The Construction of Ataxin-1 Vectors for Analysis of Ataxin-1 Function in Development of Spinocerebellar Ataxia Type 1

Open Access
Author:
Wang, Timothy Moolen
Area of Honors:
Microbiology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Yingwei Mao, Thesis Supervisor
  • Sarah Ellen Ades, Honors Advisor
  • David Scott Gilmour, Thesis Supervisor
Keywords:
  • microbiology
  • vector
  • SCA1
  • ataxia
  • ataxin-1
Abstract:
Ataxias are a group of disorders that are characterized by a progressive loss of body movement control that can eventually be fatal. Symptoms result from a degradation of neural cells throughout the central nervous system which can be caused from a wide array of clinical causes including multiple sclerosis, alcoholism, or brain tumors. Additionally, ataxias may be caused by a genetic mutation, and these types of ataxias can be inherited through generations. Inherited ataxias may be autosomal recessive or dominant. One of the most prominent autosomal dominant forms of ataxia is spinocerebellar ataxia, or SCA. While there are many causes of SCAs, the most common mutation leading to the development of SCA is an elongation of CAG triplet repeat sequence. The CAG triplet encodes glutamine (Q) and the mutation leads to a long polyQ segment in the resulting protein. This mutant protein is prone to aggregation and causes neurodegeneration through an unclear mechanism. Recently scientists have been investigating the normal functions and protein interactions of ataxin-1, the protein responsible for development of SCA1. The Mao lab in which I performed my honors research is also interested in investigating the protein interactions of ataxin-1 in order to better understand the mechanism for SCA1 pathogenesis. In order to perform further studies, I was tasked with creating six different ataxin-1 vectors. Three vectors were for the wild type 30Q ataxin-1 and three vectors were for the mutant 80Q ataxin-1. Each of the three vectors had a different tag for further protein purification and identification. Future considerations for experimentation with the vectors I created are provided, along with an analysis of some of the most recent scientific research into ataxin-1.