A research team at Boston University School of Medicine (BUSM) has identified an important and novel connection between genes that guide the body plan of the common fruit fly and nerve cells in humans that underlie disorders such as epilepsy and anxiety. Results from this study, conducted by faculty within the department of pharmacology and experimental therapeutics at BUSM, were published online in the journal BMC Pharmacology and Toxicology.
“It is well known that humans and Drosophila melanogaster hold many neurological properties in common, with almost three-fourths of genes related to disease in humans having a similar counterpart in the fruit fly,” said David H. Farb, PhD, director of the university-wide National Institute of General Medical Sciences (NIGMS) pre-doctoral training program in Biomolecular Pharmacology and chair of the Department of Pharmacology & Experimental Therapeutics at Boston University and BUSM. “What is surprising in our study is the seemingly disparate nature of the human and fruit fly counterparts; we found that a specific inhibitory receptor in the human brain can be modulated by a protein that governs homeotic, or ‘body plan’, genes in the fruit fly.”
This receptor, known as the Type-A GABA receptor, is normally activated by the neurotransmitter GABA in the central nervous system and serves as a brake on transmission of electrical signals in the brain. A malfunction in this inhibitory system can produce a range of neurological disorders, including epilepsy, a condition in which uncontrolled surges of electrical activity in the brain produce muscular seizures. Nearly 3 million people in the U.S. have epilepsy, and almost 200,000 new cases are diagnosed each year.
Farb and Shelley J. Russek, PhD, director of BU and BUSM’s Graduate Program for Neuroscience, showed that a fruit fly protein, PHF1b, increases the expression of the GABA receptor by binding to a unique genetic “start site” in humans known as β1-INR. In the fruit fly, PHF1b is a member of a group of Polycomb proteins that guide how the fly’s body will develop (for example, by specifying placement of legs, wings and antennae). Why PHF1b would stimulate the genetic expression of neural receptors in humans remains a mystery, particularly given that Polycomb group proteins maintain repression of homeotic genes in fruit flies. Continuing research at BUSM may shed further light on the “electric connection” between humans and fruit flies, with the hope of one day developing novel treatments for epilepsy and other GABA-related disorders such as anxiety.
Research team: Shamol Saha, Yinghui Hu, Stella C. Martin, Sabita Bandyopadhyay, Shelley J. Russek, David H. Farb.
Polycomblike protein PHF1b: a transcriptional sensor for GABA receptor activity.
Submitted by David H. Farb, PhD.