Genetics professor receives two NIH awards

University of Georgia researcher Pengpeng Bi received a pair of National Institutes of Health grants in September: a Maximizing Investigators' Research Award (MIRA, 2022–2027) and an Exploratory/Developmental Research Grant Award (R21, 2022–2024). The $2.3 million awards will support efforts to uncover the molecular mechanism of human muscle development and homeostasis.

The MIRA is a funding mechanism to provide support for a program of research in an early-stage investigator’s laboratory that falls within the mission of the National Institute of General Medical Sciences, which funds basic research that increases our understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment, and prevention.

"We are deeply fascinated by skeletal muscles, the most abundant, beautiful, and highly organized tissue in our body that plays the fundamental roles for life and the homeostasis of many other organs" said Bi, an assistant professor at the Center for Molecular and Medicine, and the Franklin College of Arts and Sciences department of genetics. “The basic cellular composition of skeletal muscle is known as myofiber, each containing 1,000s of nuclei because of cell fusion. My lab strives to understand the challenges and opportunities that the cell fusion – a deeply conserved mechanism – brings to the formation, repair, and function of the human muscles.”

The R21 award will support the discovery of unknown genetic factors that control muscle cell fusion, thereby providing fundamental knowledge required to enhance human muscle development and function in patients where cell fusion is defective.

The work will build on recent findings published by Bi’s lab, including a 2021 study in PLOS Genetics and a 2020 study in Science Advances. These studies reported the key roles and crucial regulations of two membrane proteins during human muscle cell fusion.

“Our rigorous genetic tests clearly point to the existence of additional unknown factors required for muscle fusion, and thus served as a strong basis for the proposal.” Bi said. “With this award, my group will deploy the newest high-throughput genome editing technology to uncover and describe these factors.”

The MIRA award will allow the Bi lab to investigate the basic genetic mechanism operating in the gigantic volumes of the myofibers in a spatially defined manner. State-of-art genomics and imaging technologies will for the first time allow the dissection of several significant questions concerning how the complex myofiber system is formed and controlled. This proposal also capitalizes on a key myofiber engineering strategy inspired by a research project the Bi lab published in in Science Advances in September. The new paper reported how muscle fusion, which was instrumental for the adaptive radiation of vertebrates, has evolved.

“Through this evolutionary developmental biology project, we discovered a set of unique forms of muscle fusion proteins from various animal groups, providing a key solution to precisely engineer the cell fusion described in the MIRA proposal.” Bi said.

“UGA is especially strong in organism development and genomics, with many excellent faculty members working on these areas.” Bi said. “This provides the fertile ground for multidisciplinary collaborations such that we can create a virtuous cycle of innovation and discovery over the course of the NIH awards. We anticipate that the knowledge and techniques will benefit the greater biological community, including genetics, cell biologists, and developmental biologists on the UGA campus, and provide the basic frameworks for therapeutics to treat muscle diseases.”

Image: an isolated single myofiber isolated from mouse and stained to show nucleus (cyan) and the sarcomere (red) courtesy of the Bi lab.