Grant: Doctoral Research Award: Canada Graduate Scholarships

Proteins are vital biological machines that ensure the survival of a cell. They participate in almost all crucial cellular functions, such as energy production, damage detection, and the facilitation of critical biological responses. The DNA that codes for these molecular machines, however, can often be mutated. Proteins can become malformed and toxic because of such mutations. This can be seen in neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease, and genetic diseases such as cystic fibrosis. There are many other rare genetic diseases that are characterized by a protein unable to reach its native form. The cell has a system to target and recycle error-prone proteins to prevent them from accumulating. To ensure that the problematic proteins are the ones being targeted, enzymes known as E3 ligases recognize them. Following recognition, E3 ligases tag these misfolded proteins with a unique molecule known as ubiquitin. Ubiquitin can be used to decorate proteins in various ways, allowing them to be marked for destruction or quarantine. This molecular signal has previously been linked to familial Parkinson's disease and various other degenerative diseases. Understanding how ubiquitin marks faulty proteins and how to regulate this process will lead to discovering new therapeutic targets in rare genetic disorders. This project aims to figure out which E3 ligases and related proteins are essential in eliminating errant proteins, how they triage damaged proteins, and how this information may be used to develop new treatments for rare disorders.