Anne M. Brown receives NSF CAREER award to use computational modeling to study amyloid interactions
Millions of people worldwide have incurable Alzheimer’s, Parkinson’s and other diseases caused by fibrous deposits called amyloids. Amyloids attach themselves to organs such as the brain, liver, lungs, or heart or spread throughout the body, which can lead to these diseases, generally called amyloidosis. Treatments for these diseases include targeted therapies, chemotherapy, and even organ transplants.
However, much is unknown about amyloids on the molecular level.
Anne Brown, University Libraries’ assistant professor, science informatics consultant and health analytics coordinator, and affiliate of the Department of Biochemistry, received a five-year, $800,000 National Science Foundation Faculty Early Career Development (CAREER) award to use her molecular dynamics simulation expertise to shed more light on the differences between amyloids that harm and those that don’t.
“Amyloids serve a variety of roles in physiology and can be both functional and cytotoxic. Many are involved in signaling - helping control responses to hunger and pain, as an example” said Brown. “Amyloids are also naturally occurring in bacteria, forming biofilm networks that materials scientists are using as the basis for new sustainable materials.”
However, the same amyloid proteins that regulate hunger cues can mutate, misfold, and disrupt cell functioning. Brown will use computational modeling and high-performance computing resources to investigate the mechanisms of amyloid folding in the presence of membranes.
Kelsie King, a docotoral student in genetics, bioinformatics, and computational biology, has recently been the first author on three publications on this topic and is the lead graduate student for Brown's project.
“The membranes in various tissues are different. We would like to see how the membrane environment, or microenvironment, affects the shapes of amyloid aggregates. These microenvironments could dictate function and mechanisms involved in amyloidosis,” said Brown. “Eventually this could be used as a starting point for researchers looking to target and prevent these interactions.”
Brown is interested in this area of amyloid research for many reasons.
“I am interested in amyloids on multiple levels - the challenge they present in understanding fundamental protein biochemistry, the similarities and differences of functionality and utility across amyloids, and then the multidisease health connection. Alzheimer’s, especially, is something I’ve studied at a clinical level and at the atomistic level,” said Brown. “That is why I started with amyloid beta. Studying a concept from atom to person opens your perspective, allowing you to consider solutions that can impact multiple aspects of disease progression.
The CAREER award is the National Science Foundation’s most prestigious award for early career faculty, encouraging them to serve as academic role models in research and education and to lead advances in the mission of their organization. To satisfy the award’s requirements, CAREER recipients must find ways to integrate education and research into their projects, as well as conduct outreach.
Brown is excited about this award because it will help her create a different way to study these confounding protein byproducts through atomistic simulations rather than traditionally difficult microscopic wet lab experiments. Then, she will share her processes as a platform for enhancing STEM education. Her work will elevate undergraduate research programs, assist in the development of interdisciplinary training modules, and expand the program Experience in Molecular Modeling and Informatics that she created at Virginia Tech.
“At the conclusion of this five-year project, I will create substantial content and student training programs, assess them, and make them openly available for students and faculty across the world,” said Brown. “This project will provide an essential foundation for the advancement of biological knowledge related to amyloid proteins and simultaneously train and motivate future generations of scientists to use data and computation to expand their knowledge of biological phenomena.”