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α-sheet in Amyloid Diseases

We propose that α-sheet plays a critical role in both the aggregation and toxicity of soluble oligomers.

Bacterial Amyloid in Biofilms

We design α-sheet peptide inhibitors that target pre-amyloid oligomers in three pathological biofilms – S. aureus, P. aeruginosa, and E. coli – to combat healthcare associated infections (HAI).

Characterizing the α-sheet Structure

We perform atomistic simulations of amyloid proteins under amyloidogenic conditions to model the early conformational changes that occur during amyloidogenesis.

Amyloid Inhibitor Design

We design proteins and peptides with α-sheet structure to target toxic amyloidogenic intermediates and inhibit aggregation and disease progression.

Conformational Changes in Amyloidogenesis

We have observed the formation of α-sheet in simulations of multiple proteins, including transthyretin, superoxide dismutase, prion, and lysozyme.

Protein Folding-Unfolding Pathways

We have performed >6k protein simulations under both native and amyloidogenic conditions to elucidate common rules governing the structure and properties of all transition states and folding pathways.

Peptide and Protein Design

We use MD simulations to engineer protein variants that can provide insights into the biophysical properties of proteins or be formulated as diagnostic tools, therapeutic agents, or functional biomaterials.

Software Development

We develop software to build, analyze, and visualize protein structure and dynamics.

Welcome to the Daggett Research Group.

Our group is currently focused on protein unfolding and disease where we combine both computational and experimental approaches. We have developed a database to simulate representatives of all known protein folds, an effort we call Dynameomics, which has led to the largest collection of simulations and protein structures in the world.

We also pursue simulations of protein unfolding related to amyloidogenesis. We found that amyloidogenic peptides and proteins under amyloidogenic conditions changed structure and formed a novel, nonstandard secondary structure, which we dubbed α-sheet. We proposed that α-sheet structure is linked to toxicity during amyloidogenesis, and have developed an α-sheet library to test our peptide inhibitor designs in 1) mammalian amyloid disease systems, and 2) bacteria that use amyloid fibrils for biofilm stability to evade the host immune response and antibiotics. Our compounds inhibit aggregation and toxicity by binding the toxic oligomers that form en route to mature amyloid.

Valerie Daggett, Ph.D.

Principal Investigator

Professor, UW Bioengineering
Founder & CEO, AltPep Corp.

News

Dylan Shea Publishes in PNAS

April 2019 Dylan Shea, graduate student in Molecular Engineering in the Daggett Lab, is first author on a paper in PNAS demonstrating that the toxic...

Daggett Group Research in Medical News Today

April 2019 News regarding our research. Learn...

Daggett Group Research in Genetic Engineering & Biotechnology News

April 2019 More news regarding our research. Learn...

Dylan Shea Spurs Elon Musk to Commit to Clean Water for Flint, MI

July 2018 Dylan Shea, musician and molecular engineer of the Daggett Lab, spurred Elon Musk to state his commitment to supply houses in Flint,...

ilmm Almost Ready!

We are putting the final touches on documentation and licensing paperwork so that we can release our molecular modeling package in lucem molecular...

People

Anthony Heng Receives 2022 UW 50th Reunion Scholarship, Rex & Ruth Robinson Scholarship

Congratulations to Anthony Heng for receiving the 2022 UW 50th Reunion Student Assistance Fund Scholarship and 2022 Rex & Ruth Robinson...

Sarah Nick is a 2021-2022 ITHS TL1 Trainee

Congratulations to Sarah Nick for receiving the 2021-2022 Institute of Translational Health Sciences TL1 Training Grant! Sarah also received the UW...

Tatum Prosswimmer Receives CoE Dean’s Fellowship & MBTG

Congratulations to Tatum Prosswimmer for receiving the College of Engineering Dean’s Fellowship and the Molecular Biophysics Training...

Dylan Shea Spurs Elon Musk to Commit to Clean Water for Flint, MI

July 2018 Dylan Shea, musician and molecular engineer of the Daggett Lab, spurred Elon Musk to state his commitment to supply houses in Flint,...

Natasha Paranjapye is a 2018 Mary Gates Research Scholar

Congratulations to Natasha Paranjapye who received a Mary Gates Research Scholarship for 2018!