Tuesday December 12, 2017

Early Eye Development

University of Dayton biologist Amit Singh is studying early eye development in fruit flies to understand the molecular basis of retinal disease and birth defects in the human eye under a new $439,499 grant from the National Institutes of Health.

 

Singh, associate professor of biology and interim director of the Center for Tissue Regeneration and Engineering at Dayton (TREND), is using the fruit fly eye model to determine how genes regulate the process of transforming a single layer of cells into a three-dimensional organ.

“If this basic process of three-dimensionality is impaired, then there are organs that are half-formed or not formed at all,” Singh said. “People are born without eyes or they have defects in their eye that affect their vision.”

In 2010, Singh received a $218,250 NIH grant to research the genetic circuitry involved in regulating eye cell growth and patterning.

Under that grant, Singh’s lab in the TREND Center identified genes responsible for the three-dimensional patterning process along the dorso-ventral axis — one of three anatomical axes to which cells are assigned during early eye patterning. His research successfully identified how the boundary between the eye and the head structure is formed. It also identified a transcription factor, which controls gene expression, that could play a role in where the eye is placed on the head.

“What we are trying to understand now is how these genes control this process of delineating three-dimensional structure from a monolayer organ in the earliest stages of development,” he said.

His lab will also test the role of the transcription factor’s human equivalent, which is involved in cancer growth and metastasis.

“Understanding how this transcription factor works will not only have implications on birth defects of the eye, but it will also help us understand how it is involved in the growth of cancer,” Singh said. “These are two major things that might emerge from these studies.”

The project is funded through July 2020 and will employ a post-doctoral researcher, two graduate students — one full-time and one part-time — and three undergraduate student researchers.

In addition to early eye development, Singh’s lab also focuses on early detection of Alzheimer’s, an incurable disease that afflicts an estimated 5.5 million Americans. In June, he was awarded a University of Dayton STEM Catalyst grant to identify targets and drug-like molecules for the treatment of Alzheimer’s disease by studying the effects of amyloid protein — a potential driver of Alzheimer’s — using the fruit fly's eye as a model.

Scientists use fruit flies to model human diseases at the cellular and molecular levels because they have similar genetic traits to those of humans. The fly’s entire life cycle is just 12 days, which allows researchers to study the transmission of hereditary traits and investigate the genetics of disease across at least 24 generations in a year.

“Flies share genetic machinery with humans, so whatever we study in flies can be extrapolated to higher organisms, including humans,” Singh said.

Five Nobel Prizes have been awarded to science originating from fruit fly research, including the American research team that won the 2017 Nobel Prize in Physiology or Medicine. They were honored for isolating a gene that controls the normal daily biological rhythm, using fruit flies as a model.

“Amit is a top researcher in early eye development and disease, and is highly respected by his peers both at the University and in his field,” said Mark Nielsen, professor and chair of the department of biology. “His significant NIH awards reflect both the value and importance of his research.”

Singh, who also serves as director of the graduate program in biology, joined the faculty in 2007. He holds a bachelor’s degree from the Government Degree College Nahan, H.P. University, India, and a master’s and doctorate, both from Devi Ahilya University, Indore, India.

More than 20 researchers from six academic departments and the University of Dayton Research Institute participate in TREND Center research. Center investigators maintain nearly $5 million in research contracts and grants, and have compiled more than 500 peer-reviewed articles.

For more information, please visit the TREND Center’s website.

- Dave Larsen, communication coordinator, College of Arts and Sciences

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