their review is to examine the impact, methods, and takeaways from interventions that supplement MDA on efforts to control STH infections globally and demonstrates how community engagement practices can augment the effectiveness of interventions.
