Accelerating Lead Optimization to Clinical Application Using Microscale Thermophoresis to Quantify Molecular Interactions

This project supports the purchase of a Monolith NT.115pico instrument for use in analyzing molecular interactions. UW–Madison has an urgent need for a general and sensitive method to detect and quantify molecular interactions, such as small molecule-protein, protein-protein, and oligonucleotide-protein binding affinities. Key applications include using the instrument to screen libraries of potentially bioactive compounds and as a quantitative binding assay in fundamental biological, biochemical, and biophysical research. The Monolith instrument uses a new technology based on the movement of biomolecules along a temperature gradient.

The Monolith instrument will support UW researchers as they conduct in-depth mechanistic studies of small molecule/drug target interactions, develop cancer immunotherapeutics, and partake in other related basic and translational research. The addition of the Monolith instrument to the campus capabilities will be critical to the research community since current instrumentation for binding assays on campus either requires a fairly significant amount of sample, or only provides quantitative information for a limited number of molecular interactions.  The instrument will be housed and run by trained staff at the UW Medicinal Chemistry Center (MCC) within the School of Pharmacy.

Principal Investigator

• Weiping Tang
  Professor of Pharmaceutical Sciences and Director of the UW Medicinal Chemistry Center
  

Co-Principal Investigator

• Michael Hoffmann
  Professor of Oncology and Director of the UWCCC Small Molecule Screening Facility
  

Co-Investigators

• John Feltenberger
  Associate Scientist in Pharmaceutical Sciences and Assistant Director of the UW Medicinal Chemistry Center
• Jennifer Golden
  Assistant Professor of Pharmaceutical Sciences and Associate Director of the UW Medicinal Chemistry Center

Collaborators

• Helen Blackwell
  Professor of Chemistry
• Timothy Bugni
  Associate Professor of Pharmaceutical Sciences
• John Denu
  Professor of Biomolecular Chemistry and Epigenetic Theme Leader at the Wisconsin Institute for Discovery 
• Katrina Forest
  Professor of Bacteriology
• Jiaoyang Jiang
  Assistant Professor of Pharmaceutical  Sciences
• James Keck
  Professor of Biomolecular Chemistry
• Glen Kwon
  Professor of Pharmaceutical Sciences
• Bo Liu
  Professor of Surgery
• Robert Lowery
  President and CEO of BellBrook Labs
• Douglas McNeel
  Professor of Medicine
• Andrew Mehle
  Assistant Professor of Medical Microbiology and Immunology
• Mario Otto
  Assistant Professor of Pediatrics
• Manish Patankar
  Professor of Obstetrics and Gynecology
• Paul Sondel
  Professor of Pediatrics
• Robert Striker
  Associate Professor of Medicine
• Michael Sussman
  Professor of Biochemistry and Director of the Biotechnology Center
• Douglas Weibel
  Professor of Biochemistry, Biomedical Engineering and Chemistry
• Yongna Xing
  Associate Professor of Oncology
• Wei Xu
  Professor of Oncology
• John Yin
  Professor of Chemical and Biological Engineering and Systems Biology Theme Leader at the Wisconsin Institute for Discovery