Our mission is to effectively make use of the burst of DNA sequence information available in the 21^st century to interpret evolutionary mechanisms and health predictions.  

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Research Areas

Please contact me (dan.bolon@umassmed.edu) to find out about the details of current rotation projects. Most rotation projects will be focused parts of larger and ongoing efforts that are compatible with short rotations using existing mutational scanning tools and bioinformatic programs, including:

1. Investigating connections between HIV protease function and viral infectivity.
2. Analyze drug resistance in SARS-CoV2 Mpro, or the oncogene BCR-ABL1.
3. Investigate the mechanism of critical regulatory proteins in yeast including Hsp90 and Gsp1.
4. Use ancestral protein reconstruction combined with mutational scanning to understand the historical evolution of Hsp90.

Please check out our lab culture page for a description of expectations for lab members.  

Commonly-Used Techniques

  To address the critical knowledge gap between sequence and function, we pioneered the first technology using deep sequencing to systematically determine how every point mutation in a protein impacts its function. The EMPIRIC (Exceedingly Meticulous and Parallel Investigation of Randomized Individual Codons) and other related deep mutational scanning approaches provide rich datasets to improve sequence-function predictions and valuable empirical health and fitness information for critical genes. We utilize EMPIRIC sequence-function maps to investigate the structural and biophysical underpinnings of protein function as well as mechanisms that occurred during evolution over the past billion years and the rapid evolution of drug resistance that is a current threat to our health. The key technological advance that drives the EMPIRIC approach is the rapid generation of systematic libraries of specific mutations and the rapid assessment of the abundance of thousands of variants using deep sequencing. We continue to develop enabling and innovative technology to investigate critical questions in protein function and evolution