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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.

December 10, 2018
Carl V. Hamby, Ph.D.
Carl V. Hamby, Ph.D.

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.”