A New Universe of Regulatory Microproteins

G. Burroughs Mider Lecture | Wednesday, September 10, 2025 | 3:00 to 4:00 p.m. ET

Gisela Therese Storz, Ph.D.

NIH Distinguished Investigator

NIH National Institute of Child Health and Human Development (NICHD)

storzg@mail.nih.gov

Website

Dr. Gisela Storz is the Associate Scientific Director of the Division of Molecular and Cellular Biology of NICHD. She received her Ph.D. from the University of California, Berkeley, and then carried out postdoctoral work at the National Cancer Institute and Harvard Medical School. For many years, a major focus of her group was the study of the bacterial and fungal responses to oxidative stress and redox-sensitive transcription factors. Her lab made the exciting discovery that the activity of the E. coli transcription factor OxyR is regulated by reversible disulfide bond formation, establishing a paradigm for redox-sensing proteins. As a result of the serendipitous detection of the peroxide-induced OxyS RNA, one of the first small, regulatory RNAs to be discovered, work in her lab shifted to the genome-wide identification of small RNAs. The pioneering characterization of many of these small RNAs revealed that they are integral to most regulatory circuits in bacteria. Recently, work in the Storz lab has extended to the detection and characterization of proteins of less than 50 amino acids, another class of molecules that is overlooked by traditional methods of investigation.

Summary

While much has been learned about the proteome in all organisms, a whole class of proteins—the smallest proteins—have been ignored due to challenges in their annotations and biochemical characterization. Thousands of these microproteins are now being discovered and shown to have regulatory roles in all organisms. By interacting with larger proteins, microproteins modulate the activities, subcellular localization and stabilities of these targets.

Learning objectives

• Appreciate the challenges in identifying the smallest proteins and why these have been missed.
• Understand how thousands of microproteins are being discovered through ribosome profiling and computational approaches.
• Learn about the regulatory roles of microproteins in modulating the activities, subcellular localization, and stabilities of transcription factors, enzymes, and transporters, likely in all organisms.