(Boston)—Stefan Isaac, PhD, assistant professor of biochemistry and cell biology at Boston University Chobanian & Avedisian School of Medicine, has received a $2.1M Maximizing Investigators' Research Award (MIRA) (R35) from the NIH National Institute of General Medical Sciences (NIGMS) to fund his five-year project “Regulation of mitochondrial DNA packaging and gene expression.”
Mitochondrial disorders are caused by defects in mitochondria, the energy-producing structures found in nearly all cells of the body. Because muscle and nerve cells have especially high energy needs, muscular and neurological problems are common features of mitochondrial disorders. Other common symptoms include impaired vision, hearing loss, abnormal heartbeat (cardiac arrhythmia), diabetes, and stunted growth.
Isaac’s lab studies how mitochondrial DNA packaging, gene expression, and DNA replication are regulated and the mechanisms that govern the activity of this genome. His lab uses a multidisciplinary approach, combining genomics and bioinformatics, in vitro biochemistry and molecular and cell biology to understand these biological processes. Over the next five years, he will develop and apply novel sequencing-based assays to reveal how cells regulate their energy production through mitochondrial DNA (mtDNA) packaging, expression, and replication.
“Single-molecule sequencing is giving us a view of mitochondrial DNA that simply wasn’t possible before,” says Isaac. “We’re using that to ask fundamental questions about how this genome is packaged, expressed, and replicated, and to uncover the basic rules governing how cells control their energy supply and what goes wrong in mitochondrial disease.”
Isaac received his PhD at the University of California, San Francisco, in the laboratory of Geeta Narlikar, PhD, studying how HP1 proteins play varied roles in heterochromatin establishment and maintenance. He was a postdoctoral fellow with Stirling Churchman, PhD, at Harvard Medical School, where he developed mtFiber-seq, an approach that maps protein occupancy across individual mitochondrial DNA molecules at nucleotide resolution.
The goal of MIRA is to increase the efficiency of NIGMS funding by providing investigators with greater stability and flexibility, thereby enhancing scientific productivity and the potential for important breakthroughs.