Amyotrophic Lateral Sclerosis Disease Progression
By: Kayla Roh and Tarun Chethan
School: Fairmont Preparatory Academy and Greenwood High International IB
Summary
This project investigates the genetic and molecular mechanisms contributing to Amyotrophic Lateral Sclerosis (ALS). ALS, a fatal neurodegenerative disorder, leads to the degeneration of motor neurons, resulting in muscle weakness, loss of motor control, and eventual respiratory failure. The study focuses on the interactions between the SOD1 gene and proteins CCS (Copper Chaperone for Superoxide Dismutase) and SOD2 (Superoxide Dismutase 2), which play crucial roles in protein folding, oxidative stress regulation, and mitochondrial function. Mutations in the SOD1 gene lead to protein misfolding, aggregation, and toxicity, disrupting cellular processes. CCS delivers copper ions to SOD1, aiding its maturation, while SOD2 mitigates oxidative damage in mitochondria. Mutations in CCS hinder copper binding, increasing SOD1 aggregation and cytoplasmic toxicity. The research highlights the limitations of current therapies, including Tofersen, an FDA-approved gene therapy targeting SOD1. While Tofersen reduces neurodegeneration markers, it only slows disease progression rather than offering a cure. Future research directions include exploring CRISPR/Cas9-mediated gene therapies for personalized treatment and focusing on the overlooked role of SOD2 in ALS pathology. Advancing understanding of these protein interactions could lead to more effective therapeutic interventions and improved outcomes for ALS patients.
C9orf72 gene is located in chromosome 9
(Figure representation created by the authors:Kayla Roh and Tarun Chethan)
Video Presentation
Impact Statement
Tarun Chethan: Our project unravelled CCS and SOD2 Interactions with the systems of ALS progression. Discovering connections between SOD1 protein aggregation and how mutations in these genes can indirectly cause or increase the progression of ALS is explored in this project. I learnt various diverse topic of molecular biology and genetics throughout this course. Understanding the fundamentals between genes and their respective proteins and exploring the cross behaviour and linkage between various proteins was a very interesting experience. Understanding how research can be conducted outside a lab using the various resources and libraries available online furthered my knowledge in this field and has better prepared me to approach research in my further years.
Impact Statement
Kayla Roh: The project that Tarun and I completed with Elio was about how certain specific protein interactions affect the disease progression of Amyotrophic Lateral Sclerosis (ALS). Throughout this program, we were very well instructed on how to conduct research and extract knowledge on every available topic under the three fields of study using a variety of tools, such as DAVID analysis, String, and Uniprot. The mentors were always there to answer any of our questions, and I am very grateful to them, as well as the rest of the Elio team, for such an informative and fascinating program. Thank you for helping all of our ideas become reality.
Report White Paper
By: Kayla Roh and Tarun Chethan. The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of Elio Academy.
