NYMC Researcher Recalls Past Collaboration with Nobel Laureate George P. Smith, Ph.D.
Dr. Smith was instrumental in NYMC's discovery of a new diagnostic peptide for Lyme disease.
In accepting the 2018 Nobel Prize in Chemistry, University of Missouri Professor George P. Smith, Ph.D., said science is like a web of ideas—intricately tied to the work that’s come before. It’s a statement that rings particularly true to Carl V. Hamby, Ph.D., associate professor of microbiology and immunology, and Gary P. Wormser, M.D., professor of medicine, microbiology and immunology, and pharmacology, and vice chair of medicine for research and development. “Dr. Smith was a co-recipient of the Nobel Prize in Chemistry for the development of phage-displayed peptide libraries, some of which he generously supplied and were instrumental in our discovery of a new diagnostic peptide for Lyme disease,” explains Dr. Hamby.
Describing the sequence of events that led to their discovery, Dr. Hamby says sometime in early 2005, he came across a report which detailed Dr. Smith’s work in identifying and sequencing peptides from his libraries that were specifically recognized by sera from Lyme disease patients. While Dr. Smith’s search of the TIGR protein sequence database did not yield any hits (therefore he and his team didn’t know if any of the peptides represented actual Lyme proteins), Dr. Hamby says he took the published sequences, using a different search strategy, he was able to find hits in the NCBI database, of which some were Borrelia (Lyme) proteins. “After finding this, I contacted George and he graciously sent several phage libraries plus 12 phage clones he had isolated and five purified peptides for me to screen with Lyme disease patient serum that I obtained from Dr. Wormser,” he says. “We were able to confirm George’s original findings and verify the similarity of some of the peptides to Lyme protein sequences or epitopes through protein database searches.” This ultimately led to the 2006 report by Drs. Hamby and Wormers: Use of Peptide Library Screening to Detect a Previously Unknown Linear Diagnostic Epitope: Proof of Principle by Use of Lyme Disease Sera.
While other diagnostic Lyme disease proteins had been previously discovered by different methods, their experiments and subsequent report were an important proof-of-principle of this “epitope discovery” method. “The approach of screening phage libraries displaying randomly generated peptides with serum from patients who had Lyme disease was successful in identifying a small number of peptides specifically recognized by Lyme disease patients,” he explains. “Upon sequencing those peptides and searching a protein sequence database we were able to discover the new Lyme epitopes the serum antibodies were reacting to. This gives us a new tool for finding peptides which can be used in diagnostic tests for Lyme disease.”