The Truman Lab at UNC Charlotte has secured a new $2.1 million, five-year grant from the National Institutes of Health, awarded through the National Institute of General Medical Sciences’ Maximizing Investigators’ Research Award (MIRA) program, to advance research into how cells maintain protein health — a process central to diseases ranging from cancer to neurodegenerative disorders. The grant funds the project “Deciphering the Hsp70 chaperone code” and brings the lab’s active research funding to $6.05 million.
Bernadette Donovan-Merkert, Dean of the Klein College of Science, said: “This NIH award reflects both the scientific significance of Andrew Truman’s research with the team in the Truman Lab and his leadership in building a leading proteostasis research community at UNC Charlotte. By supporting long-term, curiosity-driven discovery, this grant will provide new insights into how cells maintain protein health and create opportunities for breakthroughs that could ultimately inform future therapies for devastating diseases. We are proud to see UNC Charlotte continue to lead in this important area of research.”
A Decade of Studying One of the Cell’s Most Essential Proteins
Founded in 2015, the Truman Lab studies proteostasis — the systems that keep proteins properly folded and functional — with a focus on Heat Shock Protein 70 (Hsp70), one of the cell’s most abundant and essential molecular chaperones. Andrew Truman is principal investigator, professor and associate chair for research in the Department of Biological Sciences, affiliate faculty in the School of Data Science, and leads the Charlotte Group for Proteostasis Research, which recently received sponsorship from NCBiotech.
The lab studies what it calls the “chaperone code” — a set of small chemical switches on Hsp70 that guide which tasks it performs, when it performs them, and which proteins it interacts with. “This five-year MIRA award is a major step forward for my group, giving us the long-term support and flexibility to decode and ultimately manipulate these signals,” Truman said. “We hope this work will reveal new ways to understand and treat diseases linked to damaged or misfolded proteins, including cancer and ALS.”
Mapping More Than a Hundred Chemical Switches
For decades, scientists studied Hsp70’s specificity through its expression levels, its family of isoforms, and the co-chaperone proteins that bind to it. Recent advances in proteomics have revealed a far more complex regulatory landscape: more than a hundred post-translational modifications have now been identified on Hsp70, a collection Truman’s team calls the Hsp70 chaperone code.
“The Hsp70 protein acts as a custodian of the cell, helping proteins to fold correctly, restoring those damaged by stress and removing proteins that cannot be fixed,” Truman said. “My group studies the chaperone code, a set of small chemical switches on Hsp70 that tell it which jobs to perform, when to perform them and which proteins to work with.” Over the past decade, the lab has shown that these modifications play key roles in heat stress response, cell cycle progression, and genome integrity. Similar regulatory patterns have been found on other chaperones, including Hsp90, but many Hsp70 modification sites remain unexplored.
What the Next Five Years Will Focus On
Over the next five years, the new R35 grant will allow the Truman Lab to map the stresses and enzymes that regulate most of these Hsp70 modifications in budding yeast and mammalian cells, and determine how they’re activated. Researchers will test how each modification affects Hsp70’s function both in vitro and inside cells, and will also investigate how modifications on Hsp70’s client proteins — described as the “client code” — influence chaperone interactions and protein behavior.
