With NIH grant, Rowan professor studies the mysterious field of epigenetics

It’s common knowledge that the DNA passed down by parents is what determines a child’s genetic traits, down to hair and eye color. What Dr. Benjamin Carone, assistant professor in the Department of Molecular & Cellular Biosciences at Rowan University, is studying is somewhat different: not genetics, but epigenetics.

“In addition to DNA, parents pass on some information of their life experiences to kids,” Carone explained. “We tend to think of everything else other than DNA as a blank slate.” But these epigenetic traits, Carone said, can impact such significant factors as our children’s metabolism – and they are present prior to conception, in marks that appear in the father’s sperm.

Carone’s work in epigenetics has been awarded a $445,637 Academic Research Enhancement Award for Undergraduate-Focused Institution from the National Institutes of Health (NIH). With this funding, he and students in his lab will spend three years studying epigenetic marks in the sperm of mutant mice. Ultimately, what they hope to learn about the phenomenon extends well beyond reproduction in mice and could help human parents better time the start or growth of their own families.  

How a father’s diet could affect a child for a lifetime

The project will build on Carone’s prior work with mice, dating back to his postdoctoral research in 2010. This work established that the offspring of mice that are fed a low-protein diet develop metabolism that’s preprogrammed to store calories to help them survive in a starvation environment.

This altered metabolism isn’t caused by genetics – DNA – but instead by this life experience of dietary restriction, which impacted the bodies of the parent mice so significantly that it created “epigenetic marks” in the sperm of the fathers. Although the research used mice as models, there are compelling reasons to believe this phenomenon is true of humans as well.

“Having a poor diet around the time you want to have children can have lifelong effects on their metabolism,” Carone said. “We inherit more than what’s encoded in the genome.”

The challenges of studying epigenetics

“Over the past few decades, we have begun to see that these patterns of epigenetic inheritance emerge,” Carone said. “Now we are trying to understand how.”

Studying the mechanism by which the epigenetic marks develop and are passed on isn’t easy. For one thing, biological variances in people are too complex to identify the impact of epigenetics directly. Instead, Carone must first separate out a genetic change from an epigenetic change that’s present in sperm and then work to identify what that specific epigenetic mark’s effects on offspring are.

So far, there are three to five known types of modifications that can be passed on epigenetically. Carone is studying one specific subset of epigenetic mark that’s widely thought to be important but hasn’t been tested yet – chromatin, which plays a crucial role in the packaging of a genome inside a nucleus.

To do this challenging work, Carone is testing mutated mice, ones whose Ctcf gene has been deleted in a lab – marking the first time anyone has ever experimented with this mutation in spermatogenesis. In particular, Carone aims to learn precisely how the Ctcf gene – missing in these subjects – affects the chromosome architecture of sperm and whether the gene affects a normal embryo.

From mouse models to human outcomes 

“The work being done in this grant-funded project looks at what’s passed from parent to offspring and allows us to see which epigenetic marks cause altered states,” said Carone, a professor in the College of Science & Mathematics. “This will allow us to look more to the future and specifically parents’ behavior and its effects on children.”

Beyond diet, activities like smoking, drug use and potentially many more factors may also create epigenetic marks in sperm that cause children to inherit altered states in their biological makeup. Carone’s research is the next step to achieving a better understanding of this phenomenon and what its implications could be for humans.

“We want to understand the window of timing based on the level and degree of epigenetic marks,” Carone said. Once researchers learn more about the impact of these epigenetic marks, they can begin to narrow down how severely, and for how long, these factors affect reproduction.

Prospective fathers could use this knowledge to make more informed choices about making healthy lifestyle changes and how long they should wait after making these changes to conceive. “We can learn when best to have kids based on epigenetic reprogramming,” Carone said.  

Biomedical research at Rowan

“This project is part of a broader direction Rowan is going in, particularly in the field of biomedical research,” Carone said, referencing the University’s recent national recognition from the Carnegie Classification of Institutions of Higher Education as a Carnegie R2 classification – high research activity – institution.

“This project fits nicely with our school’s research profile,” said Carone. “The most exciting part about getting this grant is that it’s going to be a wonderful opportunity for undergraduate students to be doing absolute cutting-edge research in this growing field.”

Carone anticipates that a little over half of the students working in his lab – 10 undergraduate and two graduate students, in total – will join him in working on this particular project.