Sam Wilson Honored at Annual Mutagenesis Conference (Environmental Factor, October 2022)

It’s a testament to the impact that Sam Wilson, MD, has had in the field of environmental mutagenesis that scientists from around the world convened a day-long gathering to celebrate the impact of his research.

NIEHS was well represented at the 13th International Conference on Environmental Mutagens and the 53rd Annual Meeting of the Environmental Mutagenesis and Genomics Society (EMGS) August 27-September 1 in Ottawa, Canada. The institute was also a Diamond level sponsor of the conference.

“Sam was an outstanding researcher and was fundamental to the field of environmental mutagenesis,” said Scott Auerbach, Ph.D., of the NIEHS Division of Translational Toxicology. “He was one of the fathers of this field. There was much partying by Sam leading up to the meeting. He left a great legacy and influenced a tremendous number of trainees who went on to achieve great professional success.”

The field of environmental mutagenesis and genomics studies why and how environmental toxins or stressors cause cells in the body to develop DNA mutations. The field has come a long way in the 50 years since Wilson first donned his lab coat, largely due to advances in technology and increased scientific understanding.

“People are standing on the shoulders of giants like Sam as they develop the next generation of technologies to understand how chemicals contribute to disease,” Auerbach said.

continuation of work

Former NIEHS postdoc Joonas Jamsen, Ph.D.currently at the University of Arkansas for Medical Sciences (UAMS), presented research he conducted as one of Wilson’s mentees.

“I learned so much from him in terms of science and research, but also how to be a mentor and a good scientist,” Jämsén said of Wilson. (Photo courtesy of Steve McCaw / NIEHS)

Polymerase lambda, an enzyme involved in DNA repair, has historically been difficult to study. In Wilson’s lab, Jämsén helped develop a technique using time-lapse crystallography to visualize the structures that govern the function of polymerase lambda. By slowing down the activity of polymerase lambda, which normally works at nanosecond speeds, scientists were able to learn how the enzyme plays an important role in genome stability and instability.

“The results helped us understand how polymerases work and how DNA polymerase lambda contributes to environmental mutagenesis in DNA repair, as it is involved in DNA repair pathways that respond to environmental damage,” explained Jämsén.

Jämsén received the National Institutes of Health Pathway to Independence Award, which allowed him to set up his laboratory at UAMS.

“I owe everything to Sam’s help,” he said. “I hope to follow in Sam’s footsteps and uncover DNA repair mechanisms using a structural functional approach.”

Jämsén’s lab will take a closer look at DNA repair complexes and how polymerases work within them. Using a sophisticated technique called cryogenic electron microscopy, the lab will deconstruct DNA repair pathways to understand the role polymerases and mutagenesis play in oxidative stress and environmental impacts on human health.

Planning for borderline cases

Auerbach also presented at the conference and noted that Wilson’s research on mutagens helped lay the foundation for his own work in toxicoinformatics, a discipline that combines the science of toxicology with the tools of bioinformatics.

“One of the main types of chemical classes driving environmental risk are things that modify DNA — mutagens,” Auerbach said. “Once we understand how they do it and what patterns they produce, we can follow them from an epidemiological perspective. We can trace their mutation signatures.”

“The beauty is the impact of someone who was such a smart scientist and such a nice person that he will shine for years to come,” Kunkel said of the legacy Wilson leaves behind. (Photo courtesy of Steve McCaw / NIEHS)

Auerbach measures mutagenic changes at the molecular level with the aim of identifying potentially harmful exposures to certain chemicals or drugs long before these problems manifest themselves at the biological level in the form of tumors and diseases.

Occasionally, chemical tests or drug trials show no detectable biological effect in participants, leading to greenlighting of substances believed to be safe that are actually unsafe. Thalidomide, the morning sickness drug given to pregnant women in the 1950s and 1960s that caused severe birth defects, is an example that Auerbach cites as a borderline case.

Auerbach noted that new strategies known as error-corrected sequencing could help researchers find such edge cases and identify mutational signatures more quickly. The technique allows scientists to detect mutations in individual cells before they spread and cause full-blown cancer.

“The idea is that the doctor could take a few blood or tissue samples each year, take error-corrected samples, and look for unique patterns,” Auerbach said. “Everyone thinks this technology has a lot of promise, not only for toxicology, but also for cancer prevention.”

Citation: Jämsén JA, Shock DD, Wilson SH. 2022. Observing correct and incorrect nucleotide insertion captures hidden checkpoints of polymerase fidelity. Nat Commun 13(1):3193.

(Kelley Christensen is a contract writer and editor for the NIEHS Office of Communications and Public Liaison.)