CBE Seminar (Zoom): Beyond Amyloid - Alzheimer’s Amyloid-β Oligomers, Designer Peptide Nanostructures and Peptide Analogs

Non-UCI people- please use this registration link: https://forms.gle/VXaBwZ7Kn3pvCNDB9

Abstract: My group specializes in using solid-state NMR spectroscopy to understand the detailed molecular structures of protein and peptide (small protein) aggregates. I will discuss our work on amyloid fibrils, smaller non-fibrillar aggregates and nanostructures formed by designer molecules.

Amyloid fibrils are β-sheet nanofibers. The association of amyloids with “protein aggregation diseases” (e.g., Alzheimer’s) motivated decades of effort in structural biology. Much has been learned about amyloid fibrils’ molecular structures, but we are aware of numerous protein aggregates with presently unknown structures. It is mysterious how different structures affect pathology. One class of poorly understood peptide aggregates is oligomers, assemblies of 50 or fewer peptide molecules. Oligomers have exhibited higher toxicity than fibrils in cell culture, animal models and studies on human samples. I will present a newly developed structural model of a 32-mer oligomeric aggregate of the Alzheimer’s amyloid-β peptide. I will discuss what this structure reveals about oligomer formation pathways and the relationship to pathology.

Structural biology of protein aggregation has also inspired a new discipline: the rational design of nanostructured peptide assemblies. Closely related is the design of peptoids, which mimic the sequence-defined nature of peptides but differ in atomic connectivity. I will present structural studies of β-sheet and α-helical designer peptide assembly, cooperative co-assembly of distinct but complementary peptides and assembly of peptoid nanosheets. Studies of designer systems have revealed previously unknown assembly mechanisms, such as post-assembly helix-to-sheet transformation and assembly-driven amide bond isomerization. These phenomena inspire new theories and interpretations related to naturally occurring pathological aggregation.

Bio: The Paravastu laboratory specializes in the application of solid-state NMR spectroscopy to detailed structural analysis of peptide, protein and peptide analog assemblies. Systems of interest include pathological aggregates, nanostructured materials created via designer peptide assembly, and assemblies of non-natural peptide-mimetic molecules.  The Paravastu laboratory’s research projects are unified by the use of nuclear spin physics and computer modeling to uniquely determine 3D arrangements of atoms. Recent efforts seek to integrate NMR experimental design with computational peptide design, so that computer-designed structures can be tested efficiently with minimal experiments.

Paravastu first became interested in molecular-level science and engineering as an undergraduate student at MIT (S.B., chemical engineering, 1998).  As a doctoral student (Ph.D., UC Berkeley, 2004), he developed a drive to integrate chemical engineering research with modern techniques in physics and physical chemistry.  He learned to apply NMR spectroscopy to structural biology as a postdoc at the Laboratory of Chemical Physics at the National Institutes of Health (2004-2007).  Paravastu started as an assistant professor in 2008 at Florida State University, where he worked with the National High Magnetic Field Laboratory.  He started his current position at Georgia Tech in 2015. 

Host: Assistant Professor Herdeline Ann Ardoña