Pioneering the next generation of diagnostic and therapeutic agents…
Students in the Chaput lab are working to develop the next generation of diagnostic and therapeutic agents based on novel synthetic genetic polymers that are capable of heredity and evolution. This is a highly interdisciplinary research environment that applies the principles of team science to combine such disparate fields as organic chemistry, enzyme engineering, droplet microfluidics, and X-ray crystallography.
Current research interests include:
- establishing new diagnostic platforms for disease detection & genotyping
- discovering therapeutic aptamers that can compete with traditional antibodies
- expanding the toolkit of enzymes available for synthetic biology
Chemical Synthesis
Chemistry students in the lab are working to develop new types of XNA monomers and investigating chemical strategies for improving the functional properties of XNA aptamers and catalysts.
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- A Scalable Synthesis of α-L-Threose Nucleic Acid Monomers
- A Gram-Scale HPLC-Free Synthesis of TNA Triphosphates Using an Iterative Phosphorylation Strategy
- P(V) Reagents for the Scalable Synthesis of Natural and Modified Nucleoside Triphosphates
Enzyme Engineering
Enzyme engineering students in the lab are using advanced microfluidics techniques to redesign the enzymes of life. We are primarily interested in establishing a broad toolkit of enzymes (e.g., polymerases, kinases, ligases, nucleases etc.) that the synthetic biology community can use to synthesize and modify genetic polymers with unique backbone structures (XNAs).
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- Elucidating the determinants of polymerase specificity by microfluidic-based deep mutational scanning
- Fluorescence-activated droplet sorting for single-cell directed evolution
- A General Strategy for Expanding Polymerase Function by Droplet Microfluidics
Therapeutic & Diagnostic Agents
Molecular biology students in the lab are evolving functional XNAs with specific target binding affinity (aptamers) and catalytic activity (XNAzymes). Functional XNAs isolated from these selections are basis for diagnostic and therapeutic applications.
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- Darwinian Evolution of an Alternative Genetic System Provides Support for TNA as an RNA Progenitor
- Synthesis and Evolution of a TNA Aptamer Bearing 7-Deaza-7-Substituted Guanosine Residues
- Evaluating TNA Stability Under Simulated Physiological Conditions
Structure Determination
Structural biology students in the laboratory are working to solve the X-ray crystal structures enzymes developed by the protein engineering team. Examining how these enzymes function at a molecular level is necessary for understanding their mechanism of action, which in turn will help guide the design of new XNA enzyme variants that function with enhanced activity.
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- Structural Basis for TNA Synthesis by an Engineered TNA Polymerase
- Crystal Structures of DNA Polymerase I Capture Novel Intermediates in the DNA Synthesis Pathway
- Crystal Structures of a Natural DNA Polymerase that Functions as an XNA Reverse Transcriptase
- Following Replicative DNA Synthesis by Time-Resolved X-ray Crystallography
