Mason researchers create a bioprospecting tool to hunt for Komodo dragon peptides
George Mason University researchers have developed a new bioprospecting tool to help them find promising Komodo dragon peptides that are germ-fighting powerhouses, according to new research in the Journal of Proteome Research.
The federal government’s Defense Threat Reduction Agency (DTRA) funded the research with a $7.57 million contract for the George Mason team to analyze peptides used by such “extreme animals” as Komodo dragons and American alligators to defend against infection, potentially leading to new drugs and strategies to fight infection and protect the warfighter from bacterial bioweapons.
The rampant spread of antibiotic resistance threatens our ability to treat what were once routine infections, and there is an urgent need for new antibiotics. These evolutionarily ancient reptiles could be a new source for antibiotics—they dine on carrion and live in bacteria-rich environments but rarely fall ill.
“Nature can provide great templates and models for the development of new drugs against these hard-to-kill bacteria,” said Monique van Hoek, a professor with Mason’s National Center for Biodefense and Infectious Diseases, who along with chemistry professor Barney Bishop founded Antimicrobial Discovery Research in the College of Science.
The team, led by Bishop, van Hoek, and Joel Schnur, needed to invent a new way to find potent peptides present in the blood of these animals, which could provide the basis for new antibiotics. These peptides are small proteins that contribute to the body’s first line of immune defense against infection.
With the help of Dr. Kent Vliet at the University of Florida and the St. Augustine Alligator Farm Zoological Park in Florida, the Mason researchers acquired samples of blood collected from a Komodo dragon named Tujah, who lives at the park. Their analysis of the dragon’s blood revealed a complex mixture of promising peptides, many of which were fragments of larger proteins.
Bishop’s approach to capturing and enriching peptides from plasma is a critical step in their peptide discovery process, and it has allowed the team to identify peptides that are undetectable using conventional methods.
Bishop and his team developed custom-made microparticles to isolate peptides with specific physical characteristics. The antimicrobial peptides they were after were small and combined both positively charged and “greasy” elements. So they created particles that were negatively charged to attract their positively charged peptide counterparts like magnets, and they contained “greasy” components in order to complement the “greasy” parts of the peptides.
Once caught by the microparticles, the peptides were analyzed using a mass spectrometer, which tells researchers the peptides’ sizes and molecular weights. The mass spectrometer also blasts apart the peptides to give researchers an in depth look at the molecular puzzle, allowing them to determine the amino acid sequences of the peptides.
“The people who like sequencing peptides in this way also seem to like puzzles,” Bishop said.
Van Hoek and Bishop developed a gated testing process to determine whether peptides met their specific performance criteria and identify those peptides that would move on for further evaluation. They looked for bacteria-killing peptides that inhibited bacterial growth. In this paper, the team describes applying their new approach to the identification and performance testing of peptides from the Komodo dragon, and they report a series of nested peptides that showed activity against the bacteria Pseudomonas aeruginosa and Staphylococcus aureus.
Along with the Komodo dragon and American alligators, the Mason team has also investigated other large reptiles, including salt-water crocodiles, Chinese alligators, and Siamese crocodiles. They’re on the hunt for more peptides with the potential to be developed into new antibiotics. The five-year grant wraps up in February.
Additional media coverage
Dr. Mikell Paige wins Early-Career Excellence Award
Dr. Mikell Paige has been chosen as the winner of the 2016 COS Dean’s Early-Career Excellence Award. The Early-Career Excellence Award is presented to a tenure-track faculty member in the College who has achieved notable success since January 2016 and has increased the profile of their Department and COS.
Dr. Paige will receive an honorarium and a plaque at the COS Holiday Reception tomorrow, December 9th, at 3pm in the Exploratory Hall Atrium. All are invited to attend and join in the festivities and the celebration.
Keep up the good work! CONGRATULATIONS!
Mason research could lead to new lung disease treatments
George Mason University researchers may have found a way to reverse the progression of chronic obstructive pulmonary disease (COPD), which is the third leading cause of death in the United States.
George Mason chemistry and biochemistry professor Mikell Paige received nearly $2.4 million in funding from the U.S. Department of Health and Human Services to find new treatments for COPD in collaboration with Y. Michael Shim, MD, at the University of Virginia Medical Center and Schroeder Noble, PhD, at the Walter Reed Army Institute of Research.
Current treatments for COPD, at best, improve patients’ quality of life but do not halt disease progression, said Paige.
“We hope this new anti-inflammatory pathway we are exploiting may be able to do more than relieve symptoms, and possibly reverse disease progression,” he said.
The researchers have discovered a new anti-inflammatory pathway that could help change the way the disease is treated. These pathways are part of the body’s immune response to disease or injury. This particular anti-inflammatory pathway involves the role of LTA4H, a protein coding gene, in clearing white blood cell, or neutrophilic, infiltration.
COPD is one of the top causes of disability and the third major cause of death in the United States, according to the National Heart, Lung, and Blood Institute. Sufferers experience symptoms ranging from a persistent cough and shortness of breath to wheezing and chest pain.
More than 11 million people in the United States have been diagnosed with COPD, but as many as 24 million people might have the disease and not know it, according to the American Lung Association.
Paige’s research could lead to new drugs that would need lower concentrations to be effective, require fewer doses per day, and be taken in tablet form. Moving research from the labs to patients is a priority at Mason.
The researchers are also trying to better understand the biological underpinnings for this pathway, which could potentially lead to further strategies for treating COPD or other inflammatory diseases.
Paige said discoveries made while working on this research grant could possibly reduce the incidence of lung cancer—a disease COPD sufferers are more likely to develop than non-sufferers.
This initial study is expected to be completed in the next four years.
Congratulations to Dr. Robin Couch, the recipient of the 2015 College of Science Dean’s Impact Award. The Impact Award is presented to a faculty member in the College who has achieved particular success, has made a notable impact, and brought recognition to the College during 2015.