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SC-INBRE at Winthrop

The Lammi Lab

Spectroscopic Investigations of Folding and Association in Alzheimer's Amyloid-β Peptide

 Lammi, Robin   Name:  Robin Lammi 
Title:  Associate Professor of Chemistry 
Postdoctoral Fellowship, Single-Molecule Spectroscopy, University of Texas-Austin
Ph.D., Inorganic Chemistry, Washington University
B.A., Chemistry, Luther College
Office:  313A Sims Science Building  
Phone:  803/323-4946 
Physical Inorganic and Biophysical/Bioinorganic Chemistry, Fluorescences Spectroscopy, Nanoscience
Our research is focused on studies of amyloid-β peptide (Aβ), the small protein whose mis-folding and association are implicated in Alzheimer's disease (AD). We use spectroscopic methods to study these processes in bulk solution and at the level of single proteins, which allows us to investigate Aβ monomers and a variety of the oligomers (which contain multiple associated peptides) linked to Alzheimer's symptoms. Students use a number of different spectroscopic techniques, including absorption, fluorescence, steady-state, time-resolved, and single-molecule methods, to address questions at the forefront of biophysics and Alzheimer's research.

SC-INBRE Research

Evaluating Small-Molecule Inhibitors of Amyloid-β Aggregation

Amyloid-β peptide is formed through the enzymatic cleavage of the amyloid precursor protein (APP). In its monomeric form, Aβ is not harmful to neurons, and may even be protective; however, a variety of factors promote the association of monomers into soluble oligomers and larger, insoluble, fibrils that are toxic to neurons. One approach to treating Alzheimer's disease is to inhibit and/or reverse Aβ aggregation. A wide variety of potential inhibitors have been investigated, including natural products, other peptides, and small organic molecules. We are collaborating with Dr. Jay Hanna's laboratory here at Winthrop to design, synthesize and evaluate potential small-molecule inhibitors. Thus far, Dr. Hanna and undergraduate Craig Stevens have prepared three aromatic polyphenols that Craig and I are now evaluating for inhibitory activity. We are employing the Congo Red spectral-shift assay, in which Congo Red dye binds specifically to amyloid oligomers with β-sheet structure. By following dye binding as a function of time, we are able to monitor the course of aggregation into β-structured oligomers. Our initial studies have been promising, allowing us to identify useful structural elements for the design of future inhibitors.

Probing Structures and Dynamics in Dimers of Amyloid-β Peptide

Over the last 10-15 years, researchers have gained new understanding of Alzheimer's disease. Although insoluble amyloid-β fibrils – the primary components of senile plaques found in AD brain – were long thought to be the pathogens, recent evidence shows that the build-up in the brain of very small Aβ oligomers, including dimers, trimers and tetramers, is more closely linked to disease progression. Unfortunately, while fibril structure is fairly well studied, very little is known about the structures of these smallest oligomers, complicating efforts to combat them. In work funded by the National Science Foundation (RUI Grant CHE-0848824), we are using single-molecule fluorescence methods to examine structures and structural dynamics in Aβ dimers. In this way, we are able to study dimers, one by one, even in the presence of other small oligomers, and to fully appreciate the variety of structures and properties they exhibit. We are currently comparing and contrasting dimers in the presence and absence of bound zinc ions, which may play an important role in oligomer formation.

Current Group Members

Rebecca Mitchum (2009-Present), Craig Stevens (2010-Present), Emily Amenson (2011-Present), Iris Strzyzewski (2011-Present)

Craig is working with both Dr. Hanna and me to synthesize and evaluate small-molecule inhibitors of amyloid-β aggregation. Rebecca, Emily and Iris are investigating structures of amyloid-β dimers, both in the presence and absence of zinc.

Former Group Members

K. Michelle Wood (2004), Shakena Daniel (2004-2006), Joseph Goodwin (2005-2007), Kyle Dukes (2005-2008), Cynthia English (2006), Brent Girard (2007), Cassie Rodenberg (2007-2008), Carol Perkins (2008), Mattie Ingersoll (2009), Lyndsey Powell (2006-2010), Chelsea Russell (2008-2010), Abby Bradner (2009-2011)