Fred Hutchinson Cancer Center postdoctoral fellow Grant King, PhD, was named a 2023 Postdoctoral Fellow by the Damon Runyon Cancer Research Foundation. The four-year, $300,000 award will allow King to study how “extra-chromosomal” DNA, or DNA that breaks away from larger chromosomes, can persist long-term in cells.
“By studying basic questions, we can make the most profound insights that ultimately help human health,” said King, who is mentored by Fred Hutch evolutionary biologist Harmit Malik, PhD. “The Damon Runyon Fellowship supports that work.”
Pieces of DNA that reside outside chromosomes can help promote the evolution that cancer cells need to grow unchecked, spread and evade treatment. Understanding the biological processes that enable extra-chromosomal DNA to persist will help researchers looking for ways to hinder tumor evolution.
Damon Runyon’s postdoctoral fellowship is designed to encourage high-risk, high-reward cancer-related research and support early-stage researchers as they train to become independent leaders of their own research teams.
“Grant has embarked on an ambitious research agenda to shed light on a mysterious cellular mechanism that cancer cells use to thrive and thwart treatment,” Malik said. “His prowess in yeast genetics and cell biology, as well as his highly methodical style, are ideal fits for this project. I am extremely excited by what he might find and hopeful it will open new inroads into tackling some of the most difficult-to-treat cancers.”
“I’ve always liked microbes — I lose interest when you get too many cells,” King said.
Before arriving at Fred Hutch, King studied meiosis, a type of cell division that creates the sex cells that organisms from yeast to humans use to reproduce. (Human sex cells are eggs and sperm.) Like human cells, yeast cells house their DNA in the nucleus, a compartment separated from other parts of the cell. King studied how the nucleus remodels during the yeast meiosis, revealing a previously unknown strategy yeast use to eliminate age-related damage and ensure a rejuvenated next generation.
Single-celled organisms have a lot to teach us about how our own cells work, in ways that also provide insights about human health, King said.
“There’s still so much about cells that we don’t understand,” he said. “Yeast is streamlined: you can start with a simple unit to get a deeper understanding, and almost always those principles are present in other systems.”
Yeast and other species (like humans) that store their DNA in nuclei are called eukaryotes, and eukaryotes also like to keep their DNA organized in chromosomes. Free-floating DNA doesn’t obey the same biological rules as DNA housed on chromosomes, and can affect the health of eukaryotic cells, whether yeast or human.
His Damon Runyon award will allow King to outline the factors in yeast cells that interact with extra-chromosomal DNA.
“In the grand tree of life, yeast is actually closely related to human cells, and yeast cells are very easy to manipulate genetically,” King said.
He’ll learn about how cells work to quash extra-cellular DNA, and what factors sometimes enable it to persist, even as the cells grow and divide. Once King has worked out the principles in yeast, he’ll study human cells to see which ones still hold. Those that are evolutionarily conserved — meaning they’re present in both yeast and human cells — may be vulnerabilities that scientists can exploit to develop new cancer therapeutics, he said.
“The general principles of this process are not well known. I’m a firm believer in using basic systems to answer fundamental questions,” King said.
King is the fourth Damon Runyon fellow to be mentored by Malik. Former Malik Lab fellows Tera Levin, PhD, and Antoine Molaro, PhD, have established independent research groups, while Ching-Ho Chang, PhD, is currently a senior postdoc on Malik’s team.
Sabrina Richards, a staff writer at Fred Hutchinson Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a PhD in immunology from the University of Washington, an MA in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at email@example.com.