About This Project
Alzheimer's Disease, the 6th leading cause of US deaths, is characterized by amyloid-beta(Aβ) plaques and trace metal level imbalances. How this interaction occurs on the molecular level is currently unknown. Protein HSP-16.2 is known to interact individually with Cu,Zn,and Aβ, but their combined interaction has not yet been researched. I hypothesize that HSP-16.2 is involved in the binding of Aβ to Cu and Zn and increases in the levels of one trace metal cause increases in Aβ and other metals.
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What is the context of this research?
Trace metal level imbalances are known to naturally occur in a majority of the aging population, especially in Alzheimer's Disease (AD) patients. Aβ plaques, which characterize AD, are known to bind to Cu and Zn with high affinity. Current research does not address the molecular pathways that characterize this Cu-Zn-Aβ interaction and whether an increase in one trace metal directly causes an increase in other trace metals and Aβ. This research plans to address these knowledge gaps by using C. elegans, a transparent nematode whose neural pathways have been fully established, as a model. HSP-16.2 is a protein known to interact with Cu, Zn, and Aβ individually. By examining its role in the combined Cu-Zn-Aβ interaction, a Cu-Zn-Aβ interaction pathway will potentially be suggested.
What is the significance of this project?
Alzheimer’s Disease is the 6th leading cause of US death, with 1 in 10 people age 65 or older having AD! Since there is currently no cure, better understanding AD pathogenesis is crucial as the size of the elderly population continues to grow. Most publications that explore the relationship between trace metals and Aβ have found that increases in Cu and Zn individually cause increases in Aβ. There are, however, some contradictory reports. The molecular mechanisms driving this causal relationship are not well understood. Finally, whether an increase in one trace metal is the cause of increases in other trace metals in addition to Aβ has not been well explored. Better understanding how Cu, Zn, and Aβ interact will help develop a cure that targets the correct molecular pathways.
What are the goals of the project?
The research goal is to test the relationship of Cu and Zn on Aβ and how they interact.
Phase 1: C. elegans, a model for Alzheimer's Disease, will be supplemented with trace metals Cu and Zn individually to demonstrate whether an increase in one trace metal causes an increase in other trace metals and Aβ aggregation development. Aβ will be measured using Congo Red dye and Cu and Zn will be measured using assays.
Phase 2: The expression level of protein HSP-16.2, which is known to individually interact with Cu, Zn, and Aβ, will be measured over the lifespan of an amyloid-beta producing C. elegans strain that mimics AD progression to suggest potential molecular interaction pathways through which Cu, Zn, and Aβ interact. HSP-16.2 expression will be measured via fluorescent illumination.
-4 C. elegan strains: a wildtype female, wildtype male, amyloid-beta aggregation producing strain, and Hsp-16.2::GFP strain. C. elegans will be used as model organisms to study the effects of trace metals on the progression of Alzheimer's Disease.
-Stereo Microscope Fluorescence Adapter: adds fluorescence to a microscope to allow the quantification of Hsp-16.2::GFP fluorescence.
-Centrifuge: used to lyse C. elegans
-L15 buffer: used to lyse C. elegans
-CuCl2 and ZnSO4 powders: will be added to the C. elegans' diet to determine the effect of an increase in trace metal levels on the progression of AD. This mimics the natural increases in trace metals that accompany human aging.
-Zn and Cu Colorimetric Assays: quantify the level of Cu and Zn in C. elegans after Cu and Zn are added to the diet. This quantification will allow conclusions to be made about the uptake of Cu and Zn when amyloid-beta plaques are present.
Once funding is secured in about 1 month, Phase 1: determine the correlation between Cu, Zn, Aβ by measuring Aβ, Cu, and Zn levels over C. elegans' lifetime as Cu and Zn are added to the diet. Phase 2: determine why the Cu, Zn, Aβ correlation exists by measuring HSP-16.2 expression and Aβ, Cu, and Zn levels without any supplementation. C. elegans' average lifetime is 2-3 wks. There will be 2 trials/phase. Therefore, each phase should last 1-1.5 months. Then a publication will be written.
Nov 30, 2020
Start Running Phase 1 Trials
Dec 04, 2020
Jan 04, 2021
Start Running Phase 2 Trials
Feb 01, 2021
Analyze Data Collected and Observe Trends
Feb 08, 2021
Begin Writing Research Paper
Meet the Team
I'm a junior at Princeton HS and in my 2nd year of the research program. I have always had a strong passion for neuroscience and love to ask many questions about why phenomena occur. Through reading papers about current knowledge of Alzheimer's Disease (AD), it is clear how many unknowns persist in the field and this has sparked a passion within me to help better understand the molecular interactions characterizing AD and other neuroscience diseases. A few years ago, after suffering a concussion while playing basketball, I developed a prototype for a ball that could prevent concussions by deflating prior to impact. I have written neuroscience-related essays such as The Developmental Lags of the Juvenile Brain and Its Impact on Incarceration. Upon submission to the Scholastic Writing Awards, I won several NJ Gold Awards and one national Silver Award which only the top 1% of writers in the nation receive. Additionally, I am currently vice president of my school's neuroscience club and have helped to greatly expand the club. Upon my initiative, the club organized numerous summer workshops to introduce young scientists to the fascinating world of neuroscience. This summer I also volunteered at the Children's Fund Science Program to teach underprivileged children several science related concepts and how to think like a science researcher. I love teaching younger students who are passionate about science and look forward to continuing. Due to my passion for science and math, I was named my middle school's top grade-wide scientist two years and top mathematician one year. I balance my academic passion equally with my passion for track. I am captain of the team as well as a long jumper and hurdler. I believe that sports are crucial to the mental and physical wellbeing of students. Overall, I am very excited about conducting AD research and hope to receive funding soon!
- $2,250Total Donations
- $102.27Average Donation