Using Drosophila melanogaster as an Integrated Model to Elucidate the Cellular and Genetic Mechanisms Underlying Traumatic Brain Injury (TBI)

Overview

Thomas Jefferson High School for Science and Technology Background: Traumatic brain injury (TBI) is a leading international cause of morbidity and mortality and its outcome is significantly influenced by poorly understood cellular and molecular responses to the initial impact. This project’s objectives were: 1) To assess apoptosis levels in brains of Drosophila subjected to TBI, 2) To define the immune system’s response to brain injury, and 3) To detect intestinal barrier dysfunction in Drosophila following TBI. Methods: A “high-impact trauma” (HIT) device was used to inflict brain injury. An antibody to cleaved-Caspase-3 was used as an apoptotic marker in whole Drosophila brains. Immune response was assessed by quantifying Anti-Microbial Peptides (AMP) gene expression, using qRT-PCR. Intestinal barrier dysfunction was detected by the presence of a non-absorbable blue food dye outside of the digestive tract after feeding. Resu lts: Increased apoptosis was detected in Drosophila brains subjected to TBI, by measuring cleaved caspase. This was especially evident in the mushroom bodies known to play a role in olfactory learning and memory. TBI flies showed an enhanced innate immune response as measured by increased gene expression of the anti- microbial peptide, Diptericin B. More flies with TBI had the “Smurf” phenotype, compared with controls, demonstrating that impaired gut permeability is a non-neuronal effect of severe TBI. Conclusion: TBI causes distinct biochemical and physiological alterations. An improved understanding of these secondary sub -cellular mechanisms of TBI is a vital prerequisite for developing effective interventions. Engineering a DNA Aptamer Nanomachine Platform for T Cell Detection Based on Cancer Metabolites Jared Lenn Bronx High School of Science Bronx, New York Supervising Scientist: Dr. Lina Freage CUNY Lehman College Aptamers, oligonucleotides evolved to be specific against a target ligand, are promising as selective drug delivery agents for cancer cells that express unique biomarkers on their surfaces. However, cell surface antigens do not always differentiate among cells as specifically as desired. The altered metabolism of cancer cells results in pronounced changes to their microenvironment, particularly through altered metabolite concentrations. In this study these metabolite markers of tumor cells are leveraged to rationally engineer a two-stage aptamer nanomachine, in which activates the aptamer cell binding domain is activated only once its metabolite domain has been bound. This nanomachine recognizes ATP as its metabolite, and binds to T Cells when activated. For this reason, I termed the aptamer ART, for ATP-Regulated T1C. We demonstrate that aptamer binding activity is controllable by the conformational status of an intramolecular domain via helix destabilization. Furthermore, it is shown that cancer indicative metabolites can be used to regulate binding of this nanomachine to cancerous T Leukocytes. In this way, we have developed a new platform for specific cancer recognition and drug delivery, which relies not only on cell-specific antigens but also on the conditions surrounding the cells. This technology will enable higher dosages of chemotherapeutic agents to be used with reduced side effects to healthy cells, enabling a safer and more effective form of chemotherapy

Awards (1)

• 2nd Place Medicine & Health/Behavioral Sciences

Competition history

• JSHS 2020 Category not listed

Resources

• National JSHS abstract book ↗

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