Research

Our lab focuses on developing and applying Physical Bioinformatic techniques to measure rates of translation transcriptome-wide and their molecular origins as relates to fundamental biology and disease.

Research Methods

We employ a combination of:

• High-throughput sequencing
• Computational analysis
• Physical modeling
• Bioinformatics approaches

Core Research Areas

Co-translational Protein Folding

We investigate how proteins begin folding while they are still being synthesized by the ribosome. Our research has revealed that the rate at which individual amino acids are incorporated during translation can dramatically affect protein folding outcomes, potentially leading to misfolding and disease.

Translation Elongation Kinetics

Using advanced computational methods and ribosome profiling data, we study how translation speed varies along mRNA sequences and how this affects protein behavior. Our lab has developed innovative tools like RiboA for accurate analysis of ribosome profiling data.

Mechanochemistry in Translation

We explore how mechanical forces generated during protein synthesis can feed back to influence translation rates. Our work has uncovered how charged amino acid sequences can create forces that alter the ribosome’s catalytic cycle.

Protein Misfolding and Disease

We investigate novel mechanisms of protein misfolding, including non-covalent lasso entanglements, and explore therapeutic strategies to prevent misfolding-related diseases. Our recent work has shown how small molecules might be designed to prevent specific types of misfolding.

Computational Method Development

We develop theoretical frameworks and computational tools to predict and understand co-translational processes. Our approaches include:

• Markov chain models for co-translational folding
• Integer programming methods for ribosome profiling analysis
• Molecular dynamics simulations of protein synthesis
• Structure-based models for protein folding

Research Impact

Our research has implications for:

• Understanding protein folding diseases like Alzheimer’s, Parkinson’s, and prion diseases
• Developing new therapeutic strategies for misfolding-related conditions
• Advancing biotechnology through improved protein production methods
• Enhancing our fundamental understanding of how proteins achieve their functional states

Collaborative Approach

We collaborate with experimental groups worldwide, combining computational predictions with experimental validation to advance our understanding of protein synthesis and folding. Our work spans from fundamental biophysics to practical applications in medicine and biotechnology.