Dr. Christophe Herman, professor of molecular and human genetics and molecular virology and microbiology at Baylor College of Medicine, has been awarded the National Institutes of Health Director’s Pioneer Award. The award supports scientists with outstanding records of creativity pursuing new research directions to develop pioneering approaches to major challenges in science. The $3.5 million award will fund his work to overcome growing resistance to antibiotics and to develop a genetically engineered antimicrobial platform.
“The discovery of antibiotics has saved many millions of people. We all take antibiotics. The problem is that we are abusing the system. Bacteria are very smart and they can very quickly evolve and become resistant,” said Herman, a member of the Dan L Duncan Comprehensive Cancer Center at Baylor. “I wondered, could you hijack the function bacteria use to protect themselves from invading viruses and evolve resistance to do the opposite and kill them?”
Herman will work to create a non-antibiotic platform to treat bacterial infections by engineering antimicrobial bacteria to attack pathogens. He will harness bacterial sex, the process that drives antibiotic resistance, to deliver toxic CRISPR nucleases to selectively destroy pathogenic bacterial DNA. The main bottleneck is to tame bacterial sex to deliver the deadly CRISPR toxin and make sure the system is contained to infected people. He will develop a universal method to transfer this engineered DNA from a harmless bacterial carrier to pathogenic bacteria and engineer a way to control the curing-bacteria, preventing it from spreading to the wild.
This new antimicrobial method, called the Cas system, will provide another benefit over antibiotics. Herman said his strategy would be more selective in the bacteria it kills. The Cas system can target specific genetic variations found only in pathogens, leading the genetically engineered bacteria to seek out bad bacteria, and leave the helpful bacteria alone.
“Right now when you take antibiotics, it kills everything. It’s not specific. You kill bad bacteria but you also kill the good ones. That’s a problem,” Herman said. “A lot of bacteria are there to protect us. This new method may be better because it can specifically target bad bacteria.”
Herman’s previous work has focused on changes in heritable gene expression caused by transcription errors. It is well established that changes in DNA can alter the phenotype. His research has shown that mistakes in mRNA transcription in cells can affect protein production and cellular programs, thereby impacting phenotypic inheritance for generations.
“Dr. Herman’s work is not only innovative, it has the potential to address one of the greatest health challenges of our work, that of infection and antibiotic resistance. Receiving a Pioneer Award is one of the highest recognition by the NIH,” said Dr. Brendan Lee, professor and chair of molecular and human genetics at Baylor.
The Pioneer Award is part of the NIH Common Fund’s High-Risk, High-Reward Research Program, which supports ideas with potential for great impact in biomedical research. Program applicants are encouraged to think outside the box and to pursue creative, trailblazing ideas in any area of research relevant to the NIH mission. This year, the NIH awarded 93 High-Risk, High-Reward grants, totaling approximately $267 million over the next five years, pending available funds. Herman’s work will be funded by NIH grant (DP1 AI152073).