Validating a New In Vivo Model to Study ALS

Author

Izabela J. Cimachowska, CUNY Bernard M Baruch CollegeFollow

Date of Award

Spring 5-1-2023

Document Type

Thesis

Degree Name

B.A. with honors

Honors Designation

yes

Program of Study

Biology

Language

English

First Advisor

Pablo Peixoto

Second Advisor

Krista Dobi

Third Advisor

Orrette Wauchope

Abstract

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed that emission of mitochondrial ROS can be specifically controlled in vitro by expression of a photosensitizing protein called mitokiller red. To study this in vivo, we generated the first animal model to express the chromophore mitokiller red in motor neuron mitochondria. We expect that photoactivation of the mitokiller protein in motor neuron mitochondria, will impair motor function and survival of Drosophila. Our results show that photoactivation of mitokiller in motor neuron mitochondria has slight negative effects on flipping abilities of third instar larvae in “with breaks” (WB) and “no breaks” (NB) conditions as well as survival rates in “no breaks” conditions. However, it has no effect on climbing abilities and mitochondrial function in either condition, as well as survival in the WB conditions.

Recommended Citation

Cimachowska, Izabela J., "Validating a New In Vivo Model to Study ALS" (2023). CUNY Academic Works.
https://academicworks.cuny.edu/bb_etds/170