CVM researchers receive NIH-USDA grant to study mechanisms of chromosome instability and early pregnancy loss

A team of researchers from the University of Georgia College of Veterinary Medicine and the Regenerative Bioscience Center has received a five-year, dual-purpose grant of $1.65 million from the USDA and the NIH to study the effects of chromosomal abnormalities on early embryo development and to discover and validate novel markers of egg cell quality and development potential. This study stands to benefit knowledge of both human and animal development.

The team, led by Dr. Rabindranath De La Fuente, associate professor of physiology and pharmacology, will use the bovine embryo as a model to combine genome sequencing with state-of-the-art super-resolution imaging of chromosome structure. The first-of-its-kind approach will allow researchers to compare genome function with actual nanoscale visualization of the chromosomes as they segregate during cell division.

Benefiting both human and animal health

In human embryos, there is typically a loss rate of about 30% to 50% before implantation, Claudia Baumann, a research scientist in De La Fuente’s lab, explained. There are any number of reasons that embryos do not develop properly, but chromosomal instability is a leading factor.

In the cattle industry, the cost of embryo loss year over year is vast and can have a large economic impact.

The potential for an embryo to establish a healthy pregnancy is currently evaluated solely on the morphological appearance of the embryos, but such methods are not precise. The researchers are interested in developing new, non-invasive methods of assessing chromosome stability and developmental potential

“Making the link between embryo appearance, proper chromosomal function, and developmental potential is our goal. While it is generally true that the better-looking embryo exhibits a higher potential to carry a pregnancy to term, we want to know what critical factors functionally confer full developmental potential and ensure healthy offspring. Beauty truly is more than skin deep,” said Maria Viveiros, associate professor of physiology and pharmacology

A deeper look

This project marks the first time genomics (e.g., genome sequencing) will be combined with super-resolution analysis of mammalian chromosomes, allowing the researchers to view changes in chromosome organization through two completely different lenses.

Superresolution analysis of mammalian chromosomes (Submitted)

“We will be viewing the genome at two different scales. We will integrate a three-dimensional image reconstruction of the chromosomes at a level of resolution beyond the current optical diffraction limit and study functional interactions with genomic sequencing. We will see a true representation of how chromosomes are functionally organized and how they condense before segregation—and we will gain a better understanding of how and why chromosomes break when something goes wrong,” De La Fuente said.

The Athens-based team will partner with Dr. Lee Jones, associate professor of food animal health and management in Tifton, for this project, allowing them to see the effects of their research on the cattle industry firsthand. This project was developed with pilot research grants provided by institutions including the College of Veterinary Medicine and RBC as well as the Regenerative Engineering and Medicine initiative led by UGA, Emory University, and Georgia Tech.

“These pilot grants were essential in allowing us to collect sufficient preliminary data to assemble the grant application,” De La Fuente said. “This is a great example of how a small investment in pilot research grants can be transformed into a fully funded program.”

“The findings this team could make over the next five years might very well change the way we view human and cattle development, and the impacts reach even further—possibly shedding light on the effects of other chromosomal abnormalities like those causing Down syndrome and cancer. This research perfectly aligns with the college’s mission to better human and animal lives and might have massive impacts on the cattle industry worldwide,” Dr. Lisa K. Nolan, dean of the College of Veterinary Medicine, said.

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