It takes a powerful microscope to view the tiny cellular structures known as primary cilia that are at the center of Inna Nechipurenko’s research.
“You can think of primary cilia as tiny antennae that project from the surface of nearly all cells in our bodies, and these antennae are absolutely essential for our cells to be able to communicate with each other and to collect information about their environment,” says Nechipurenko, an assistant professor in the Department of Biology and Biotechnology. “Their critical importance for human health is particularly highlighted by the fact that people who have any defects in the function of these structures suffer from devastating genetic disorders, for which there is no cure.”
Inna Nechipurenko
With nearly $564,000 in recently awarded funding, Nechipurenko is launching two projects that will investigate the genetic basis of primary cilia formation and function in nerve cells. These projects will provide the basic science foundation that is a necessary steppingstone for developing therapies.
The first project, funded with a three-year $363,984 grant from the National Institutes of Health, will determine how a gene called RIC-8 shapes primary cilia structure and function in neurons.
The second project, funded with a two-year $200,000 grant from the Charles H. Hood Foundation, will define the function of a human gene called GNAI1 in primary cilia assembly. The project will also use the microscopic worm C. elegans as a tool to rapidly and systematically determine how patients’ mutations in GNAI1 affect the gene’s function. GNAI1 is a known risk gene for neurodevelopmental disorders.
Both projects build on Nechipurenko’s research into the molecular machinery that is important for correct assembly and function of primary cilia in the nervous system.
“In the last 20 years or so, we came to appreciate how truly important cilia are for every aspect of human physiology,” Nechipurenko says. “We literally see, smell, and hear through cilia. We have also learned a great deal about molecules that are at the core of these structures, but the functions of cilia in the brain remain a mystery.”
Scientists first identified primary cilia in the 1800s but dismissed them as useless structures. That misconception changed after 2000 as researchers discovered the critical roles that cilia play in mediating cell-to-cell communication and linked cilia malfunction to a range of genetic disorders that include polycystic kidney disease, metabolic and cardiovascular diseases, and neurological conditions such as intellectual disability and autism spectrum disorder. More than 30 disorders and more than 150 genes have been linked to dysfunctional cilia.
“Although much progress has been made in the past 20 years to better understand all cellular roles that primary cilia play and why or how their dysfunction may lead to diseases, many questions remain,” Nechipurenko says. “We are particularly excited to begin asking how cilia functions intersect with other aspects of neuronal physiology, and why it is so detrimental to neurons if cilia do not function just right.”
