Mechanisms of proteostasis network vulnerability in Kennedy’s Disease
Summary Description
Kennedy’s Disease is a rare disorder that causes muscle weakness by damaging nerve and muscle cells through the toxic buildup of proteins. This happens when the androgen receptor becomes faulty, causing proteins to misfold and clump together. Our cells have a built-in defense system – called the proteostasis network – that normally keeps proteins healthy by managing their production, folding, and removal. But this system does not work the same in every person or every tissue, and that difference can influence how badly someone is affected by disease. This project uses tiny worms, called C. elegans, to explore how natural differences in these protein-defense systems affect disease vulnerability. By closely tracking protein clumping and behavior in individual worms, we will identify who is more resilient and why. We will also study genetic differences and test ways to strengthen these defense systems using gene editing and drugs. In the long run, this research could help us find new ways to protect people from diseases like Kennedy’s disease by boosting their natural ability to manage harmful proteins.
Bio
Laura Bott earned her degree in biochemistry at Imperial College London (UK) and completed her Ph.D through the Graduate Partnership Program in Neuroscience at the Karolinska Institute (Sweden) and the National Institutes of Health (Bethesda, MD). Her doctoral research examined the interplay between the androgen receptor and cellular protein degradation systems in Kennedy’s disease, with the aim of accelerating mutant protein turnover for therapeutic benefit. This work laid the foundation for two clinical trials in patients with Kennedy’s disease, including the AJ201 trial.
Laura pursued her postdoctoral training at Northwestern University (Evanston, IL), where she studied the regulation of protein homeostasis (proteostasis) in aging and disease. During this time, she developed genetically encoded biosensors that enable real-time monitoring of proteostasis and discovered that proteostasis capacity varies substantially among individuals. Her current research focuses on uncovering the molecular basis of this interindividual variability and how these differences shape disease risk.
